RSS 2.0 Feed

» Welcome Guest Log In :: Register

Pages: (2) < [1] 2 >   
  Topic: Evolution of prokaryote flagella, Links to discussions, webpages, refs< Next Oldest | Next Newest >  

Posts: 319
Joined: May 2002

(Permalink) Posted: Dec. 17 2002,20:39   

Some articles on virulence functions for:

(1) Type III secretion systems
Cornelis GR, and Frédérique Van Gijsegem. Assembly and function of Type III secretory systems. Annual Reviews Microbiology. 2000. 54:735-774.

In the "T3SS are not good for you" theme:


For a rather long period, it was assumed that gram-negative bacteria do not "secrete" proteins into their environment but only export proteins in their strategic periplasm. However, research in the last two decades has revealed that gram-negative bacteria do indeed transfer proteins across their sophisticated outer membrane, and they do this by a variety of systems that are now classified into four major types and several minor ones. Type I, exemplified by the hemolysin secretion system of Escherichia coli, is a rather simple exporter that is based on only three proteins, one of which belongs to the ABC transporters. Type II is a very complex apparatus that extends the general secretory pathway and transfers fully folded enzymes or toxins from the periplasm to the extracellular medium, across the outer membrane. Type IV, another complex system that transfers pertussis toxin among others, is related to the apparatus of Agrobacterium spp. that transfers DNA to plant cells. Finally, type III, the subject of this review, is a sophisticated apparatus that couples secretion with pathogenesis.

In bacteria that are pathogenic for animals, type III secretion systems allow extracellular bacteria adhering to the surface of a host cell to inject specialized proteins across the plasma membrane. This system probably also allows bacteria residing in vacuoles to inject proteins across the vacuolar membrane. The injected proteins subvert the functioning of the aggressed cell or destroy its communications, favoring the entry or survival of the invading bacteria. Type III is thus not a secretion apparatus in the strict sense of the term but rather a complex weapon for close combat. It contributes to a number of totally different animal diseases with a variety of symptoms and severities, from fatal septicemia to mild diarrhea and from fulgurant diarrhea to chronic infection of the lung. Type III secretion has been extensively studied in Yersinia spp. (reviewed in 25), in Salmonella spp. (reviewed in 47), in Shigella spp. (reviewed in 138), and in enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) (40, 50, 72). It has also been described in Pseudomonas aeruginosa (TL Yahr & DW Frank, Genbank PAU56077), Chlamydia trachomatis and Chlamydia pneumoniae (73A), Bordetella bronchiseptica (MH Yuk, ET Harvill, JF Miller, Genbank AFO49488), Bordetella pertussis (78A) and in Burkholderia pseudomallei (The Sanger Center, Cambridge, UK). It is surprising that Salmonella typhimurium and Yersinia spp. have not only one type III system but two (61, 104; S Carlson & DE Pierson, Genbank AFO055744; The Sanger Center, Cambridge, UK), presumably playing their role at different stages of the infection (Figure 1).

Type III systems in animal pathogens. Illustrated are the various bacterial pathogens endowed with type III secretion, injecting effectors into the cytosol of a eukaryotic target cell. See Table 3 for references.

(bold added)

(2) In the "Flagella aren't necessarily good for you either" category:

Giron JA, Torres AG, Freer E, Kaper JB. The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial cells. Molecular Microbiology 2002 Apr;44(2):361-79


Posts: 319
Joined: May 2002

(Permalink) Posted: Dec. 17 2002,21:06   

In the "nonmotile appendages can have a dispersal-related function despite being nonmotile" category:


Knutton S, Shaw RK, Anantha RP, Donnenberg MS, Zorgani AA. The type IV bundle-forming pilus of enteropathogenic Escherichia coli undergoes dramatic alterations in structure associated with bacterial adherence, aggregation and dispersal.  Mol Microbiol 1999 Aug;33(3):499-509
BFP, a plasmid-encoded type IV bundle-forming pilus produced by enteropathogenic Escherichia coli (EPEC), has recently been shown to be associated with the aggregation of bacteria and dispersal of bacteria from bacterial microcolonies. In standard 3 h HEp-2 cell assays, EPEC adhere in localized microcolonies; after 6 h, bacterial microcolonies are no longer present, indicating that bacterial aggregation and dispersal occurs in vitro during EPEC adhesion to cultured epithelial cells. To examine the role of BFP in EPEC aggregation and dispersal, we examined HEp-2 cell adhesion of strain E2348/69 and defined E2348/69 mutants by immunofluorescence and immunoelectron microscopy. BFP was expressed initially as approximately 40 nm diameter pilus bundles that promoted bacteria-bacteria interaction and microcolony formation. BFP subsequently underwent a striking alteration in structural organization with the formation of much longer and thicker ( approximately 100 nm diameter) pilus bundles, which frequently aggregated laterally to form even thicker bundles often arranged in a loose three-dimensional network; EPEC dispersal from bacterial microcolonies was associated with this transformation of BFP from thin to thick bundles. Bacterial dispersal and transformation of BFP from thin to thick bundles did not occur with a bfpF mutant of strain E2348/69. It is concluded that BFP promotes both the formation and the dispersal of EPEC microcolonies, that the dispersal phase requires BfpF and that dispersal is associated with dramatic alterations in the structure of BFP bundles.


As dispersal of bacteria from microcolonies occurred between 3 h and 6 h, we examined cells at intermediate times in order to follow the dispersal process and any associated change in BFP morphology. At 4 h, by both immunofluorescence (Fig. 6A, arrow) and scanning electron microscopy (Fig. 7A, arrows), one could start to see the formation of thick BFP bundles within some bacterial microcolonies and, by scanning electron microscopy, bacteria appeared to have been lost from regions of the microcolony in which thick BFP bundles had formed (Fig. 7A). At 5 h, significant dispersal of bacteria from many microcolonies had occurred, although this varied from colony to colony.

Fig. 7. Scanning electron micrographs of HEp-2 cells infected with EPEC strain CVD206 for 4 h (A), 5 h (B) and 6 h © showing stages in bacterial dispersal. After 4 h, thick BFP bundles are forming within this bacterial microcolony, and bacteria look as though they may have been lost from these regions of the microcolony (A, arrows). After 5 h, dispersal of bacteria from some microcolonies is almost complete, and only a few small bacterial aggregates remain attached to thick BFP bundles (B, arrows); in contrast, there is no evidence of BFP transformation or bacterial dispersal in the microcolony seen on the right (B, asterisk). After 6 h, bacterial dispersal is virtually complete; one of the few remaining bacteria from this microcolony is anchored to the thick BFP bundles by thin bundles (C, arrows). Scale bars: A, 1 m; B, 2 m; C, 0.5 m.


BfpF and bacterial dispersal

BfpF has been shown to be required for the dispersal of EPEC from bacterial microcolonies (Bieber et al., 1998). We therefore examined a bfpF mutant of E2348/69 in order to determine whether the observed morphological transformation of BFP was affected by this component of the BFP operon. In 3 h assays, we confirmed previous observations that a mutation in bfpF resulted in increased localized adhesion and that bfpF mutants are hyperpiliated compared with the wild-type strain. Furthermore, the mutation did not affect the ability of this strain to produce A/E lesions. Other than the size of microcolonies, this phenotype showed no alteration after 6 h (Fig. 8); bacteria remained hyperpiliated (Fig. 8A), adherent bacteria produced A/E lesions (Fig. 8C and D), but there was no transformation of thin BFP bundles to thick bundles (Fig. 8A and B) and no dispersal of bacteria from microcolonies (Fig. 8A, B and D).

The original description of BFP defined a role in bacteria-bacteria interaction and microcolony formation (Girón et al., 1991); recently, it has been shown that BFP also promotes dispersal of bacteria from aggregates (Bieber et al., 1998). Bieber et al. (1998) ended their paper by suggesting that 'to dissociate from the aggregate, bacteria would need to shed or distangle their pilus filaments from each other, a process that may require BfpF-mediated, energy dependent pilus retraction or a conformational change in the pilus quaternary structure'. This study, which has now demonstrated that EPEC aggregation and dispersal occurs in vitro during infection of cultured epithelial cells, suggests that the latter may be the case and that BFP undergoes a dramatic BfpF-dependent change in quaternary structure, the consequences of which are (i) a change from a thin to a thicker BFP bundle structure; (ii) disruption of bacteria-bacteria interactions; and (iii) dispersal of EPEC from bacterial microcolonies. The advantage to the organism of such a mechanism is that dispersal of bacteria primed to produce A/E lesions would be expected to lead to infection of new epithelial sites within the small bowel and, therefore, to a more efficient colonization of the gut. It has been known for some time that EAF plasmids are important in EPEC pathogenicity; BFP, by promoting more efficient colonization, is one likely reason why typical EPEC, which possess EAF plasmids, are more virulent than atypical EPEC, which lack EAF plasmids (Levine et al., 1985), and also more virulent than EPEC BfpF mutants, which lack the ability to disperse from microcolonies (Bieber et al., 1998).

Although we suggest a causal relationship between BfpF function, transformation of BFP morphology and bacterial dispersal, the data do not, in fact, demonstrate such a relationship, and so we cannot rule out the possibility that the converse is true, namely that BfpF is involved in other events that promote dispersal of bacteria from microcolonies, which leads, in turn, to the formation of the thick BFP bundles. BFP are very hydrophobic pili and, as bacteria disperse from an aggregate, it could be that the thin BFP filaments become more accessible to each other and are able to associate to form the thick BFP bundles.

In addition to playing a role in bacterial dispersal, an adhesive role for BFP has also been suggested (Girón et al., 1991). While the aim of this study was to examine the role of BFP in bacterial aggregation and dispersal, some of the observations have relevance to the possible role of BFP in cell adhesion. For example, the data suggest that BFP may be involved in initial EPEC adhesion, but that intimin-mediated intimate attachment is required for subsequent adhesive events. Also, the presence of cell-associated BFP after dispersal of all CVD206 bacteria after 6 h demonstrates that this form of BFP can adhere to the surface of HEp-2 cells. However, the role of BFP in EPEC adhesion to cultured and intestinal epithelial cells is the subject of a separate study to be published elsewhere (S. Knutton et al., manuscript in preparation).

[well, "nonmotility" is debatable, but this doesn't appear to be directional movement, i.e. swimming or crawling]

This study confirmed a role for BfpF in microcolony dispersal (Bieber et al., 1998) and showed that this protein, while not required for thin BFP bundle assembly, is involved either directly or indirectly in transformation from thin to thick BFP bundles. Based on the similarity between BfpF and PilT, the putative nucleotide-binding protein of P. aeruginosa, it has been proposed that BFP may play an analogous role to that proposed for PilT in type IV pilus function, namely as an energy source for the retraction of BFP (Anantha et al., 1998). The proposed function of PilT is based on electron microscopic studies of the distribution of antibody and bacteriophage binding to pili from wild-type and mutant P. aeruginosa strains (Bradley, 1974). The mutant used for these studies was subsequently found to have a mutation in pilT, which is also required for twitching motility (Whitchurch et al., 1991). As proteins in the PilT family are proposed to reside in the cytoplasm, our finding that BfpF appears to have a profound effect on the quaternary structure of BFP outside of the bacteria is surprising. However, as BFP has a marked propensity to intertwine in rope-like bundles, it is possible that retraction of individual pili within a bundle mediated by BfpF leads to thickening of the bundle in much the same way as pulling on an individual fibre leads to thickening of a twine. Thus, our study provides additional evidence that type IV pili such as BFP are not fixed structures, but are capable of dynamic alterations that influence bacterial adherence and pathogenesis.


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 01 2003,18:29   

In the "another whole kind of motility" category:


Molecular Microbiology
Volume 47 Issue 3 Page 657  - February 2003
Motility modes of Spiroplasma melliferum BC3: a helical, wall-less bacterium driven by a linear motor
Rami Gilad1, Asher Porat2 and Shlomo Trachtenberg1*


Spiroplasma are members of the Mollicutes (Mycoplasma, Acholeplasma and Spiroplasma) - the simplest, minimal, free-living and self-replicating forms of life. The mollicutes are unique among bacteria in completely lacking cell walls and flagella and in having an internal, contractile cytoskeleton, which also functions as a linear motor. Spiroplasma are helical, chemotactic and viscotactic active swimmers. The Spiroplasmal cytoskeleton is a flat ribbon composed of seven pairs of fibrils. The ribbon is attached to the inner side of the cell membrane along its innermost (shortest) helical line. The cell's geometry and dynamic helical parameters, and consequently motility, can be controlled by changing differentially and in a co-ordinated manner, the length of the fibrils. We identified several consistent modes of cell movements and motility originating, most likely, as a result of co-operative or local molecular switching of fibrils: (i) regular extension and contraction within the limits of helical symmetry (this mode also includes straightening, beyond what is allowed by helical symmetry, and reversible change of helical sense); (ii) spontaneous and random change of helical sense originating at random sites along the cell (these changes propagate along the cell in either direction and hand switching is completed within 0.08 second); (iii) forming a deformation on one of the helical turns and propagating it along the cell (these helical deformations may travel along the cell at a speed of up to 40 µm s1); (iv) random bending, flexing and twitching (equivalent to tumbling). In standard medium (viscosity = 1.147 centipoise) the cells run at 1.5 µm s1, have a Reynolds number of 3.5  106 and consume 30 ATP molecules s1. Running velocity, duration, persistence and efficiency increase with viscosity upon adding ficoll, dextran and methylcellulose to standard media. Relative force measurements using optical tweezers confirm these findings.

If all Mycoplasma are derived parasites of eukaryotes (?) then presumably this motility system is of relatively late origin.


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 07 2003,01:12   

Although the basics of how the eubacterial flagellum works are reasonably well-known

(see Howard Berg's article in Physics Today, Motile Behavior of Bacteria for a good introduction) remaining mystery surrounds the exact mechanism by which the flow of H+ powers rotary motion.  


Here is Berg's figure of the flagellum:

H+, aka protons, hydrogen ions, or "acid", flow from the inter-membrane space (where ATPases, photosynthesis, and other processes store them at high concentration) into the cell (down, in Berg's figure) where they are at lower concentration.

Somehow this energy is converted into motion of the cell.  A number of diverse models have been proposed for how exactly this might occur.  Mike Gene briefly reviews a couple of them in his argument for the nonevolution of the flagellum here.

He includes a figure derived from a paper on the question of motor mechanism:

The grey round thing represents the FliG protein (the part of the C-ring that interacts with the motor proteins, MotA and MotB) and the pinkish things with the H+ or Na+ flowing through them represent the MotAB complex.

[WARNING: beginning marginally informed speculation section.  Treat as one would treat a mathematical "conjecture" -- or rather just a conjecture, I'm sure math is more formal about such things]

Perhaps we can imagine two main classes of models:

1) Those in which the H+ flow plays a *direct* role in rotating the flagellum (e.g., the "proton turbine model" in the left of the figure).  This is, BTW, an appealingly simple model for motor operation: the protons just flow on through and the charges interact with the diagonally-positioned charges on the C-ring, sort of like wind blowing on a windmill.  Presumably a conformation change in FliC could reverse the diagonal direction and presto, rotation in the opposite direction.

2) Those in which the H+ flow causes some conformation (shape) change in the MotAB complex, which then interacts to "push" (speaking very basically; could be a Brownian ratchet for instance) on the C-ring.  How a conformation change in FliC would produce reverse rotation on this model is obscure to me, although I'm sure there's a way.

Based on the idea that MotAB had flagellum-independent origins in the form of proteins homolgous to ExbB (and ExbD IIRC), can we make any guess as to which of these might be more likely?

The difficulty with #1 would appear to be that both the proto-FliC and proto-ExbB would have to be at least crudely adapted to accepting proton flow.

It seems to me that #2 might be more likely if MotAB evolved from ExbB-like ion channels and if those channels functioned by conducting H+ through them and using the resulting conformation changes to perform work elsewhere at a distance.  The proto-MotB (already adapted for performing H+-powered work on some other protein) might be the only thing that would have to mutate in order to get some crude purchase on the proto-FliC (the base of a transport system, but that's another part of the story).

