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+---Topic: Co-option/change of function started by niiicholas
Posted by: niiicholas on June 11 2002,00:44
This thread is for accumulating examples of cooption/change of function from the literature, and citations of the importance of this process in the literature.
The purpose of examining this is that Behe and Dembski both fail to give cooption the attention it absolutely deserves. In particular the occurence of cooption disproves Behe's IC argument.
Posted by: niiicholas on June 11 2002,01:03
I was struck by this passage from Maynard Smith's The Theory of Evolution. It almost sounds like it was written to respond to Behe, except that it was written in 1958 (I think; I have the 1993 Canto edition which is the fourth edition):
Discussing the origin of feathers, Maynard Smith writes (pp. 303-304):
This example will help to explain one of the difficulties often encountered in explaining evolution in terms of natural selection. It often seems that a perfected organ, although efficient at performing its function, is far too complex to have arisen by one or a few mutations, and yet is such that any intermediate stage between the absence of the organ and its full development would be incapable of performing this function. Thus it is inconceivable that the flight feathers of a bird could have arisen by a single mutation, but the intermediate stages between a scale and a feather would be useless for flight. In this case the difficulty disappears once it is realized that during the early stages of the evolution of feathers, the latter were probably of selective advantage because they conserved heat, and only later did they become functional in flight.
This is a very common feature of evolution; a new structure evolves at first because it confers advantage by performing one function, but in time it reaches a threshold beyond which it can effectively perform a different function. We saw earlier that something of this kind occurred during the evolution of the elephant's trunk. The flying membranes of bats and of pterodactyls were probably used in gliding before they were of any use in flapping flight, and, as Spurway has pointed out, small membranes along the sides of the body are found in some arboreal mammals which do not even glide, and these folds of skin render such animals more difficult to see by eliminating the shadows they would otherwise case. Similarly, lungs were a selective advantage to fish living in stagnant waters, enabling them to breathe air, long before the descendants of these fish walked on land; in modern teleost fishes the lung has lost its function as a breathing organ, and has been transformed into a hydrostatic organ, the swim bladder. These examples show that there is no reason to suppose that even the most complex structures underwent a long period of evolution and elaboration before they could function, and so confer selective advantage; rather their function may have changed once or even several times in the course of evolution.
This long-standing hypothesis regarding the origin of feathers has been strengthened by recent discoveries of fossil dinosaurs with non-flight feathers. E.g. the fantastic pictures here:
< http://research.amnh.org/vertpaleo/dinobird.html >
Posted by: niiicholas on June 11 2002,01:24
Found this key Darwin quote on the ISCID forum:
Chapter 6 of Origin of Species
Here is the link:
< http://www.talkorigins.org/faqs/origin/chapter6.html >
Note especially how closely Darwin ties the change-of-function argument to his "organs of extreme perfection" line which is so often quoted by antievolutionists. Why don't they ever acknowledge that Darwin himself listed numerous cases of homologous structures being adapted for wildly different functions?
If it could be demonstrated that any complex organ existed, which could not possibly have been formed by numerous, successive, slight modifications, my theory would absolutely break down. But I can find out no such case. No doubt many organs exist of which we do not know the transitional grades, more especially if we look to much-isolated species, round which, according to my theory, there has been much extinction. Or again, if we look to