Anyway, the basic idea is that it would be cool, for instance, if one could predict which functional model to prefer based on an evolutionary based on homology with ExbB...

All of this depends upon further understanding of how the Exb complex works however.  Something to work on...

[/ramble concluded]

(PS: THis is one of the Mot-homolog articles, it appears that they go for the conformation-change model also):


Biochemistry 2001 Oct 30;40(43):13041-50
Conformational change in the stator of the bacterial flagellar motor.

Kojima S, Blair DF.

Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.

MotA and MotB are integral membrane proteins of Escherichia coli that form the stator of the proton-fueled flagellar rotary motor. The motor contains several MotA/MotB complexes, which function independently to conduct protons across the cytoplasmic membrane and couple proton flow to rotation. MotB contains a conserved aspartic acid residue, Asp32, that is critical for rotation. We have proposed that the protons energizing the motor interact with Asp32 of MotB to induce conformational changes in the stator that drive movement of the rotor. To test for conformational changes, we examined the protease susceptibility of MotA in membrane-bound complexes with either wild-type MotB or MotB mutated at residue 32. Small, uncharged replacements of Asp32 in MotB (D32N, D32A, D32G, D32S, or D32C) caused a significant change in the conformation of MotA, as evidenced by a change in the pattern of proteolytic fragments. The conformational change does not require any flagellar proteins besides MotA and MotB, as it was still seen in a strain that expresses no other flagellar genes. It affects a cytoplasmic domain of MotA that contains residues known to interact with the rotor, consistent with a role in the generation of torque. Influences of key residues of MotA on conformation were also examined. Pro173 of MotA, known to be important for rotation, is a significant determinant of conformation: Dominant Pro173 mutations, but not recessive ones, altered the proteolysis pattern of MotA and also prevented the conformational change induced by Asp32 replacements. Arg90 and Glu98, residues of MotA that engage in electrostatic interactions with the rotor, appear not to be strong determinants of conformation of the MotA/MotB complex in membranes. We note sequence similarity between MotA and ExbB, a cytoplasmic-membrane protein that energizes outer-membrane transport in Gram-negative bacteria. ExbB and associated proteins might also employ a mechanism involving proton-driven conformational change.

Edited by niiicholas on Feb. 17 2003,17:53


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 07 2003,01:31   

This would appear to be in support of the "the proton passes through the MotAB complex, and the resulting change of shape moves the FliG & C-ring"


At first sight, these two systems have little in common with the flagellar motor other than the use of a trans-membrane electrochemical gradient as an energy source. The bacterial flagellum is a complex macromolecular assemblage forming a multipartite structure composed of a long helical propeller, a flexible hook region and a rotary motor in the bacterial cytoplasmic membrane (for reviews, see Blair, 1995; DeRosier, 1998). The torque generation depends on the operation of a number of motors composed of the two proteins MotA and MotB. These proteins are believed to form the stator of the motor, arranged around the periphery of the flagellar basal body, which constitutes the rotor of the motor, and interacting specifically with the protein FliG, one of the subunits that form this basal body (Zhou et al., 1998a). The suggested mechanism is that protons traverse the membrane through a 'pore' formed by the MotA and MotB proteins. This 'pore' involves, in particular, a conserved aspartate residue of MotB (Asp-32) (Zhou et al., 1998b). Two conserved proline residues of MotA (Pro-173 and Pro-222) (Braun et al., 1999) are also particularly important in torque generation. On the basis of these studies, a model has been proposed (Braun et al., 1999) in which the first proline senses a conformational state and gates proton uptake by the aspartate residue from the periplasm. The proton uptake causes a change that either permits (via a Brownian ratchet) or drives rotation, a step involving the second proline residue. Finally, proton release into the cytoplasm restores the motor to its initial state.

Let's see if this graphic works:


Eric Cascales Roland Lloubès James N Sturgis Molecular Microbiology Volume 42 Issue 3 Page 795  - November 2001  
The TolQ-TolR proteins energize TolA and share homologies with the flagellar motor proteins MotA-MotB


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 07 2003,01:48   

Bracht on the flagellum:

The Bacterial Flagellum: A Response to Goodenough


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 07 2003,02:27   

In the "A Different Way to Control a Bacterial Flagellum" category:


J Mol Microbiol Biotechnol 2002 May;4(3):183-6

Sensory transduction to the flagellar motor of Sinorhizobium meliloti.

Scharf B, Schmitt R.

Lehrstuhl fur Genetik, Universitat Regensburg, Germany.

Molecular mechanisms that govern chemotaxis and motility in the nitrogen-fixing soil bacterium, Sinorhizobium meliloti, are distinguished from the well-studied taxis systems of enterobacteria by new features. (i) In addition to six transmembrane chemotaxis receptors, S. meliloti has two cytoplasmic receptor proteins, McpY (methyl-accepting chemotaxis protein) and IcpA (internal chemotaxis protein). (ii) The tactic response is mediated by two response regulators, CheY1 and CheY2, but no phosphatase, CheZ. Phosphorylated CheY2 (CheY2-P) is the main regulator of motor function, whereas CheY1 assumes the role of a 'sink' for phosphate that is shuttled from CheY2-P back to CheA. This phospho-transfer from surplus CheY2-P to CheA to CheY1 replaces CheZ phosphatase. (iii) S. meliloti flagella have a complex structure with three helical ribbons that render the filaments rigid and unable to undergo polymorphic transitions from right- to left-handedness. Flagella rotate only clockwise and their motors can increase and decrease rotary speed. Hence, directional changes of a swimming cell occur during slow-down, when several flagella rotate at different speed. Two novel motility proteins, the periplasmic MotC and the cytoplasmic MotD, are essential for motility and rotary speed variation. A model consistent with these data postulates a MotC-mediated gating of the energizing MotA-MotB proton channels leading to variations in flagellar rotary speed.

Random points:

1) Yet another non-bidirectional flagellum

2) This flagellum has required parts that other flagella don't require (MotC and MotD)

3) Other flagella have required parts (e.g. CheZ) that this flagellum doesn't require

4) I always thought it made more sense to regulate the motor rather than the C-ring (or at least it was easier to imagine); it appears that Sinorhizobium meliloti agrees.

5) Does "rigid flagella" indicate that these guys get away without even hook proteins (the more-flexible proteins at the base of the external rod structure)?

6) Chemotaxis systems in general are a huge mess in terms of IC-interpretation. In some cases similar systems are coupled to wildly different motility systems (and probably even to nonmotility systems; cells have to react in multiple ways including motion), and some motile cells appear to get by without the chemotaxis system at all; see:


Microbiology 1999 Feb;145 ( Pt 2):279-81
A twisted tale: the origin and evolution of motility and chemotaxis in prokaryotes.

Faguy DM, Jarrell KF.


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 08 2003,01:11   

Link to extended discussion on the relative basal-ness of MotA vs. ExbB:;f=13;t=000576;p=3


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 08 2003,02:39   

Fun article, a latter day version of Purcell's "Life at Low Reynolds Number":

The efficiency of propulsion by a rotating flagellum


Proc. Natl. Acad. Sci. USA
Vol. 94, pp. 11307-11311, October 1997
The efficiency of propulsion by a rotating flagellum
(bacteria / motility / hydrodynamics / low Reynolds number)

Edward M. Purcell*

Department of Physics, Harvard University, Cambridge, MA 02138

Communicated by Howard C. Berg, Harvard University, Cambridge, MA, July 29, 1997


[At very low Reynolds number, the regime in which fluid dynamics is governed by Stokes equations, a helix that translates along its axis under an external force but without an external torque will necessarily rotate. By the linearity of the Stokes equations, the same helix that is caused to rotate due to an external torque will necessarily translate. This is the physics that underlies the mechanism of flagellar propulsion employed by many microorganisms. Here, I examine the linear relationships between forces and torques and translational and angular velocities of helical objects to understand the nature of flagellar propulsion.]

Note: the mathematical tractability of calculating diffusion and velocity for bacteria & their flagella should not be neglected.  E.g. it seems that the propulsion or dispersal potential of various "crude" flagella could be calculated.


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 17 2003,17:16   

More from Dembski on the flagellum:

ISCID thread

Dembski's latest article:
Still Spinning Just Fine: A Response to Ken Miller

My reply:

There are severe problems with basically every paragraph of Bill Dembski's latest, I will focus on just one:

Dembski writes in Still Spinning Just Fine that:


The Argument from Personal Incredulity:

Miller claims that the problem with anti-evolutionists like Michael Behe and me is a failure of imagination -- that we personally cannot "imagine how evolutionary mechanisms might have produced a certain species, organ, or structure." He then emphasizes that such claims are "personal," merely pointing up the limitations of those who make them. Let's get real. The problem is not that we in the intelligent design community, whom Miller incorrectly calls "anti-evolutionists," just can't imagine how those systems arose. The problem is that Ken Miller and the entire biological community haven't figured out how those systems arose. It's not a question of personal incredulity but of global disciplinary failure (the discipline here being biology) and gross theoretical inadequacy (the theory here being Darwin's).

However, with confronted with rather a lot of literature on the origin and evolution of the immune system (one of Behe's originally identified IC systems from Darwin's Black Box, plus lots of evidence of precursors in organisms without the full system, not a single IDist was able to defend the previous statements of Behe and Dembski along the lines of "the entire biological community ha[s]n't figured out how those systems arose."  A few of the more sophisticated ID-friendlies even appeared to agree that the gradual evolution of the "IC" immune system was a perfectly reasonable idea supported by a fair number of observations and peer-reviewed articles.

This was all done right here on ISCID not few months ago:

Organisms using GAs vs. Organisms being built by GAs

And yes, this will keep getting brought up as long as Dembski keeps repeating the same false line that biologists are clueless about how complex multipart systems can originate.

As for what things like the Type III secretion system do and do not prove (as well as for citations of important bits of evidence that Dembski failed to deal with, things like the Exb homologs of the flagellum motor proteins, and the archaeal flagellum--Type IV secretion system homologies), there's not much point in repeating them yet again, so I've been accumulating a list of the relevant links here: resource thread on the prokaryote flagella (there's more than one kind of flagellum, durnit!!! )


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 17 2003,18:07   

I got some replies to this quote I posted in response to Nelson Alonso:


So lets review. A de-novo design hypothesis entails:

1. No evolutionary history

2. IC tied in with functional constraint (selection weeding out mutants because of ICness .
Hmm, neither seems quite completely so true for the ATPase, because of the PPase.  A simpler, partially sequence-similar system can perform the task.  So even for a system older than the flagellum scientists are beginning to get hints indicating that ICness tain't all it's cracked up to be.


In the near future I want to bring Dembski into the mix. However, unless any relevant criticism of a specific system is brought up, I'm simply going to list them for now. And we can bring up another thread to discuss each system's history. For now, I'm just concerned with listing them.
Well for starters, for the flagellum your reliance on Mike Gene has left you a bit out of date:


Biochemistry 2001 Oct 30;40(43):13041-50
Conformational change in the stator of the bacterial flagellar motor.

Kojima S, Blair DF.

Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.

MotA and MotB are integral membrane proteins of Escherichia coli that form the stator of the proton-fueled flagellar rotary motor. The motor contains several MotA/MotB complexes, which function independently to conduct protons across the cytoplasmic membrane and couple proton flow to rotation. MotB contains a conserved aspartic acid residue, Asp32, that is critical for rotation. We have proposed that the protons energizing the motor interact with Asp32 of MotB to induce conformational changes in the stator that drive movement of the rotor. To test for conformational changes, we examined the protease susceptibility of MotA in membrane-bound complexes with either wild-type MotB or MotB mutated at residue 32. Small, uncharged replacements of Asp32 in MotB (D32N, D32A, D32G, D32S, or D32C) caused a significant change in the conformation of MotA, as evidenced by a change in the pattern of proteolytic fragments. The conformational change does not require any flagellar proteins besides MotA and MotB, as it was still seen in a strain that expresses no other flagellar genes. It affects a cytoplasmic domain of MotA that contains residues known to interact with the rotor, consistent with a role in the generation of torque. Influences of key residues of MotA on conformation were also examined. Pro173 of MotA, known to be important for rotation, is a significant determinant of conformation: Dominant Pro173 mutations, but not recessive ones, altered the proteolysis pattern of MotA and also prevented the conformational change induced by Asp32 replacements. Arg90 and Glu98, residues of MotA that engage in electrostatic interactions with the rotor, appear not to be strong determinants of conformation of the MotA/MotB complex in membranes. We note sequence similarity between MotA and ExbB, a cytoplasmic-membrane protein that energizes outer-membrane transport in Gram-negative bacteria. ExbB and associated proteins might also employ a mechanism involving proton-driven conformational change.


The occurrence of significant conformational change in the stator has implications not only for the present-day mechanism but also for the evolution of the flagellar motor. A membrane complex that undergoes proton-driven conformational changes could perform useful work in contexts other than (and simpler than) the flagellar motor, and ancestral forms of the MotA/MotB complex might have arisen independently of any part of the rotor. We queried the sequence database using the sequence of the best-conserved part of MotA (the segment containing membrane segments 3 and 4) from Aquifex aeolicus, a species whose lineage is deeply branched from other bacteria. In addition to the expected MotA homologues, the search returned a protein sequence from the archaeal species Methanobacterium thermoautotrophicum (protein MTH1022) that shows significant sequence similarity not only to MotA but also to the protein ExbB (Figure 9). ExbB is a cytoplasmic-membrane protein that functions in conjunction with ExbD, TonB, and outer-membrane receptors to drive active transport of certain essential nutrients across the outer membrane of Gram-negative bacteria. The energy for this transport comes from the proton gradient across the inner membrane. Thus, MotA and ExbB are both components of systems that tap the proton gradient to do work some distance away (at either the rotor-stator interface or the outer membrane; Figure 9).

Other features also point to a connection between the Mot and Exb systems. MotA functions in a complex with MotB, which as noted contains the critical residue Asp32 near the cytoplasmic end of its single membrane segment. ExbB functions in a complex with ExbD, which likewise has a single membrane segment with a critical Asp residue near its cytoplasmic end (Asp25 in ExbD of E. coli; ref 59). Although ExbB has only three membrane segments in contrast to the four in MotA, the membrane segments that show sequence similarity have the same topology. The protein TonB is also present in the complex with ExbB and ExbD (59, 60) and would provide an additional membrane segment to round out the topological correspondence (Figure 9). ExbB contains a well-conserved Pro residue (Pro141 in E. coli ExbB) that is the counterpart of Pro173 of MotA. Although MotB and ExbD do not share close sequence similarity apart from the critical Asp residue, in certain positions in the membrane segment the residues most common in MotB proteins are also common in ExbD proteins. Finally, like the MotA/MotB complex the ExbB/ExbD complex contains multiple copies of each protein (61). Together, these facts make a reasonable case for an evolutionary connection between the Mot proteins of the flagellar motor and the Exb proteins of outer-membrane transport (and by extension the TolQ/TolR proteins, which are related to ExbB/ExbD but whose functions are less understood).

The number of parts in a flagellum that don't have homologs with different, non-flagellar functions is getting to be rather low; mostly they are filament and shaft proteins, which all may be homologous with each other, and of course nonmotile filaments are known to have a wide degree of uses in bacteria...

So even for systems that are remote from us by 3 billion years there has been some recent progress.  


...from this ARN thread:;p=3

...and then Nelson replied and I replied:

Originally posted by Nelson Alonso:
I also want to read your reference concerning bacterial flagellar motor, but to be honest, I already see it as irrelevant, since sequence similarity doesn't tell me much about how to make a bacterial flagellum via natural selection and random mutation.
Hmm, Mike Gene didn't think that such a thing was irrelevant:

MotA/MotB, on the other hand, could plausibly exist as some ion channel prior to the existence of the flagella, but there is no evidence of this.
And yet soon after he wrote this, exactly such homologous-but-non-flagellar ion channel was discovered.  Looks to me like this family of enzymes couples proton flow to all kinds of mechanical processes, only one of which is rotating the base of the flagellum.

And he also wrote:


[snipped image for formatting sake]

Figure 1. The EFM Hypothesis. It begins with multi-component export machinery and invokes an initial cooption even to explain the origin of the filament. But because the "filament" of the flagellum is also a multi-component system, simultaneous, not gradual cooption is being invoked. Its non-flagellar function is not provided. The second cooption event, where an ion channel is added to create the flagellum, invokes the same thing.
But a plausibly pre-existing function for stage 2 (now) *has* been provided.  And, strangely enough (except from the perspective of the cooption hypothesis), the first reasonably strong homology evidence for a pre-existing functional subcomponent of the flagellum *just happens* to be the last two parts added in the cooption scenario, which just happen to already function together just like they do in the flagellum.  

(I don't see any good reason for MG's breaking what is otherwise convention and splitting off FlG's C-terminal end as a "separate" part, seems to me this is a special maneuvure not utilized elsewhere)


The bacterial motor allows movement at such a speed that, if the bacteria were resized to the weight of cars, they would supposedly break the sound barrier.
If you follow this analogy, the car when "sitting still" would be "jiggling" many times its body length every second due to brownian motion.  Your driveway and house would be ruined.  Intuition is a poor guide to life at the very small scale.


The Exb complex are homologs but quite distant from the Mot complex, and even the function is completely different.
All depends on what you mean by "function".  Kojima and Blair didn't think so.  As for distance, the proposed cooption event did occur at something like the common ancestor of eubacterial, so there has been a bit o'time for divergence.

....And when Nelson still wasn't impressed, I wrote:

Um, Nelson, you didn't even read the quote I provided:


We queried the sequence database using the sequence of the best-conserved part of MotA (the segment containing membrane segments 3 and 4) from Aquifex aeolicus, a species whose lineage is deeply branched from other bacteria. In addition to the expected MotA homologues, the search returned a protein sequence from the archaeal species Methanobacterium thermoautotrophicum (protein MTH1022) that shows significant sequence similarity not only to MotA but also to the protein ExbB (Figure 9). ExbB is a cytoplasmic-membrane protein that functions in conjunction with ExbD, TonB, and outer-membrane receptors to drive active transport of certain essential nutrients across the outer membrane of Gram-negative bacteria. The energy for this transport comes from the proton gradient across the inner membrane.
See that?  A homolog in archaebacteria.  As far as our current understanding of microbial phylogeny allows us to say anything about what is basal to what, it appears that the MotA homolog is more basally distributed than the eubacterial flagellum.  So if you're going to use distribution as a guide to what came first, you lose on this one.

Of course, given the uncertainty surrounding phylogenetic events 3.5 billion years ago, not to mention lateral transfer events etc., the most reasonable thing to do would be to say that we have no particularly good information about what came before what.  But then there goes any confidence in the assertion that bacteria have always had flagella or have no precursor homologous proteins, which has been a big chunk
of your argument.

Regarding the probability of this ion channel hooking up to the base of a primitive Type III pili, the exact mechanism of coupling proton flow to motion is still up in the air.  However, you wouldn't have to get a fully functioning flagellum out of it, even undirected wiggling would enhance dispersal.  This provides the starting point for natural selection to refine the procedure.

As you and Mike Gene point out, such a getting-the-process-started mutation is an unlikely "completely chance event" -- but just like any mutation, this is not a one-try event!!!  Give a few gaztrillion bacteria a few million years!  And we are clearly no longer dealing with the fortuitous de novo synthesis of a whole bunch of proteins, as Dembski suggests, or even the fortuitous cooption of dozens of individual proteins all at once, as Mike Gene sometimes mischaracterizes cooption.  We are just hypothesizing a mutation crudely coupling two pre-existing systems.

As for similarity in function, Kojima and Blair note that this basic ion-channel system has been successfully coupled to diverse systems:

Thus, MotA and ExbB are both components of systems that tap the proton gradient to do work some distance away (at either the rotor-stator interface or the outer membrane; Figure 9).
The point with the brownian motion analogy is that "faster than the speed of sound" is not quite so impressive on the molecular scale.  Considering that some bacteria get by with relatively slow motility systems, and many get by with none at all, argues that we should keep the niftiness of the flagellum in perspective.  Another random fact: the energetic efficiency of the flagellum is at best a few percent according to Berg's Random Walks in Biology.

And then in reply to a few objections from Mike Gene:

First off,

An awful lot of entries in the NCBI protein database listing MotA, ExbB, and TolQ as being a "family", in opposition to what Mike Gene has been suggesting

Originally posted by Mike Gene:
Nic: Hey, I'm just following the peer-reviewed lit., man. Take it up in the pages of Biochemistry if you like...

The authors never claim MTH1022 is a homolog of motA. And even if they did, the claim would be unsupported.  
People can read the quote I posted and decide for themselves exactly what the authors meant.  Mentioning significant sequence similarity in the middle of a discussion of homologs seems like a strong indication to me that they meant homolog or at least "likely homolog".  And see below for what some of those proteins are labeled as in the NCBI database.


Actually, running a PSI-BLAST of ExbB gets me four hits on archaeabacteria, but whatever.

With e values of 0.005 and higher.  That's not very impressive.  Furthermore, even if there is a non-convergent and real relationship here, note that it is not widely distributed and would thus seem to have evolved long after archaea appeared.  

A much stronger point is that the ExbB homologs are very widely distributed in eubacteria, in very basal lineages.

Think so?  What groups did you have in mind?[/qb]
Hmm, well a standard protein BLAST  on E coli ExbB gives me this taxonomy report:

An E. coli "biopolymer transport exbB protein"

Here is the link

Here are some of the results *outside* the proteobacteria:

Code Sample
 Chlamydophila pneumoniae CWL029 [chlamydias] taxid 115713
gi|15618694|ref|NP_224980.1| Macromolecule transporter [Ch...      61  1e-08

 Cytophaga hutchinsonii [CFB group bacteria] taxid 985
gi|23136461|gb|ZP_00118181.1| hypothetical protein [Cytoph...      60  1e-08
gi|23136843|gb|ZP_00118557.1| hypothetical protein [Cytoph...      36  0.35

 Chlamydia trachomatis [chlamydias] taxid 813
gi|15605326|ref|NP_220112.1| polysaccharide transporter [C...      59  4e-08

 Chlamydia muridarum (agent of mouse pneumonitis) [chlamydias] taxid 83560
gi|15835499|ref|NP_297258.1| MotA/TolQ/ExbB proton channel...      58  8e-08

 Aquifex aeolicus [aquificales] taxid 63363
gi|15606982|ref|NP_214364.1| TolQ homolog [Aquifex aeolicu...      55  5e-07
gi|15606823|ref|NP_214203.1| biopolymer transport exbB [Aq...      42  0.005


 Deinococcus radiodurans [eubacteria] taxid 1299
gi|15805483|ref|NP_294179.1| biopolymer transport protein,...      47  1e-04

 Methanothermobacter thermautotrophicus str. Delta H [euryarchaeotes] taxid 187420
gi|15679040|ref|NP_276157.1| biopolymer transport protein ...      43  0.002

 Synechocystis sp. PCC 6803 [cyanobacteria] taxid 1148
gi|16329196|ref|NP_439924.1| biopolymer transport ExbB pro...      41  0.013
gi|16329550|ref|NP_440278.1| biopolymer transport ExbB pro...      40  0.018

Note below that *even* some proteobacteria ExbB proteins have "unimpressive" similarity scores and yet are still called ExbB proteins (as are some **archaeabacteria** ExbB-family proteins):

Code Sample
Photobacterium damselae subsp. piscicida [g-proteobacteria] taxid 38294
gi|19577341|emb|CAD27898.1| ExbB protein [Photobacterium d...      33  1.9

 Plesiomonas shigelloides [enterobacteria] taxid 703
gi|13774064|gb|AAG23397.1| ExbB [Plesiomonas shigelloides]         33  2.0

 Sulfolobus solfataricus [crenarchaeotes] taxid 2287
gi|15899059|ref|NP_343664.1| Amino acid transporter, putat...      33  2.6


 Methanosarcina acetivorans C2A [euryarchaeotes] taxid 188937
gi|20089242|ref|NP_615317.1| MotA/TolQ/ExbB proton channel...      33  3.4
gi|20093212|ref|NP_619287.1| MotA/TolQ/ExbB proton channel...      33  3.8
gi|20093420|ref|NP_619495.1| MotA/TolQ/ExbB proton channel...      32  6.7
MotA and ExbB appear to have equally wide distributions

The distribution taxonomy report for ExbB is, in fact, rather like the taxonomy report for standard protein blast of E. coli's MotA protein: lots and lots of enterobacteria and proteobacteria, and a few hits out in spirochetes and other various deeply divergent bacteria.

Here is said taxonomy report

Are we to conclude that MotA is just as likely to be of late origin and derived as ExbB?

...methinks the database may be a wee bit biased towards certain intensively-studied gram-negative bacteria groups and that therefore seeing many hits in those groups and few outside means very little in terms of relative significance.  As I showed, you have to put MotA and ExbB in the same distribution bucket regardless.

Regarding low e-values:

Based on your blanket skepticism of marginal e-values, you may want to argue that some MotA proteins are of independent origins and convergent on standard MotA's.  Many of these scores are non too impressive, yet some are MotAs (or PomA, a related motor) despite this:

Code Sample
 Treponema denticola [spirochetes] taxid 158
gi|4426945|gb|AAD20619.1| flagellar motor protein MotA [Tr...      53  3e-06

 Pseudomonas putida [g-proteobacteria] taxid 303
gi|2853602|gb|AAC08066.1| MotA [Pseudomonas putida]                53  5e-06

 Leptospira interrogans serovar lai str. 56601 [spirochetes] taxid 189518
gi|24213362|ref|NP_710843.1| Chemotaxis motA protein [Lept...      52  6e-06
gi|24216276|ref|NP_713757.1| motility protein A [Leptospir...      39  0.056

 Bacillus anthracis str. A2012 [eubacteria] taxid 191218
gi|21402555|ref|NP_658540.1| MotA_ExbB, MotA/TolQ/ExbB pro...      52  8e-06
gi|21399546|ref|NP_655531.1| MotA_ExbB, MotA/TolQ/ExbB pro...      51  1e-05

 Shewanella oneidensis MR-1 [g-proteobacteria] taxid 211586
gi|24375769|ref|NP_719812.1| chemotaxis motA protein [Shew...      51  1e-05
gi|24373102|ref|NP_717145.1| chemotaxis motA protein [Shew...      38  0.13

 Thermotoga maritima [thermotogales] taxid 2336
gi|15643440|ref|NP_228484.1| motility protein A [Thermotog...      50  3e-05

 Campylobacter jejuni [e-proteobacteria] taxid 197
gi|15791705|ref|NP_281528.1| putative flagellar motor prot...      48  9e-05

 Rhodopseudomonas palustris [a-proteobacteria] taxid 1076
gi|22963976|gb|ZP_00011582.1| hypothetical protein [Rhodop...      42  0.006

 Magnetococcus sp. MC-1 [proteobacteria] taxid 156889
gi|22999422|gb|ZP_00043404.1| hypothetical protein [Magnet...      41  0.011
gi|23000123|gb|ZP_00044067.1| hypothetical protein [Magnet...      33  3.5

 Vibrio alginolyticus [g-proteobacteria] taxid 663
gi|3024412|sp|O06873|POMA_VIBAL Chemotaxis pomA protein >g...      40  0.038

 Bacillus halodurans [eubacteria] taxid 86665
gi|15615802|ref|NP_244106.1| flagellar motor apparatus [Ba...      39  0.058

 Vibrio vulnificus CMCP6 [g-proteobacteria] taxid 216895
gi|27363787|ref|NP_759315.1| Flagellar motor component Mot...      37  0.18

 Clostridium thermocellum ATCC 27405 [eubacteria] taxid 203119
gi|23021959|gb|ZP_00061601.1| hypothetical protein [Clostr...      35  0.87

 Vibrio cholerae [g-proteobacteria] taxid 666
gi|15640908|ref|NP_230539.1| chemotaxis protein PomA [Vibr...      32  5.6
Regarding the e-values of archaeal ExbB homologs, PSI-BLAST on E. coli ExbB gives an archaeabacterial homolog with e-value of 2e-17, which ought to be good enough for Mike Gene:

PSI-BLAST search

 Methanothermobacter thermautotrophicus str. Delta H [euryarchaeotes] taxid 187420
gi|15679040|ref|NP_276157.1| biopolymer transport protein ...      90  2e-17
gi|15678698|ref|NP_275813.1| unknown [Methanothermobacter ...      43  0.003
gi|15678311|ref|NP_275426.1| protein kinase [Methanothermo...      33  3.4
My point

These kinds of things ought to at least be mentioned and discussed before reckless statements are made about absolutely no evidence for precursors to flagellar proteins, that's my only point.  For some reason you guys prefer to sweep it under the rug by unsupported arguments about ExbB's narrow distribution.  Just acknowledge that this little bit of the biological world is a bit disharmonious with the flagellum-was-specially-created thesis.  All I've been saying, and now documenting, is that ExbB homologs are at least as widely distributed as MotA, and possibly more widely distributed.

Edited by niiicholas on Feb. 17 2003,18:09


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 17 2003,20:12   

Old posts on the topic:

Mot homologies in context of Musgrave's Flagellum FAQ

The bacterial flagellum evolved (scroll down to get the best post)

Beating a dead horse, or, flagellating the flagellum

Evolving the Bacterial Flagellum by Mike Gene (and unfortunately, MG's essay still hasn't been finished as far as I can tell)

Edited by niiicholas on Feb. 17 2003,20:17


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 17 2003,22:06   

Link to:

ARN discussion


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 18 2003,18:45   

Heh.  Check this out.  I never spent much time on the nonstructural components of the bacterial flagellum, since pretty much everyone focuses on the structural parts, but Dembski in his recent essay apparently was getting nervous that too many structural parts had been given alternative functions, and so he made reference to all of the nonstructural genes involved.

So I did a search on chemotaxis genes.  Look what I found:


Mol Biol Evol 2000 Dec;17(12):1956-70
Evolution of two-component signal transduction.

free full article online

Koretke KK, Lupas AN, Warren PV, Rosenberg M, Brown JR.

SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania 19426-0989, USA.

Two-component signal transduction (TCST) systems are the principal means for coordinating responses to environmental changes in bacteria as well as some plants, fungi, protozoa, and archaea. These systems typically consist of a receptor histidine kinase, which reacts to an extracellular signal by phosphorylating a cytoplasmic response regulator, causing a change in cellular behavior. Although several model systems, including sporulation and chemotaxis, have been extensively studied, the evolutionary relationships between specific TCST systems are not well understood, and the ancestry of the signal transduction components is unclear. Phylogenetic trees of TCST components from 14 complete and 6 partial genomes, containing 183 histidine kinases and 220 response regulators, were constructed using distance methods. The trees showed extensive congruence in the positions of 11 recognizable phylogenetic clusters. Eukaryotic sequences were found almost exclusively in one cluster, which also showed the greatest extent of domain variability in its component proteins, and archaeal sequences mainly formed species-specific clusters. Three clusters in different parts of the kinase tree contained proteins with serine-phosphorylating activity. All kinases were found to be monophyletic with respect to other members of their superfamily, such as type II topoisomerases and Hsp90. Structural analysis further revealed significant similarity to the ATP-binding domain of eukaryotic protein kinases. TCST systems are of bacterial origin and radiated into archaea and eukaryotes by lateral gene transfer. Their components show extensive coevolution, suggesting that recombination has not been a major factor in their differentiation. Although histidine kinase activity is prevalent, serine kinases have evolved multiple times independently within this family, accompanied by a loss of the cognate response regulator(s). The structural and functional similarity between TCST kinases and eukaryotic protein kinases raises the possibility of a distant evolutionary relationship.


Two-component signal transduction (TCST) pathways form the central signaling machinery in bacteria (for reviews, see Stock, Ninfa, and Stock 1989 ; Parkinson and Kofoid 1992 ; Hoch and Silhavy 1995 ). In response to a stimulus, typically extracellular, the kinase component autophosphorylates at an internal histidine (the H-box). The high-energy phosphate group is then transferred to an aspartyl residue on the response regulator component (hence, "two-component" signal transduction), which modifies cellular behavior via an effector domain (fig. 1 ). Although most systems use a linear phosphorelay from one kinase to one response regulator, some use more complicated paths, involving a branching of the signal (chemotaxis) or multiple phosphorylated components (sporulation, adaptation to anaerobic conditions).

Code Sample

[b]Fig. 1.[/b]—Schematic diagram illustrating phosphorelay in two-component signal transduction systems. The signal (usually coming from the extracellular environment) is transduced to the "linker" region, which is located adjacent to the last transmembrane helix of the membrane-bound protein. The linker interacts with the kinase domain to induce autophosphorylation at a histidine (shown in red) located in the His-box domain or—in [b]CheA[/b]—in the Hpt domain. The phosphate is then transferred to an aspartate residue (shown in red) in a response regulator domain. The phosphorylated response regulator elicits the appropriate response within the cell (typically via the DNA-binding activity of an effector domain). In some systems, an Hpt domain serves as a regulatory phosphate sink for the phosphorylated response regulator

In bacteria, TCST systems mediate adaptive responses to a broad range of environmental stimuli. These include citrate uptake and catabolism (Cit), aerobic respiration (Arc), osmoregulation (EnvZ/OmpR), stress-induced sporulation (Kin/Spo), N-acetylmuramoyl-l-alanine amidase biosynthesis (Lyt), nitrate and nitrite metabolism (Nar), nitrogen regulation (Ntr), phosphate regulation (Pho), host recognition for pathogen invasion (Vir), and chemotaxis (Che) (Stock, Ninfa, and Stock 1989 ; Parkinson and Kofoid 1992 ; Hoch and Silhavy 1995 ). TCST systems also exist in certain nonanimal eukaryotes and in some Archaea (Alex and Simon 1994 ; Loomis, Shaulsky, and Wang 1997). In plants, they mediate photosensitivity (Schneider-Poetsch et al. 1991 ; Yeh and Lagarias 1998 ) and ethylene response (Chang et al. 1993 ); in fungi, they mediate osmoregulation (Maeda, Wurgler-Murphy, and Saito 1994 ; Krems, Charizanis, and Entian 1996 ; Posas et al. 1996 ) and hyphal development (Alex, Borkovich, and Simon 1996 ; Alex et al. 1998 ); and in the slime mold, they mediate Dictyostelium discoideum osmoregulation (Schuster et al. 1996 ) and fruiting body formation (Singleton et al. 1998 ). A thorough cataloguing of protein kinases found in the genome of the nematode Caenorhabditis elegans failed to find any true orthologs to prokaryotic histidine kinases, which suggests that TCST systems do not occur in metazoans (Plowman et al. 1999 ).


An exception to the phosphorelay described here is found in the chemotaxis kinase CheA, where the H-box has lost the catalytic histidine and is used exclusively for dimerization, while an Hpt domain that may have originally served a regulatory function is now used for phosphorelay to CheY and CheB (Bilwes et al. 1999 ; Dutta, Qin, and Inouye 1999 ). Further variability in His-acceptor domains is seen in the Spo0B protein, whose H-box domain forms a dimeric four-helix bundle similar to canonical H-boxes but of opposite handedness (Varughese 1998 ).

In addition to the three phosphorelay domains described above, a fourth domain conserved broadly in TCST systems has recently been recognized (Park and Inouye 1997 ; Aravind and Ponting 1999 ). Termed the "linker" region (or HAMP domain), it is typically found at the C-terminal end of the last transmembrane segment in many histidine kinases, chemoreceptors, bacterial nucleotidyl cyclases, and phosphatases, and mutations show that it plays a critical role in signal transduction. Some proteins contain multiple copies in tandem, suggesting that it represents an autonomously folding unit. Its ability to regulate kinase activity in trans (e.g., between chemoreceptors and CheA) and the variable nature of the segments connecting it to the H-box suggest that it acts through direct interaction with the kinase domain rather than through propagation of conformational change along the polypeptide chain. Thus, four protein domains appear to be typically involved in the signal transduction pathway from the extracellular sensor domain to the cytoplasmic effector (fig. 1 ).

TCST systems represent one of the most studied and best understood areas of bacterial physiology. Recently, they have also emerged as attractive targets for anti-microbial drug development (Barrett et al. 1998 ; Lange et al. 1999 ; Throup et al. 2000). Here we report the results of a detailed phylogenetic and structural study of genomic TCST sequences, undertaken to explore the origin and evolution of TCST systems.


Several interesting observations follow from the phylogenetic clusters presented here: No cluster contained proteins from both Archaea and eukaryotes, although a specific evolutionary relationship has long been postulated between these two groups (reviewed in Brown and Doolittle 1997 ). Bacterial phylogeny similarly did not correlate well with the observed clustering. Despite the considerable sizes of some clusters, none contained representatives from each bacterial species, and no bacterium had a representative in all of the clusters. Among bacteria, no cluster predominated across all species: Pho contained nearly a third of all TCST proteins detected in E. coli, B. subtilis, and Synechocystis and two thirds of those in M. tuberculosis, but none from spirochetes. In the latter, Che which is missing from A. aoelicus and M. jannaschii, was predominant (even though both organisms encode flagellar proteins and are motile). [a little garbled, I think this means these particular guys don't have Che proteins, e.g.:

"Among the Archaea, Methanobacterium thermoautotrophicum and Archaeoglobus fulgidus contained the largest numbers of histidine kinases (16 and 14, respectively) and response regulators (10 and 11, respectively), although they still contained fewer than free-living bacteria. Pyrococcus horikoshii had only a single histidine kinase and two response regulators (corresponding to the chemotaxis proteins CheA, CheY, and CheB), while Methanococcus jannaschii, Aeropyrum pernix, and Thermoplasma acidophilum had none. "]

Origin of the Histidine Kinase Fold
Response regulators are not recognizably related to other known protein families beyond a general structural similarity to P-loop NTPases (such as Ras) (Lukat et al. 1991 ; Stock et al. 1993 ), which has hitherto not been considered sufficient to infer homology. Histidine kinases, however, are clearly related to Hsp90, MutL, and type II topoisomerases in the ATP-binding domain (Tanaka et al. 1998 ; Bilwes et al. 1999 ; Dutta, Qin, and Inouye 1999 ). The conserved structural core consists of an antiparallel, four-stranded ß-sheet flanked on one side by three -helices, which surround the ATP-binding site. In addition, an ß element, which is in an equivalent structural position, is circularly permuted in the sequence of histidine kinases relative to other proteins with this fold. The structural similarity is mirrored in a set of conserved sequence motifs, primarily associated with nucleotide binding, which strongly imply descent from a common ancestor (fig. 4A ). Phylogenetic analysis of the sequence data by distance methods indicates that all kinases in this superfamily arose from a single ancestral protokinase (fig. 4B ). Because of the low branch point of PDKs, it is unclear whether this ancestor had Ser- or His-phosphorylating activity.

Histidine Kinases and Response Regulators Have Coevolved

In this study, we analyzed the phylogenetic relationships between the TCST systems from 14 complete and 6 partial genomes. Their components represent highly evolved multigene families, and the pattern and process of proliferation of such interacting yet structurally unrelated proteins is an important problem in evolutionary biology. A priori, two competing models for the evolution of novel TCST systems appear plausible: the recruitment model and the coevolution model. The recruitment model suggests that novel TCST systems evolve through gene duplication of one component, which then co-opts components from heterologous systems to yield a new specificity. This model is supported by the structural similarity of response regulators, in which only a few residues are sufficient to determine specificity, and by the observed crosstalk of TCST systems within an organism. From the phylogenetic perspective, this mechanism would result in an incongruent clustering of cognate histidine kinases and response regulators. The coevolution model suggests that novel TCST systems evolve by global duplication of all their components and subsequent differentiation. This model is supported by the fact that many TCST systems are concurrent on the chromosome. Phylogenetically, this mechanism would produce congruent gene trees for histidine kinases and response regulators.

Our results support the coevolution model. Despite the large number of proteins considered, which limited the resolution of the analysis by lowering the ratio of aligned residues to OTUs, the trees obtained for the histidine kinase and response regulator domains showed congruent clustering (fig. 2 ). Although the precise evolutionary relationships between clusters were not supported by strong bootstrap values, the overall topology of the NJ histidine kinase tree was verified by heuristic search results for the minimal-length MP tree. No such support was obtained for the response regulator tree, which had a lower resolution, but its validity was verified by the occurrence of two superclusters (Arf/Cit/CheY/Lyt and Nar/Mth) that were also found in the histidine kinase tree. The clusters themselves were statistically much more robust, with over half receiving bootstrap support of >50% in the distance-based analysis. As required by the coevolution model, pairs of histidine kinases and response regulators that are known to interact were overwhelmingly found in cognate clusters, as were 89% of histidine kinase and response regulator pairs that are linked on the chromosome (fig. 3 ). Coevolution has previously been proposed for eukaryotic TCST proteins, as well as for two hybrid kinases of E. coli (BarA and RcsC) (Pao and Saier 1997 ). Hybrid kinases, however, also provide evidence for a recruitment mechanism at work. For example, four of the five hybrid kinases of E. coli (ArcB, TorS, RcsC, and EvgA) are known to signal through response regulators found in noncognate clusters, and the fifth one, BarA, is thought to do so as well (via OmpR, found in the Pho cluster) (Hoch and Silhavy 1995 ). Recruitment is also observed in the chemotaxis and sporulation systems. Nevertheless, coevolution appears to be the strongly predominant mechanism by which novel TCST systems arise. Similar patterns of molecular coevolution have been observed in other interacting proteins, such as neuropeptides and their receptors (Darlinson and Richter 1999 ) and chaperonin subunits (Archibald, Logsdon, and Doolittle 1999 ).

Coevolution is not limited to TCST proteins, but also extends to the domains forming them. Both domain shuffling and domain swapping are comparatively rare events, and, with few exceptions, response regulators having homologous carboxyl-terminal domains were found within one cluster. These results agree well with a previous study performed on 49 bacterial response regulators by Pao and Saier (1995) , who found that classes of response regulators, defined by homology of their carboxyl-termini, generally formed distinct phylogenetic clusters. Pao and Saier's (1995) classes 1–5 correspond—in order—to our phylogenetic clusters Ntr, Pho, Nar, CheB, and Hybrid; classes 6 and 7 were phylogenetically heterogeneous in both studies.

Histidine Kinases and Eukaryotic Protein Kinases—Homology or Analogy?
A distance-based phylogenetic analysis of proteins containing a histidine kinase–like ATP-binding domain, which include type II topoisomerases, Hsp90, and MutL, indicated that all kinase domains with this fold are monophyletic and confirmed that the PDKs form an outgroup to the histidine kinase clade (fig. 4B ). Searches for more distantly related proteins surprisingly suggested a similarity to the small lobe of protein kinases, which is also involved in ATP binding. The structurally similar region covers virtually the entire conserved core of both folds but is circularly permuted in the protein kinase small lobe (fig. 5A ). The amino- and carboxyl-termini of the histidine kinase fold are in close proximity, however (a prerequisite of circular permutation), and circular permutation events have been documented in the evolution of many protein folds (see the SCOP database at; Lo Conte et al. 2000 ), including the histidine kinase fold (Bilwes et al. 1999 ). Although the protein kinase small lobe is part of the so-called ATP-grasp fold (jointly with the peptide-binding large lobe), a recent structural analysis by Grishin (1999) has concluded that only the large lobe is homologous among the members of this fold, with the small lobe having been recruited among structurally similar but unrelated proteins. Our analysis supports an independent evolutionary origin of the small and large lobes of eukaryotic protein kinases.

Despite the fact that the structural similarity between histidine kinases and protein kinases is remote, the signaling pathways in which the two types of kinase operate present intriguing similarities. Both form homodimers, which phosphorylate in trans and generally contain an extracellular sensory domain, which binds signaling molecules asymmetrically at the subunit interface. They have a common mode of signal transduction, as shown by the phytochromes Phy1 and Phy2 of the moss Ceratodon purpureus, which are 90% identical in the chromophore-binding domain, yet signal through protein kinase and histidine kinase domains, respectively (fig. 5C ). Functional chimeras have also been constructed between the sensory domain of the Tar chemoreceptor and both protein and histidine kinases (Moe, Bollag, and Koshland 1989 ; Utsumi et al. 1989). Finally, as discovered recently, both kinase types use adaptors with an SH3-fold for interaction with other proteins (Bilwes et al. 1999 ). Similar parallels can be drawn between response regulators and the Ras family of G-proteins (Lukat et al. 1991 ). Not only are both encoded by large multigene families, linking different sensory inputs to specific effector outputs, but they are both activated by a high-energy phoshoanhydride bond. Their striking structural similarity, particularly in the active site, has previously been interpreted as evidence for homology rather than analogy (Artymiuk et al. 1990 ). Although each of these similarities may have arisen by convergent evolution, the combination of structural and functional parallels that can be drawn throughout signaling pathways in bacteria and eukaryotes suggest that a prototypical signal transduction pathway may already have existed in the last common ancestor and that this pathway utilized protein phosphorylation. If so, yet a third group of kinases (possibly showing similarly profound structural changes) remains to be discovered in Archaea, where bacterial- and eukaryotic-type kinases are rare and clearly acquired by horizontal transfer.
(bolds added)

My brief summary: some good hints about the ultimate origin of histidine kinases, some faint hints about the ultimate origin of response regulators, but: clear evidence that key flagellar chemotaxis proteins served a multitude of other roles prior to being flagellar.

Edited by niiicholas on Feb. 18 2003,18:50


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 19 2003,03:09   

In the "just how precise would the organization of flagellum operons really have to be to get a minimal functioning flagellum?" category:


Kalir S, McClure J, Pabbaraju K, Southward C, Ronen M, Leibler S, Surette MG, Alon U.

Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria.

Science. 2001 Jun 15;292(5524):2080-3.

The recent advances in large-scale monitoring of gene expression raise the challenge of mapping systems on the basis of kinetic expression data in living cells. To address this, we measured promoter activity in the flagellar system of Escherichia coli at high accuracy and temporal resolution by means of reporter plasmids. The genes in the pathway were ordered by analysis algorithms without dependence on mutant strains. The observed temporal program of transcription was much more detailed than was previously thought and was associated with multiple steps of flagella assembly.


The precise order of transcription of the various operons is probably not essential for assembling functional flagella. This is suggested by complementation experiments in which the motility of flagella mutants was
rescued by expression of the wild-type gene from a foreign promoter (1). The detailed transcription order could, however, function to make flagella synthesis more efficient, be-cause parts are not transcribed earlier than
needed. (p.2082)

Edited by niiicholas on Feb. 19 2003,03:10


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 20 2003,22:54   


J Bacteriol 2003 Mar;185(5):1624-33
Role of the Cytoplasmic C Terminus of the FliF Motor Protein in Flagellar Assembly and Rotation.

Grunenfelder B, Gehrig S, Jenal U.

Division of Molecular Microbiology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.

Twenty-six FliF monomers assemble into the MS ring, a central motor component of the bacterial flagellum that anchors the structure in the inner membrane. Approximately 100 amino acids at the C terminus of FliF are exposed to the cytoplasm and, through the interaction with the FliG switch protein, a component of the flagellar C ring, are essential for the assembly of the motor. In this study, we have dissected the entire cytoplasmic C terminus of the Caulobacter crescentus FliF protein by high-resolution mutational analysis and studied the mutant forms with regard to the assembly, checkpoint control, and function of the flagellum. Only nine amino acids at the very C terminus of FliF are essential for flagellar assembly. Deletion or substitution of about 10 amino acids preceding the very C terminus of FliF resulted in assembly-competent but nonfunctional flagella, making these the first fliF mutations described so far with a Fla(+) but Mot(-) phenotype. Removal of about 20 amino acids further upstream resulted in functional flagella, but cells carrying these mutations were not able to spread efficiently on semisolid agar plates. At least 61 amino acids located between the functionally relevant C terminus and the second membrane-spanning domain of FliF were not required for flagellar assembly and performance. A strict correlation was found between the ability of FliF mutant versions to assemble into a flagellum, flagellar class III gene expression, and a block in cell division. Motile suppressors could be isolated for nonmotile mutants but not for mutants lacking a flagellum. Several of these suppressor mutations were localized to the 5' region of the fliG gene. These results provide genetic support for a model in which only a short stretch of amino acids at the immediate C terminus of FliF is required for flagellar assembly through stable interaction with the FliG switch protein.


Posts: 319
Joined: May 2002

(Permalink) Posted: Feb. 21 2003,02:47   

Martino Rizzotti published a book, Early Evolution, in 2000, which presents a reasonably detailed scenario deriving the flagellum from an F1F0 ATPase.  Compared to other options it is not particularly convincing, although he does rather better at it than one might otherwise expect.

But, it is published, here are some online links:

Google search

Cavalier-Smith was fairly critical of the book in his review, but does cite the flagellum scenario in passing in one of his articles.



Posts: 319
Joined: May 2002

(Permalink) Posted: Mar. 02 2003,21:03   

On the subject of how a proto-flagellum would be positioned on the cell surface, it occurred to me awhile ago that it wouldn't matter if the cell was spherical shaped (coccus).

E.g. like this bacterium:  

Zaar A, Fuchs G, Golecki JR, Overmann J.
Arch Microbiol 2003 Mar;179(3):174-83
A new purple sulfur bacterium isolated from a littoral microbial mat, Thiorhodococcus drewsii sp. nov.

A new strain of purple sulfur bacterium was isolated from a marine microbial mat sampled in Great Sippewissett Salt Marsh at the Atlantic coast (Woods Hole, Mass., USA). Single cells of strain AZ1 were coccus-shaped, highly motile by means of a single flagellum, and did not contain gas vesicles. Intracellular membranes were of the vesicular type. However, additional concentric membrane structures were present. The photosynthetic pigments were bacteriochlorophyll a and carotenoids of the normal spirilloxanthin series, with rhodopin as the dominant carotenoid. Hydrogen sulfide (up to 11 mM), sulfur, thiosulfate, and molecular hydrogen were used as electron donors during anaerobic phototrophic growth. During growth on sulfide, elemental sulfur globules were transiently stored inside the cells. Strain AZ1 is much more versatile than most other Chromatiaceae with respect to electron donor and organic substrates. In the presence of CO(2), it is capable of assimilating C(1)-C(5) fatty acids, alcohols, and intermediates of the tricarboxylic acid cycle. Strain AZ1 could also grow photoorganotrophically with acetate as the sole photosynthetic electron donor. Chemotrophic growth in the dark under microoxic conditions was not detected. Optimum growth occurred at pH 6.5-6.7, 30-35 degrees C, >/=50 micro mol quanta m(-2) s(-1), and 2.4-2.6% NaCl. The DNA base composition was 64.5 mol% G+C. Comparative sequence analysis of the 16S rRNA gene confirmed that the isolate is a member of the family Chromatiaceae. Sequence similarity to the most closely related species, Thiorhodococcus minor DSMZ 11518(T), was 97.8%; however, the value for DNA-DNA hybridization between both strains was only 20%. Because of the low genetic similarity and since strain AZ1 physiologically differs considerably from all other members of the Chromatiaceae, including Trc. minor, the new isolate is described as a new species of the genus Thiorhodococcus, Thiorhodococcus drewsii sp. nov.

This is aside from the question of whether flagellum positioning is needed even in your average cell, e.g. it seems that E. coli does just fine by having several randomly-placed (or perhaps random but spaced-apart) peritrichous flagella.

A page describing the various ways flagella are distributed on bacteria.

Edited by niiicholas on Mar. 02 2003,21:06


Posts: 319
Joined: May 2002

(Permalink) Posted: Mar. 09 2003,20:01   

Jarrell and others have written a detailed review of prok. motility.  Very useful article.  


Microbiology 2003 Feb;149(Pt 2):295-304
Prokaryotic motility structures.

Bardy SL, Ng SY, Jarrell KF.

Department of Microbiology and Immunology, Queen's University, Kingston, ON, Canada K7L 3N6.

Prokaryotes use a wide variety of structures to facilitate motility. The majority of research to date has focused on swimming motility and the molecular architecture of the bacterial flagellum. While intriguing questions remain, especially concerning the specialized export system involved in flagellum assembly, for the most part the structural components and their location within the flagellum and function are now known. The same cannot be said of the other apparati including archaeal flagella, type IV pili, the junctional pore, ratchet structure and the contractile cytoskeleton used by a variety of organisms for motility. In these cases, many of the structural components have yet to be identified and the mechanism of action that results in motility is often still poorly understood. Research on the bacterial flagellum has greatly aided our understanding of not only motility but also protein secretion and genetic regulation systems. Continued study and understanding of all prokaryotic motility structures will provide a wealth of knowledge that is sure to extend beyond the bounds of prokaryotic movement.

PMID: 12624192 [PubMed - in process]


- They say the archaeal flagellum is powered by a proton gradient.  This contradicts my earlier thought which was that it was ATP-powered.  However, they cite no demonstration of the power source.  I would keep the question in mind, but here is what they say:

"The other major subdivision of prokaryotes is the domain Archaea. Members are motile via a structure that appears to be fundamentally distinct from the bacterial counterpart in composition and, likely, assembly (Thomas et al., 2001). The archaeal flagellum is a rotary structure, driven by a proton gradient, and it is thinner than typical bacterial flagella."

- A more detailed review of spirochete flagella which are weird.

- A nice review of current knowledge on the archaeal flagellum proteins, several identified similarities/homologies to type IV pilins...

- The archaeal flagellum probably/usually has hook and filament proteins, and they find at least a bit of evidence that the difference between the two is not so great:

"In archaea, there are always multiple (2–6) flagellin genes present (Sulfolobus solfataricus appears to be an exception). Thus far the only components of the archaeal flagellum identified are the flagellins themselves, where it appears that the multiple flagellins are all present as structural components of the assembled flagellum. Recent work indicated that the hook protein might in fact be a minor flagellin, FlaB3 in the case of Methanococcus voltae (Bardy et al., 2002) (Fig. 4)."

- Type IV pili movies (twitching motility etc.):
Type IV pili movies

- Ratchet structure review; it would be nice to know the genes involved, particularly if there is any rotary motion involved...

- Here's a whole new kind of motility, the contractile cytoskeleton (in a prokaryote)

Spiroplasma melliferum is one of the smallest free-living organisms on earth with a genome size about half that of E. coli. Surprisingly, this bacterium is motile, though nonflagellated, and it lacks any genes analogous to ones involved in flagellation as well as known gliding genes. This organism lacks a cell wall but has a membrane-bound internal cytoskeleton, composed primarily of a unique 59 kDa protein, which is thought to act as a linear motor, in contrast to the rotary motor of the flagellum (Trachtenberg, 1998) (Fig. 9). The cytoskeleton is attached to the cytoplasmic membrane, possibly through one or more of the approximately seven proteins that co-purify with it. The cytoskeleton is involved in motility due to its linear contraction and its close interaction with the cytoplasmic membrane (Trachtenberg & Gilad, 2001). The cytoskeleton exists as a seven fibril ribbon that extends the length of the cell. A conformational switch in the monomer leads to length changes: because of the strong interconnectiveness of the cytoskeleton subunits, changes in any part of the fibril are transmitted to neighbours and ultimately to the attached membrane. Though poorly studied at present, this motility structure represents a truly novel approach to motility using what appears to be a much smaller complement of genes than that required for flagellation. Identification of the roles of the cytoskeleton co-purifying proteins will be a major advance in the elucidation of this motility structure."

Conclusion: not much on evolution but good overview review.

While motility is commonplace among the prokaryotes, it is important to note the variety of structures responsible for motility. These structures vary depending not only on the organism in question, but also on the particular environment. Study of the bacterial flagellum has provided insights into many aspects of prokaryotic cellular activities including genetics and regulation, physiology, environmental sensing, protein secretion and assembly of complex structures. Continued study of all prokaryotic motility structures will provide knowledge that is likely to reach far beyond the topic of motility.


Posts: 319
Joined: May 2002

(Permalink) Posted: Mar. 21 2003,01:32   

A coupla recent flag-related articles, my summaries of evo-interesting bits in [].


Proc Natl Acad Sci U S A 2003 Mar 18;100(6):3027-30
Type III secretion systems and bacterial flagella: Insights into their function from structural similarities.

Blocker A, Komoriya K, Aizawa S.

Sir W. Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; and Department of Biosciences, Teikyo University, Utsunomiya 320-8551, Japan.

Type III secretion systems and bacterial flagella are broadly compared at the level of their genetic structure, morphology, regulation, and function, integrating structural information, to provide an overview of how they might function at a molecular level.


[More homologies to flagellar proteins than the standard ~9 or so: ]

Old and New Sequence Homologies.

TTS apparatuses are encoded by 25 genes (4), nearly all essential for function. About 10 TTSS proteins are similar in sequence or membrane topology to cytoplasmic or inner membrane proteins of flagellar hook-basal bodies (HBBs; refs. 5 and 6). Others show no significant sequence homology. However, they show "functional conservation" because when knocked out, they lead to similar phenotypes in assembly or function of the apparatuses. By matching biochemical characteristics and biological information about each protein (see Supporting Text, which is published as supporting information on the PNAS web site,, we propose the functional homologs shown in Fig. 1.

Morphological Similarities.

A part of the TTS machinery, the "needle complex" (NC) resembles HBBs (6, 7). NCs comprise a 10 × 60-nm external needle inserted within a 30-nm (in diameter) cylinder traversing both bacterial membranes and the peptidoglycan. The Shigella secreton has an additional "bulb," 45 × 25 nm, on the cytoplasmic side of the inner membrane, similar to the flagellar C-ring (refs. 8 and 9; Fig. 1). NCs are traversed by a 2- to 3-nm channel (10), which exists also within the entire bacterial flagellum (11). Flagellin may transit partially unfolded (12) through this channel to its tip, where it refolds and inserts into the growing filament (13, 14). Effectors from plant pathogen TTSSs are also secreted from the distal tip of their TTS machineries (15). During assembly of flagella in vivo, a cap is added before each transition to a new part of the flagellum so new subunits, which would otherwise diffuse away, can be inserted directly under the cap (16). NC components, including the needle component MxiH/PrgI, have been identified (17, 18). No cap has been identified in any TTSS. Morphological divergence between TTSSs is discussed in Supporting Text.


What are the energizers of posttranslational and cotranslational secretion?
The flagellar ATPase FliI is required for export of all flagellar proteins except the outer membrane components (5). Without it only the inner membrane and cytoplasmic components are assembled. Mutants in homologous TTSS ATPases display analogous phenotypes (65). Does cotranslational secretion occur by docking of the ribosome to the cytoplasmic part of the TTS machine like cotranslational export across the membrane of the endoplasmic reticulum? An empty flagellar C-ring could only accommodate two ribosomes, the protein channels of which could not directly dock to the HBB without a gap being left. Therefore, cotranslational secretion is probably also driven by the ATPase and hence indirect.

How is energy transduced by the export motor during secretion?
The ATPases interact with cytoplasmic components of TTSSs or flagella but the function(s) of these interactions are mostly unidentified (66, 67). The biological cycle of the enzyme is unknown and its localization is debated [cytosolic or membrane-bound (69)?]. How might these ATPases catalyze processive protein export? Spa47 (the Shigella FliI homolog) shares 33% amino acid identity with the -subunit of F1-ATPase. Proteins with >30% sequence identity have a high probability of sharing similar structures (69). Active F1-ATPase is a heterohexamer consisting of alternating - and -subunits with a -subunit inserted in a central channel where it rotates during the catalytic cycle (70). No equivalent of the -subunit of F1-ATPases is found within flagellar or TTSS-encoding operons, so we assume that the type III export motor is a homohexamer. When modeled on the F1 structure, Spa47 fits at the inner membrane base of our NC structure (Fig. 3). It would contain a central channel aligned with the one found within the NC and of similar diameter to it, through which the proteins could be secreted (see Supporting Text).

[It would be very interesting if the FliI ATPase really was a homohexamer like the F1 subunits in the F1F0 ATPase.  Not determinative of anything I suppose but it would make Rizzotti's model a bit more likely]



Our understanding of TTSSs was applied to obtain an MHC class I response against a heterologous translocated protein (75). TTSSs are targets for new antimicrobial drugs. Work on type IV secretion systems in other Gram-negative pathogens shows that they, too, can perform host cell contact-mediated protein translocation (76). Type IV secretion apparatuses resemble bacterial conjugation systems, which function differently from TTSSs. The sec-dependent secretion pathway of Gram-positive bacteria also seems capable of polarized protein translocation into host cells (77). These may be examples of convergent evolution.


Mol Cell Probes 2003 Feb;17(1):25-32
Detection of type III secretion genes as a general indicator of bacterial virulence.

Stuber K, Frey J, Burnens AP, Kuhnert P.

Institute of Veterinary Bacteriology, University of Bern, Langgassstrasse 122, CH-3012, Bern, Switzerland

Type III secretion systems of Gram-negative bacteria are specific export machineries for virulence factors which allow their translocation to eukaryotic cells. Since they correlate with bacterial pathogenicity, their presence is used as a general indicator of bacterial virulence. By comparing the genetic relationship of the major type III secretion systems we found the family of genes encoding the inner-membrane channel proteins represented by the Yersinia enterocolitica lcrD (synonym yscV) and its homologous genes from other species an ideal component for establishing a general detection approach for type III secretion systems. Based on the genes of the lcrD family we developed gene probes for Gram-negative human, animal and plant pathogens. The probes comprise lcrD from Y. enterocolitica, sepA from enteropathogenic Escherichia coli, invA from Salmonella typhimurium, mxiA from Shigella sonnei, as well as hrcV from Erwinia amylovora. In addition we included as a control probe the flhA gene from E. coli K-12 to validate our approach. FlhA is part of the flagellar export apparatus which shows a high degree of similarity with type III secretions systems, but is not involved in pathogenicity. The probes were evaluated by screening a series of pathogenic as well as non-pathogenic bacteria. The probes detected type III secretion in pathogens where such systems were either known or were expected to be present, whereas no positive hybridization signals could be found in non-pathogenic Gram-negative bacteria. Gram-positive bacteria were devoid of known type III secretion systems. No interference due to the genetic similarity between the type III secretion system and the flagellar export apparatus was observed. However, potential type III secretion systems could be detected in bacteria where no such systems have been described yet. The presented approach provides therefore a useful tool for the assessment of the virulence potential of bacterial isolates of human, animal and plant origin. Moreover, it is a powerful means for a first safety assessment of poorly characterized strains intended to be used in biotechnological applications.

[short version: no evidence of basal Type III secretion systems, but then this technique would probably only detect T3SS within the flagellum-derived-virulence-system "clade" anyhow...

Note that e.g. gram-positive bacteria have regular flagella, so when the authors say "Gram-positive bacteria were devoid of known type III secretion systems" they are not including flagella.]

Trends Cell Biol 2003 Mar;13(3):114-21
Rotary protein motors.

Oster G, Wang H.

Depts Molecular and Cellular Biology and ESPM, College of Natural Resources, University of California, 94720, Berkeley, CA, USA

THREE PROTEIN MOTORS HAVE BEEN UNAMBIGUOUSLY IDENTIFIED AS ROTARY ENGINES: the bacterial flagellar motor and the two motors that constitute ATP synthase (F(0)F(1) ATPase). Of these, the bacterial flagellar motor and F(0) motors derive their energy from a transmembrane ion-motive force, whereas the F(1) motor is driven by ATP hydrolysis. Here, we review the current understanding of how these protein motors convert their energy supply into a rotary torque.

[*two* motors in the F1F0 ATPase?  This is a different interpretation.  Anyhoo, no full-text access to this one for me.


J Mol Biol 2003 Mar 21;327(2):453-63
Ion-coupling Determinants of Na(+)-driven and H(+)-driven Flagellar Motors.

Asai Y, Yakushi T, Kawagishi I, Homma M.

Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-Ku, 464-8602, Nagoya, Japan

The bacterial flagellar motor is a tiny molecular machine that uses a transmembrane flux of H(+) or Na(+) ions to drive flagellar rotation. In proton-driven motors, the membrane proteins MotA and MotB interact via their transmembrane regions to form a proton channel. The sodium-driven motors that power the polar flagellum of Vibrio species contain homologs of MotA and MotB, called PomA and PomB. They require the unique proteins MotX and MotY. In this study, we investigated how ion selectivity is determined in proton and sodium motors. We found that Escherichia coli MotA/B restore motility in DeltapomAB Vibrio alginolyticus. Most hypermotile segregants isolated from this weakly motile strain contain mutations in motB. We constructed proteins in which segments of MotB were fused to complementary portions of PomB. A chimera joining the N terminus of PomB to the periplasmic C terminus of MotB (PotB7(E)) functioned with PomA as the stator of a sodium motor, with or without MotX/Y. This stator (PomA/PotB7(E)) supported sodium-driven motility in motA or motB E.coli cells, and the swimming speed was even higher than with the original stator of E.coli MotA/B. We conclude that the cytoplasmic and transmembrane domains of PomA/B are sufficient for sodium-driven motility. However, MotA expressed with a B subunit containing the N terminus of MotB fused to the periplasmic domain of PomB (MomB7(E)) supported sodium-driven motility in a MotX/Y-dependent fashion. Thus, although the periplasmic domain of PomB is not necessary for sodium-driven motility in a PomA/B motor, it can convert a MotA/B proton motor into a sodium motor.

[interesting bit of mixing and matching]


Posts: 319
Joined: May 2002

(Permalink) Posted: Mar. 31 2003,22:22   

Note that while flagella do not apparently make use of a secretin as the outer membrane pore, type III virulence systems do.  And furthermore, the outer membrane ring of the flagellum *is* secreted by a type II rather than Type III virulence system, an interesting similarity.

Other points here:
- 6+ secretion systems in one critter

- both type II and type III SS have virulent and non-virulent uses


Secretins of Pseudomonas aeruginosa: large holes in the outer membrane
Wilbert Bitter1

Abstract  Pseudomonas aeruginosa produces a large number of exoproteins, ranging from the ADP-ribosyltransferases exotoxin A and ExoS to degradative enzymes, such as elastase and chitinase. As it is a gram-negative bacterium, P. aeruginosa must be able to transport these exoproteins across both membranes of the cell envelope. In addition, also proteins that are part of cellular appendages, such as type IV pili and flagella, have to cross the cell envelope. Whereas the majority of the proteins transported across the inner membrane are dependent on the Sec channel, the systems for translocation across the outer membrane seem to be more diverse. Gram-negative bacteria have invented a number of different strategies during the course of evolution to achieve this goal. Although these transport machineries seem to be radically different, many of them actually depend on a member of the secretin protein family for their function. Recent results show that secretins form a large complex in the outer membrane, which constitutes the actual translocation channel. Understanding the working mechanism of this protein translocation channel could open up new strategies to target molecular machineries at the heart of many important virulence factors.
Keywords  Secretin - Outer membrane - Exoprotein - Pseudomonas aeruginosa - Pili


Secreted proteins of Pseudomonas aeruginosa
Gram-negative bacteria are efficiently protected against many harmful compounds in the environment by the presence of a second membrane, the outer membrane, which functions as a molecular sieve because of the presence of both specific and general pore-forming proteins (Hancock 1997). These porins form channels in the outer membrane through which small hydrophilic molecules with a molecular mass up to 250 Dalton can diffuse. However, gram-negative bacteria also have to transport a range of macromolecules across the outer membrane. Today, at least 19 different soluble exoproteins are known to be secreted by P. aeruginosa (Table 1). Most of these soluble exoproteins, such as exotoxin A, S, U and Y, elastase, staphylolytic protease, lipase and phospholipase C, are well-known virulence factors (Sandkvist 2001a; Cornelis and Van Gijsegem 2000), whereas others are at least suspected to be involved in virulence. This means that, among the gram-negative bacteria, P. aeruginosa is one of the most active secreting species. Proteins that are part of cellular appendages also have to be transported across the outer membrane. These compounds include the subunits that compose the flagella and the type IV pili. Both these appendages are used for binding and motility in P. aeruginosa and are essential for pathogenicity (Hahn 1997). Adhesins and surface-associated enzymes may also belong to this category.
All the proteins and protein structures described above have to be secreted through outer membrane channel(s). The opening of these channels will have to be strictly regulated in order to retain proper functioning of the outer membrane as a molecular sieve. In the last decade, it has become clear that there are multiple outer membrane channels and transport machineries for the translocation of proteins across this second membrane. If one only considers the soluble exoproteins, already six different pathways have been identified: the type I pathway (Andersen et al. 2000); the type II pathway (Filloux et al. 1998); the type III or contact secretion pathway (Cornelis and Van Gijsegem 2000); the type IV pathway (Christie 2001); the autotransporter pathway (Henderson et al. 1998); and the two-partner secretion pathway (Jacob-Dubuisson et al. 2001). Apart from the type IV secretion pathway, all of these different systems are used (Table 1) or are at least present in P. aeruginosa. In addition, chitinase is probably secreted via a novel pathway (Folders et al. 2001). Although there are many different transport systems, one family of outer membrane proteins has been shown to be particularly useful for P. aeruginosa, the secretins. Members of this family are involved in two of the secretion systems described above: the type II and the type III secretion pathways. These two systems seem to be completely different: the type III system mediates the secretion of virulence factors directly from the cytoplasm into eukaryotic target cells and is homologous to the flagellar assembly system, whereas the type II system secretes folded proteins from the periplasm into the surrounding and is highly homologous to the type IV pili biogenesis machinery. The only common denominator between these systems is the outer membrane component, which belongs to the secretin family (Genin and Boucher 1994). Secretin family members are also used for the biogenesis of type IV pili (Mattick et al. 1996), but not in flagella synthesis. In addition, secretins are involved in other processes, such as the biosynthesis of another class of pili (Skerker and Shapiro 2000) and the biogenesis of filamentous phage particles (Linderoth et al. 1997). These phages, such as Pseudomonas phage Pf3 and Escherichia coli phages M13 and f1, are continuously produced by infected bacterial cells without disrupting the integrity of the bacterial cell. Again, only the outer membrane component of this machinery shows homology with the other secretin-dependent secretion systems described above. Finally, in several other gram-negative bacteria, such as Haemophilus influenza and Neisseria species, secretin family members have been implicated in the process of natural competence, i.e. the uptake of DNA from the environment (Dubnau 1999). However, this dependence can be explained by the fact that, in these cases, type IV pili are involved in competence and secretin family members are essential components in the biosynthesis of this class of pili.

These data show that secretins are involved in many different processes in Proteobacteria. Recently, genome sequencing projects have demonstrated that secretins can also be found in a wide variety of other bacterial species, including such diverse species as Chlamydia trachomatis, Deinococcus radiodurans, and even the deep-branching species Aquifex aeolicus. This means that the use of secretins for outer membrane transport is widespread among the bacteria and that some of these new secretins could very well be involved in transport processes that have not been characterised thus far. What makes the secretin family members such useful proteins to be employed in protein transport? Part of the answer is probably related to the functional unit of secretins: the oligomeric complex.


Posts: 319
Joined: May 2002

(Permalink) Posted: April 05 2003,23:21   

Yet another kind of bacterial motility:


Mol Microbiol 2003 Feb;47(3):671-97

The bacterial linear motor of Spiroplasma melliferum BC3: from single molecules to swimming cells.

Spiroplasma melliferum BC3 are wall-less bacteria with internal cytoskeletons. Spiroplasma, Mycoplasma and Acholeplasma belong to the Mollicutes, which represent the smallest, simplest and minimal free-living and self-replicating forms of life. The Mollicutes are motile and chemotactic. Spiroplasma cells are, in addition, helical in shape. Based on data merging, obtained by video dark-field light microscopy of live, swimming helical Spiroplasma cells and by cryoelectron microscopy, unravelling the subcellular structure and molecular organization of the cytoskeleton, we propose a functional model in which the cytoskeleton also acts as a bacterial linear motor enabling and controlling both dynamic helicity and swimming. The cytoskeleton is a flat, monolayered ribbon constructed from seven contractile fibrils (generators) capable of changing their length differentially in a co-ordinated manner. The individual, flat, paired fibrils can be viewed as chains of tetramers approximately 100 A in diameter composed of 59 kDa monomers. The cytoskeletal ribbon is attached to the inner surface of the cell membrane (but is not an integral part of it) and follows the shortest helical line on the coiled cellular tube. We show that Spiroplasma cells can be regarded, at least in some states, as near-perfect dynamic helical tubes. Thus, the analysis of experimental data is reduced to a geometrical problem. The proposed model is based on simple structural elements and functional assumptions: rigid circular rings are threaded on a flexible, helical centreline. The rings maintain their circularity and normality to the centreline at all helical states. An array of peripheral, equidistant axial lines forms a regular cylindrical grid (membrane), by crossing the lines bounding the rings. The axial and peripheral spacing correspond to the tetramer diameter and fibril width (100 A) respectively. Based on electron microscopy data, we assign seven of the axial grid lines in the model to function as contractile generators. The generators are clustered along the shortest helical paths on the cellular coil. In the model, the shortest generator coincides with the shortest helical line. The rest, progressively longer, six generators follow to the right or to the left of the shortest generator in order to generate the maximal range of lengths. A rubbery membrane is stretched over (or represented by) the three-dimensional grid to form a continuous tube. Co-ordinated, differential length changes of the generators induce the membranal cylinder to coil and uncoil reversibly. The switch of helical sense requires equalization of the generators' length, forming a straight cylindrical tube with straight generators. The helical parameters of the cell population, obtained by light microscopy, constitute several subpopulations related, most probably, to cell size and age. The range of molecular dimensions in the active cytoskeleton inferred from light microscopy and modelling agrees with data obtained by direct measurements of subunit images on electron micrographs, scanning transmission electron microscopy (STEM) and diffraction analysis of isolated ribbons. Swimming motility and chemotactic responses are carried out by one or a combination of the following: (i) reciprocating helical extension and compression ('breathing';); (ii) propagation of a deformation (kink) along the helical path; (iii) propagation of a reversal of the helical sense along the cell body; and (iv) irregular flexing and twitching, which is functionally equivalent to standard bacterial tumbling. Here, we analyse in detail only the first case (from which all the rest are derived), including switching of the helical sense.

Omigod!  Yes another nonflagellar swimming system!!  That designer sure was a busybody!


My cursory thoughts:

1) This page on spiroplasma:
...says that sprioplasmas are related to gram-positive bacteria, and have no cell wall, have a cytoskeleton and membranes with cholesterol.  This all seems to go along fairly well with Cavalier-Smith's proposed scheme for the evolution of eukaryotes as something like:

gram-negative --> gram-positive --> early divergence from archaeabacteria --> eukaryotes

...even if this doesn't pan out it is an interesting bit of (vague) convergence.

2) I don't really even understand how the spiroplasma swimming works so speculating on evolution is pointless, however it sounds rather more like what Lynn Margulis thought spirochetes worked like when she proposed the spirochete-->eukaryotic cilium hypothesis.  I doubt that spiroplasma-->cilium has any prospects either but it is interesting.

3) Even so, the more ways there are to swim, the more it seems that Dembski has drawn the target around the arrow with the flagellum.


It was suggested that this is vaguely like spirochetes, but not really IMO.

Periplasmic flagella of spirochaetes

Perhaps the most unusual case of bacterial flagellation is
that of the spirochaetes. Here flagella are located in the
periplasm between the outer membrane sheath and cell
cylinder, subterminally attached to one end of the cell
cylinder (Fig. 3). The number of periplasmic flagella and
whether the flagella overlap at the centre of the cell varies among species (Li et al., 2000a). The flagella function by rotating within the periplasmic space. Unlike some other bacteria in which flagellation depends on environmental changes, the spirochaete periplasmic flagella are expressed throughout the cell’s life-cycle and are believed to have vital skeletal and motility functions (Li et al., 2000b; Motaleb et al., 2000). Due to their continuous presence, the complex regulatory controls observed for motility gene expression in many bacteria seem to be absent in at least certain spirochaetes.


Titanospirillum velox: A huge, speedy, sulfur-storing spirillum from Ebro Delta microbial mats

paper online at


Posts: 319
Joined: May 2002

(Permalink) Posted: May 05 2003,17:50   

Another Nelson debate:




This is way off topic but you've made a number of assertions that needs to be addressed. For example, you say that I leave out various homologies. But in fact, I don't, the homologies you cite strengthen the fact that there exist mini-IC systems that would require unselectable steps for any evolutionary pathway.

"Mini-IC systems?"  But I thought that IC meant that the *whole thing* was IC?  


For example, with regard to MotAB, the motor complex in the flagellum requires 3 components, fliG, motA, and motB, and this is analogous to the ICness of ExbB, ExbD, and TonB.

ExbB and ExbD act on TonB, IIRC there's another ExbBD pair homolog that acts on something else.  And motAB act on fliG in a similar fashion.  Which is why Kojima & Blair wrote in Biochemistry (2001, vol. 40, pp. 13041-50),

The occurrence of significant conformational change in the stator has implications not only for the present-day mechanism but also for the evolution of the flagellar motor. A membrane complex that undergoes proton-driven conformational changes could perform useful work in contexts other than (and simpler than) the flagellar motor, and ancestral forms of the MotA/MotB complex might have arisen independently of any part of the rotor.

Nelson continues,


Still, there are more problems with regard to the logistical operations needed to be performed by a stochastic process in order to make this thing work from an ion channel, as Mike points out:

Of all the ways to mutate an ion channel, the number of ways that would result in its interacting with the base of some filament is surely in the distinct minority. And of all the ways to mutate an ion channel that gloms onto a filament, the number of ways to mutate it such that rotation does not occur is probably much higher than the number of ways to elicit some rotation...

None of this is disputed, but all it is saying is that "beneficial mutations are unlikely" which is no surprise to evolutionary biology.  All that is needed is one rare beneficial mutation amongst millions of ones that "don't work" and selection will pick it out.  And, FWIW, mutation experiments seem to indicate that there is a fair bit of flexibility where motor function is retained despite mutation in the MotB--rotor interface.


This [mutation] allows some ion channel to glom onto the base of a filament and open its channel and expose the ion flow to the proto-rotor in such a way that a set of electrostatic interactions just happen to form and elicit significant rotation.

This depends upon a particular model of the mechanism of flagellar rotation, which is an unsolved question (Hey! A place for the IDer to act in modern times!  Unless you're a nasty methodological naturalist...).  Based on the ExbBD homology, I would expect that the ion channel is essentially internal to the ExbBD system and that the energy resulting from H+ flow is transferred through the protein structure via conformational change to act on the flagellum base (or on TolB etc.) to do work at a distance.  Call it a prediction if you like.  The electrostatic model certainly is elegant, but based on ExbBD homologs being independent units doing "work at a distance" in several different systems, it seems unlikely.  Time will tell.

The homology between FliI is said to only be homologous to the b subunit of the F-ATP synthase, not the whole 8 parts of the synthase, the whole thing requires all 8 parts to work.

IIRC the 3 alpha and 3 beta subunits of the F1 ATPase are thought to be homologs of each other, with only the beta subunits retaining ATPase activity:

The similarity of the beta subunit to FliI is something like 33% which is highly statistically significant, well above the ambiguous level:


How might these ATPases catalyze processive protein export? Spa47 (the Shigella FliI homolog) shares 33% amino acid identity with the beta-subunit of F1-ATPase. Proteins with >30% sequence identity have a high probability of sharing similar structures (69). Active F1-ATPase is a heterohexamer consisting of alternating alpha- and beta-subunits with a gamma-subunit inserted in a central channel where it rotates during the catalytic cycle (70). No equivalent of the alpha-subunit of F1-ATPases is found within flagellar or TTSS-encoding operons, so we assume that the type III export motor is a homohexamer. When modeled on the F1 structure, Spa47 fits at the inner membrane base of our NC structure (Fig. 3). It would contain a central channel aligned with the one found within the NC and of similar diameter to it, through which the proteins could be secreted (see Supporting Text).

Source: Blocker A, Komoriya K, Aizawa S. Proc Natl Acad Sci U S A 2003 Mar 18;100(6):3027-30. Type III secretion systems and bacterial flagella: Insights into their function from structural similarities.

...the assumption of homology seems to be confirmed by the fact that the resulting protein complex fits well into their model of T3SS structure.


With respect to the possibility that the rod proteins were derived from each other, Mike Gene addresses this in his essay:

It would seem there is no reason why the rod should be built around three proteins instead of simply one. Yet these three gene products are found in all flagella, dating back to the putative ancestral flagellum. This suggests one protein is not sufficient to form a functioning flagellar rod. Furthermore, the size of these proteins among these five distantly related bacteria has been held relatively constant (Fig 2), despite billions of years of experiencing very different selective pressures. It would seem some form of constraint or specification is at work, as natural selection will not tolerate too much deviation. And these size constraints map back to the last common ancestral flagellum, indistinguishable from the first flagellum.

It seems highly unlikely that the different rod proteins have radically different functions.  Probably their retention has to do with starting and stopping the rod construction process, wherein it would be helpful to have a tightly-controlled starting and stopping points, but where simpler mechanisms could suffice at first, e.g. just generating a certain amount of one rod protein.

All that is required to get from one rod protein to several is the sub-functionalization of gene copies, which you, Nelson, have enthusiastically endorsed in other threads.


Gram positive bacteria don't need the L and P rings because they simply do not have an outer membrane. I think that it's as simple as that (well not really, Mike has hinted at how this can illuminate something about it's origin but hasn't discussed this yet).

So, are they part of the IC system or not, and how many orders of magnitude difference in probability does this decision result in?


I'm not familiar with a flagellum serving as an adhesion organelle, although I'm familiar with pili that do.

An example (one of many) was cited in the original immune system thread.


With that you continue to introduce more unselectable steps, the irreducible complexity of the folding of P Pilus, not to mention the sophisticated mechanisms, donor strand exchange and donor strand complementation. The pilus itself is made up of 5 parts, PapK PapA,PapE,PapK, and PapG. Furthermore, the pilus doesn't seem to be able to secrete proteins, and the biggest difference between flagella and pili is that flagella are built from the top to the bottom, whereas pili are built from the bottom to the top. The notion of a simple filament sticking to an export machine seems to vanish.

Huh?  There are many kinds of pili, the term basically means "sticky-outy bit" as far as I can tell.  And it seems that basically every transport system that has been identified has versions that support extracellular extensions. They all have to secrete proteins, in order to get the pilus proteins to the outside.  You are focusing on the abilities of the P pilus, built on a Type I transporter IIRC, but we are talking about type III secretion systems.  It appears that flagella and pili can be built from the top or the bottom, since Type III and Type IV (both have motile flagella and nonmotile pili systems) do each respectively.


As far as the last two, I would need to see those for myself. I am cautious at Nic's constant mentioning of homology due to the fact that he doesn't take anything like convergence or coincidence (or common design) into account, which kind of makes me careful to accept his criteria for saying something is homologous. And as we have seen, structural homologies are not good indicators of common descent.

Sequence and structural homology are well-documented concepts with a great deal of predictive theory and evidence behind them.  "Common design" is the at-random invocation of "the designer would have put statistically significant but functionally pointless similarities in a phylogenetic pattern for no good reason" which is erected as a smoke screen to avoid dealing with the statistically significant but functionally unnecessary similarity.  

For the chemotaxis homologs, see this thread.  The similarites are in sequence, not just structure IIRC.

As for the secretin, the evidence is merely suggestive at this point: there is no statistical evidence of homology at this point AFAIK.  But it is interesting that the outer membrane ring of flagella is secreted by a type II rather than type III pathway, as is the secretin used in the outer membrane of type III virulence systems, as is the outer membrane secretin used in a large number of other transport systems (see: Bitter W., Secretins of Pseudomonas aeruginosa: large holes in the outer membrane. Arch Microbiol 2003 May;179(5):307-14).  If structural homology is discovered at some point, then another piece of the puzzle will have fallen into place.

Even here we are a far cry from Dembski's strawman of getting flagellum parts from the mythical, mystical "protein supermarket".


As Mike Gene states, as far as pores go, not any old pore would do. The logic of this is that with all the pores that exist, if things were that simple, we should see plasticity among flagella of eubacteria (indeed this is one of the major problems with co-option stories, no plasticity.)

I'm not sure what the logic is.  The point is not plasticity in eubacterial flagella (although there is some of that), the point should be that several different complex motility systems are based on several different transport systems.  Assuming that the eubacterial flagella was "the goal" is unwarranted (a form of "painting the target around the arrow"), because we have archaeal flagella, twitching motility, slime-secretion motility, and probably other systems.  It appears that something like half of the classes of secretion systems have the capability to be modified to make use of their "sticky-outy bits" for motility.  Evolutionary theory doesn't need to postulate that "any old pore" would do, just that there are a lot of different pores, and that some of them would do.

Woese is a different topic so I won't address that.


Posts: 319
Joined: May 2002

(Permalink) Posted: May 06 2003,16:00   

Yet another reply for the archive:

[A brief aside: Nelson, your sentences often run-on and seem rather breathless.  This makes them difficult to interpret sometimes.  Just a heads-up...]

Regarding the mechanism of flagellar rotation, Nelson really should have read Kojima and Blair's 2001 paper before citing older papers in favor of Nelson/Mike Gene's favored model:


With respect to electrostatic interaction, I don't think we can say that the channel is internal to ExbBD. TonB might function in opening the channel or causing some kind of structural change. ExbB has only 3 membrane segments as opposed to MotA which has four.

The electrostatic model of the bacterial flagellar motor seems to be a bit more then a hunch, in fact, that electrostatic model behind flagella rotation seems to be near certainty that it is correct:

Bren, Anat and Michael Eisenbach. "How Signals Are Heard during Bacterial Chemotaxis: Protein-Protein Interactions in Sensory Signal Propagation." Journal of Bacteriology. 182:6865-6873 (2000).

I think even Blair, the author of the paper you cite for the ExbBD complex has done some work on this:

Zhou, J.D., Lloyd, S.A., and Blair. D.F. (1998) Electrostatic interactions between rotor and stator in the bacterial flagellar motor. Proc. Natl. Acad. Sci. USA 95, 6436-6441

Mutational studies of the rotor protein FliG and the stator protein MotA showed that both proteins contain charged residues essential for motor rotation. This suggests that functionally important electrostatic interactions might occur between the rotor and stator.

So it may not even matter that MotAB is homologous to ExbBD, if the electrostatic interactions are completely essential. Thus, I think Mike's objection should be taken seriously here with respect to the logistical problems with random mutations and ion channels.

LOL!  Virtually everything you argue ("near certainty" that the electrostatic model is correct, the channel is not internal to MotAB) is contradicted by the very Kojima and Blair article I've been citing.

Kojima and Blair write that based on the results of their 2001 paper, they think that the proton channel is internal and that the MotAB conformational-change model is probably correct:


In the years since the discovery of flagellar rotation, many hypotheses for the mechanism have been proposed (reviewed in ref 43). The models are diverse, but can be classified according to whether the proton pathway includes elements of both the rotor and stator or is confined to just the stator (Figure 1). Because the mutational studies found no critical titratable residues on the rotor, we currently favor models in which protons remain within the stator. In this case, proton flow must be coupled to rotation by some means other than direct proton-rotor contact. Our hypothesis is that protonation of Asp32 in MotB drives conformational changes in the stator, which work on the rotor to drive rotation.


Here, we test for conformational changes in the MotA/MotB complex by using limited proteolysis. Patterns of proteolysis of MotA were compared in wild-type MotA/MotB complexes and complexes with mutations in key residues of one or both of the proteins. The results support a mechanism in which the stator undergoes significant changes in conformation. [bold added]
Indeed, the separability of the motor as an independent subunit appears to be what led them to look this is what led them to look for independently-functioning homologs in simpler contexts:


The occurrence of significant conformational change in the stator has implications not only for the present-day mechanism but also for the evolution of the flagellar motor. A membrane complex that undergoes proton-driven conformational changes could perform useful work in contexts other than (and simpler than) the flagellar motor, and ancestral forms of the MotA/MotB complex might have arisen independently of any part of the rotor. We queried the sequence database using the sequence of the best-conserved part of MotA (the segment containing membrane segments 3 and 4) from Aquifex aeolicus, a species whose lineage is deeply branched from other bacteria. In addition to the expected MotA homologues, the search returned a protein sequence from the archaeal species Methanobacterium thermoautotrophicum (protein MTH1022) that shows significant sequence similarity not only to MotA but also to the protein ExbB (Figure 9).

As for mutational flexibility:


Residues of MotA that are important for function include two charged residues in the cytoplasmic domain, Arg90 and Glu98, that interact with the functionally important charged residues of FliG (39, 40). Like the charged residues of FliG, Arg90 and Glu98 of MotA function redundantly, and charge appears to be their key property. Two Pro residues of MotA located at the cytoplasmic ends of membrane segments, Pro173 and Pro222, are also important for rotation and might function to regulate conformational changes occurring during the torque-generating cycle (41). In MotB, an aspartic acid residue near the cytoplasmic end of the membrane segment, Asp32, is conserved and critical for motor rotation. A survey of conserved residues in MotA, MotB, FliG, FliM, and FliN found that no other titratable residue is critical for motor rotation (42). Asp32 is likely to have a direct role in the conduction of protons.
It appears that, basically, you need the Asp32 to transfer the proton through the channel internal to MotA/B, and then a significant variety of charged residues on the C-ring (FliG/M/N) and MotA can transfer the conformational change in MotA to "push on" the C-ring.  This seems rather less daunting than Mike Gene's characterization which you quoted:


Of all the ways to mutate an ion channel, the number of ways that would result in its interacting with the base of some filament is surely in the distinct minority. And of all the ways to mutate an ion channel that gloms onto a filament, the number of ways to mutate it such that rotation does not occur is probably much higher than the number of ways to elicit some rotation...This [mutation] allows some ion channel to glom onto the base of a filament and open its channel and expose the ion flow to the proto-rotor in such a way that a set of electrostatic interactions just happen to form and elicit significant rotation. Suffice it to say that such an improbable mutation has never been observed in nature or the lab.
This is not the only place where Kojima and Blair tripped up Mike Gene, indeed, he was originally skeptical of the existence of nonflagellar MotAB homologs:

MotA/MotB, on the other hand, could plausibly exist as some ion channel prior to the existence of the flagella, but there is no evidence of this.

I'll address the other points when I have time.  Like I said, why should we take your probability calculation seriously, when it is based on incorrect assumptions about the mechanism of rotation, the independence of the MotAB complex homologs, etc.?  Why doesn't your calculation include the possibility of cooption of MotAB from a pre-existing, simpler system?  Why does your calculation assume that proteins are drawn at random from a mythical "protein supermarket" when we have reasonable hypotheses for the prior functions of many of these proteins, and we have a large body of empirical evidence for the efficacy of natural processes to produce new genes by cooption and modification of old genes?

Edited by niiicholas on May 06 2003,16:03


Posts: 319
Joined: May 2002

(Permalink) Posted: May 07 2003,05:15   

Another reply from here:

Nelson writes,


With respect to adhesion organelles, I dont have time to tread though an entire thread to find an example of a flagellum acting as an adhesion organelle, but something tells me that you are just talking about a pilus, which I already discussed. My reason for thinking this is that since this was brought up in the immunity thread, PapD of the pilus has Ig-like domains. It is misleading to call pilus "bacterial flagellum".

I'm not sure what you're talking about with a pilus, although a great many (most?) pili of various kinds do have adherence as their function or one of their functions.

My point is that it appears many flagella also have an adhesion function.  The paper I was referring to from the immune system thread was the first paper I cited on page 1, sorry that wasn't clear:

Giron JA, Torres AG, Freer E, Kaper JB. The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial cells. Mol Microbiol 2002 Apr;44(2):361-79

There are others, e.g.:

Gavin R, Rabaan AA, Merino S, Tomas JM, Gryllos I, Shaw JG. Lateral flagella of Aeromonas species are essential for epithelial cell adherence and biofilm formation. Mol Microbiol. 2002 Jan;43(2):383-97  

One more:

de Oliveira-Garcia D, Dall'Agnol M, Rosales M, Azzuz ACGS, Martinez MB, Girón JA (2002).Characterization of Flagella Produced by Clinical Strains of Stenotrophomonas maltophilia. Emerging Infectious Diseases [serial online]


Although adherence to abiotic surfaces is a property of both environmental and clinical S. maltophilia isolates, little information has been available to elucidate the nature of the surface factors involved in this phenomenon. Flagella have been associated with biofilm formation in other bacteria (18,20–22), where they can perform three basic roles: a) act as an adhesin promoting intimate attachment to the surface; b) generate force to subjugate the repulsive forces between bacteria and surface; and c) promote spread of the bacteria throughout the surface (20).

I bring it up because the question is whether or not intermediate stages had selectable function.  It appears that an adhesive pili is one example of such a selectable intermediate stage, even though it wouldn't need motors or motility function.  

Based on the above quote, we might even put forward a hypothesis: a certain species of bacteria living in a pre-flagella world makes its living by adhering to particles (bits of silt or whatever).  When it reproduces, brownian motion spreads it a small distance in a random direction before it grows its primitive Type III pili and adheres to another silt particle.  Occasional disturbances (such as waves or tides or new silt layers) wipe out most of the population at regular intervals, creating a classic early-successional ecological system (think weeds in a continually disturbed field).

Amongst the typical huge number of detrimental mutations that go nowhere in this population, a very small proportion of the mutations cause a member of the population to have a mutant ExbB homolog that attaches to the base of the pili rather than whatever it was originally attached to.  This serves only to give random, undirected motion.  However, experiments even with bacteria with partially-disabled flagella or flagella stuck on "tumble" show that they have diffusion coefficients orders of magnitude higher than dead or otherwise immotile bacteria (which still have diffusion coefficients large relative to body size).  So, even undirected motility will serve to increase diffusion-distance-before-sticking, allowing that genotype to spread further and faster than the rest of the population (mechanisms to increase random diffusion of offspring are ubiquitous in life BTW, think dandelion seeds and go from there).  Thus, this mutation comes to dominate and we have our very primitive proto-flagellum.  Only gradually does all the fancy stuff get added -- finer co-adaptation of rotor and motor, chemotaxis sensors, switching, hook/flagellin distinction, etc.

Hmm, don't think that Dembski took anything like this into account in his calculation.


Posts: 319
Joined: May 2002

(Permalink) Posted: May 07 2003,19:21   

Some spiffy tools from online databases:

Species distribution for MotA_ExbB:

Entry for FliG, C-terminal domain:


Posts: 319
Joined: May 2002

(Permalink) Posted: May 08 2003,04:37


Crit Rev Microbiol 1996;22(2):67-100

Functions of bacterial flagella.

Moens S, Vanderleyden J.

F. A. Janssens Laboratory of Genetics, Katholieke Universiteit Leuven, Heverlee, Belgium.

Many bacterial species are motile by means of flagella. The structure and implantation of flagella seems related to the specific environments the cells live in. In some cases, the bacteria even adapt their flagellation pattern in response to the environmental conditions they encounter. Swarming cell differentiation is a remarkable example of this phenomenon. Flagella seem to have more functions than providing motility alone. For many pathogenic species, studies have been performed on the contribution of flagella to the virulence, but the result is not clear in all cases. Flagella are generally accepted as being important virulence factors, and expression and repression of flagellation and virulence have in several cases been shown to be linked. Providing motility is always an important feature of flagella of pathogenic bacteria, but adhesive and other properties also have been attributed to these flagella. In nonpathogenic bacterial colonization, flagella are important locomotive and adhesive organelles as well. In several cases where competition between several bacterial species exists, motility by means of flagella is shown to provide a specific advantage for a bacterium. This review gives an overview of studies that have been performed on the significance of flagellation in a wide variety of processes where flagellated bacteria are involved.


Posts: 319
Joined: May 2002

(Permalink) Posted: May 08 2003,04:58   



With respect to adhesion function, none of the papers show anything different from what I already discussed. In each paper, they talk about the export machine of bacterial flagellum, or pilus.

I don't understand what you are saying here at all.  Here is the point: non-motile cell extensions have function even though they are non-motile.  Some flagella still perform this function in addition to having their motility function.  This function remains even if they have no motors.


In both cases, we still have the "sea of nonfunctionality" that Dembski's calculation refers to. This is true, even if there are alternative functions all the way to the flagellum

This must set another record for self-contradiction!  If there are alternative functions "all the way to the flagellum" then the "sea of nonfunctionality" either doesn't exist or is crossed by a land bridge.


, each alternative function obviously requires several parts to function

So?  They function independently from being flagella, that is the point.  Dembski's calculation, like basically all antievolutionary calculations, assume that everything had to come together at once, in one step.  This is how ridiculously low probabilities are reached in calculations.


so you doing nothing more then what H. Allen Orr objected to:

This is the one quote that you have saying that cooption is unlikely, and it's not even clear what is meant as he's never expanded on these words, discussed the literature on cooption in detail, etc.  Orr himself refers to the change-of-function between swim bladders and lungs in that very review, which sounds to me rather like "half your car's transmission will suddenly help out in the airbag department."  And even if Orr meant exactly what you think he meant, I can cite dozens of other scientists of equal authority who think that cooption is indeed common, because they have written numerous articles and amassed a lot of evidence in favor of it.  For example:

The Origin of "Information" via natural causes

[url=]The Origin of "Information" via natural causes -- citations in the literature[/url]

Co-option/change of function -- Citations of this in the literature

Origins of morphological novelty


For example, you have the problem of the 6 part export machine. There is no evidence that any subset of this export machine carries out alternative function. And as I stated with the pili, With that you continue to introduce more unselectable steps, the irreducible complexity of the folding of P Pilus, not to mention the sophisticated mechanisms, donor strand exchange and donor strand complementation. The pilus itself is made up of 5 parts, PapK PapA,PapE,PapK, and PapG.

There are lots of kinds of pili based on lots of kinds of transport systems, you keep bringing up  one specialized system (based on a Type I transporter) over and over like it was some kind of talisman.  Type III virulence systems (called Type III pili in some articles, like this the Cornelius and Van Gijsegem paper mentioned earlier).  

It's not very clear, but by repeated mention of the P pilus I assume that you are trying to argue that a pili extension, excluding the export system at the base, would *have* to be made of at least 5 parts in order to function.  But there is no "logic of pili" that requires this -- while a rotary motor must, logically, have at least a stator, rotor, and filament, a simple pili could really be made of one repeated subunit.  Figure 1B of Blocker et al. 2003 (Pubmed) depicts a generalized T3SS where the extracellular extension (pili) is made up of MxiH/PrgI (homologs in 2 different organisms) for the entire stalk and "CaoX?" at the tip, perhaps a cap and/or adhesion protein at the tip (flagellar cap proteins are known to have adhesive functions in some bacteria, if you were interested).  The article says that it is not even clear that T3SS require a cap protein as none has yet been detected.  The online supporing text says that only some T3SS bother to add an additional filament to the top of the needle.

Furthermore, the pilus doesn't seem to be able to secrete proteins, and the biggest difference between flagella and pili is that flagella are built from the top to the bottom, whereas pili are built from the bottom to the top.

But of course Type III pili secrete just fine out the top.  And archaeal flagella are built from the bottom like some pili.  So there is no problem for pili to secret or be built at the top and no problem for flagella to be built from the base.  I recall pointing this out before in this very thread, but you bring up the argument again as if you didn't have to address the counterargument.


Now you keep saying things like "I wonder why Dembski didn't take that into account". Now, can you show, in the peer reviewed literature, a paper that shows how natural selection and random mutation, taking all those imaginary homologs and multi-part machines into account with alternative functions, a detailed pathway leading up to the flagellum that Dembski could have worked with. What do we find in the peer reviewed literature?

Dembski hasn't even dealt with the implications of the "imaginary" homologs published in Kojima and Blair, with direct commentary on evolutionary implications, in Biochemistry in 2001.  But Dembski, and you, are arguing that his calculation "sweeps the field clear" of natural hypotheses and that therefore design is the logical conclusion.  This is far more ambitious than simply pointing out that the literature does not yet contain the evolutionary pathway for every molecular system whose mere structure and function have yet to be fully understood.

Even where there is extensive peer-reviewed literature on the evolution of an IC system, e.g. the entire field of evolutionary immunology, neither you nor Dembski has shown any respect for it, despite your respective wild assertions about there being no literature on the evolution of IC systems.

And, no one ever published Dembski's straw-man "the flagellum assembled all at once" model, and yet you and Dembski are treating it as if it's the only conceivable route for natural processes to take.


We find the evidence that type III systems evolved from the flagellum, and there are good reasons for this. Even taking all these similarities into account, it is quite easy to see how the "sea of nonfunctinality" between each mutli-part machine (especially when proposing a sticky-out thing when in fact it would be useless in a "brownian storm", again the question of minimal function where the actual components don't even matter, it's what those components can do),

Well, I already told you about the diffusion coefficient difference between dead bacteria and bacteria stuck on "tumble" with completely undirected motility, but I guess you won't believe me unless I give you the numbers.  From Berg, 1993, Random Walks in Biology, p. 93:

Diffusion coefficient of a bacterium with flagellum stuck on "run" (rotation is only due to Brownian motion): 2 x 10^-5 cm2/sec

Diffusion coefficient of a normal E.coli bacterium with flagellum doing "run" and "tumble" at normal proportions: 4 x 10^-6 cm2/sec (however, the normal bacterium can bias runs in the right direction to be longer, leading to directional drift, i.e. chemotaxis).

Diffusion coefficient of a bacterium with flagellum stuck on "tumble" is described as "smaller" and that of a dead or paralyzed bacterium it is described as "much smaller".  The number calculated for the dead/paralyzed bacterium is 2 x 10^-9 cm2/sec, so a "stuck on tumble" bacterium is above this but below the number for the non-chemotactic "stuck on run" bacterium.

Even undirected motility, even in a non-smooth-run fashion, appears to improved dispersal capability quite a bit.


[...] most likely none of these alternative machines will confer a selective advantage until we arrive at the fully functional flagellum. Pure chance events come in full force when you attempt to fortitously have multi-part machines interacting with multi-part machines. It's nothing but a tornado in a junk yard.

No, Dembski's calculation is like assembling a plane by putting a tornado in a junkyard.  But no one advocates that model.  What evolution proposes is (vaguely) more like a "tornado" coming through a junkyard and making various modifications to parts, sometimes linking two systems in some way.  True, most of these go nowhere, but the occasional pairing that is successful can be selected and therefore will persist for another bunch of rounds of modifications and selection, which may eventually successfully pair one double system with another system of one or more parts, etc.  The analogy still sucks but this gives some idea of how many important factors Dembski's random-assembly-all-at-once calculation leaves out.


Posts: 319
Joined: May 2002

(Permalink) Posted: May 15 2003,15:38   

A Gonzaga student writes,

CONTINUED, AN ARISTOTELIAN DEFENSE ... ...based in part on the bacterial flagellum.


Purcell, Edward M.
The efficiency of propulsion by a rotating flagellum

An important note:

The original version of this manuscript was completed by E.M.P. on April 26, 1978. It is an elaboration of thoughts presented in figures 13 and 14 of ‘‘Life at low Reynolds number’’ (1). A later version of the manuscript dated October 5, 1992, included an appendix in which E.M.P. worked out the propulsion efficiency of a rotating helical cylinder connected to a sphere (i.e., the power required to drag the sphere through a viscous medium, derived
from Stokes law, divided by the power expended by the flagellar rotary motor). That work is not included here, because a similar calculation has been given by Childress (2). E.M.P. concluded that if the ratio of the viscous drag on a thin cylinder moving sideways at a
given velocity to the viscous drag on the cylinder moving at the same velocity lengthwise were ‘‘a 5 2, which it is supposed to be . . . the propulsion efficiency cannot exceed 3% under any circumstances.’’ With more realistic values, he estimated a maximum of 1.7%.

Also by Purcell:

Life at Low Reynolds Number

Relevant to efficiency claims:


When you put all this in and calculate the efficiency, you find that it's really rather low even when the various parameters of the model are optimized. For a sphere which is driven by one of these helical propellers (Fig. 16), I will define the efficiency as the ratio of the work that I would have to do just to putt that thing along to what the man inside it turning the crank has to do. And that turns out to be about 1%. I worried about that result for a while and tried to get Howard interested in it. He didn't pay much attention to it, and he shouldn't have, because it turns out that efficiency is really not the primary problem of the animal's motion. We'll see that when we look at the energy requirement. How much power does it take to run one of these things with a 1% efficient propulsion system, at this speed in these conditions? We can work it out very easily. Going 30 micron/sec, at 1% efficiency will cost us about 2\times 10^{-8} ergs/sec at the motor. On a per weight basis, that's a 0.5 W/kg, which is really not very much. Just moving things around in out transportation system, we use energy at 30 or 40 times that rate. This bug runs 24 hours a day and only uses 0.5 W/kg. That's a small fraction of its metabolism and energy budget. Unlike us, they do not squander their energy budget just moving themselves around. So they don't care whether they have a 1% efficient flagellum or a 2% efficient flagellum. It doesn't really make that much difference. They're driving a Datsun in Saudi Arabia.


Posts: 319
Joined: May 2002

(Permalink) Posted: May 27 2003,22:50   

Reposting from II thread:

The author (Robin Holliday) does mention the flagellum; unfortunately s/he just kinda brushes it off:


Since the wheel has become so important for human motility and diverse other purposes, one would think that it might also be used by animals in a variety of contexts. It could be argued that the wheel can only be used effectively on smooth surfaces, and these are uncommon in nature. However, that is not true because there are salt and dry mud flats, hard damp sand on beaches, leaves and the barkof some trees. Moreover, man-made vehicles can cover rough ground very effectively. The fact of the matter is that the wheel is not found anywhere in the animal kingdom. The nearest is in the tiny rotifer, where the feeding structures appear to rotate. This is an illusion brought about be the movement of a circle of attached cilia slightly out of synchrony to create a vortex that draws water and food into the animal. The flagellae of motile bacteria that have a rotary propeller-like movement contain a single structural protein called flagellin, but could scarcely be regarded as wheel-like. However, the principle of jet propulsion is used by certain marine animals, notably the squids and octopuses, but no propellers as such are found in any aquatic multicellular organism. So how do the creationists explain why an all-powerful deity did not on any occasion design an animal incorporating the enormously advantageous rotary motion of wheels?

I think that the flagellum (and other rotary motors, e.g. the F1F0 ATPase, archaeal flagellum) are indeed valid exceptions to the "evolution can't make wheels" argument.  One might quibble that "rolling" and "spinning" aren't really valid concepts at the microscopic scale where Brownian motion is so crucial -- the "rotation" is jerky and there is no such thing as inertia -- but, to me, a rotating machine is a rotating machine.

Note that this wheel argument is old, dating at least back to Haldane (assuming the cite is right), and has been turned on the evolutionists by creos:


Design in Living Organisms: Motors
by Jonathan Sarfati
Creation Ex Nihilo Technical Journal 12(1):3–5, 1998

Would any evidence convince evolutionists?

The famous British evolutionist (and communist) J.B.S. Haldane claimed in 1949 that evolution could never produce ‘various mechanisms, such as the wheel and magnet, which would be useless till fairly perfect.’ [10] Therefore such machines in organisms would, in his opinion, prove evolution false. These molecular motors have indeed fulfilled one of Haldane’s criteria. Also, turtles [11] and monarch butterflies [12] which use magnetic sensors for navigation fulfil Haldane’s other criterion. I wonder whether Haldane would have had a change of heart if he had been alive to see these discoveries. Many evolutionists rule out intelligent design a priori, so the evidence, overwhelming as it is, would probably have no effect.


10. Dewar, D., Davies, L.M. and Haldane, J.B.S., 1949. Is Evolution a Myth? A Debate between D. Dewar and L.M. Davies vs. J.B.S. Haldane, Watts & Co. Ltd / Paternoster Press, London, p. 90.

11. Sarfati, J.D., 1997. Turtles can read magnetic maps.

12. Poirier, J.H., 1997. The Magnificent Migrating Monarch. Creation Ex Nihilo 20(1):28–31 (see online version). But monarchs only use the earth’s magnetic field to give them the general direction, while they rely on the sun’s position for most of their navigation.

Other sites using the same quote:


The World's Tiniest Motor

I could swear that there is another longer quote out there, from Haldane or another evolutionist, but I can't find it.  

(Does anyone have access to the Haldane-creo debate book, Is Evolution a Myth? -- it would be great to have a fuller quote)

Anyhow, you could hardly blame the creationists for pouncing on this one if everyone took the dismissive line that Holliday did on the evolution of wheels.  Unfortunately for them, Dawkins already noted the crucial difference between evolving wheels at the macro-scale and the subcellular scale:


Why don’t animals have wheels?
by Richard Dawkins
Article in The Sunday Times,  November 24th 1996


Now I must mention that there is one revealing exception to my premiss.  Some very small creatures have evolved the wheel in the fullest sense of the word.  One of the first locomotor devices ever evolved may have been the wheel, given that for most of its first two billion years, life consisted of nothing but bacteria (and, to this day, not only are most individual organisms bacteria, even in our own bodies bacterial cells greatly outnumber our ‘own’ cells).

Many bacteria swim using threadlike spiral propellors, each driven by its own continuously rotating propellor shaft.  It used to be thought that these ‘flagella’ were wagged like tails, the appearance of spiral rotation resulting from a wave of motion passing along the length of the flagellum, as in a wriggling snake.  The truth is much more remarkable.  The bacterial flagellum is attached to a shaft which, driven by a tiny molecular engine, rotates freely and indefinitely in a hole that runs through the cell wall.

Picture (see suggestions faxed separately to Jeremy Bayston)

The fact that only very small creatures have evolved the wheel suggests what may be the most plausible reason why larger creatures have not.  It’s a rather mundane, practical reason, but it is nonetheless important.  A large creature would need large wheels which, unlike manmade wheels, would  have to grow in situ rather than being separately fashioned out of dead materials and then mounted.  For a large, living organ, growth in situ demands blood or something equivalent.  The problem of supplying a freely rotating organ with blood vessels (not to mention nerves) that don’t tie themselves in knots is too vivid to need spelling out!

Human engineers might suggest running concentric ducts to carry blood through the middle of the axle into the middle of the wheel.  But what would the evolutionary intermediates have looked like?  Evolutionary improvement is like climbing a mountain (“Mount Improbable”).  You can’t jump from the bottom of a cliff to the top in a single leap. Sudden, precipitous change is an option for engineers, but in wild nature the summit of Mount Improbable can be reached only if a gradual ramp upwards from a given starting point can be found.  The wheel may be one of those cases where the engineering solution can be seen in plain view, yet be unattainable in evolution because its lies the other side of a deep valley, cutting unbridgeably across the massif of Mount Improbable.

The wheel may be one of those cases where the engineering solution can be seen in plain view, yet be unattainable in evolution because it lies the other side of a deep valley, cutting unbridgeably across the massif of Mount Improbable.

(Why don't we have articles like this in the newspapers in the U.S.?  Oh well...)

Still, Dawkins offers no evidence that the flagellum evolved, so this is still likely to be thoroughly undaunting to the creationist. Here in 2003 we are in a somewhat better position:

an AE thread collecting relevant info/links on the evolution of prokaryote flagella

Edited by niiicholas on May 27 2003,23:07

  46 replies since Nov. 28 2002,22:50 < Next Oldest | Next Newest >  

Pages: (2) < [1] 2 >   

Track this topic Email this topic Print this topic

[ Read the Board Rules ] | [Useful Links] | [Evolving Designs]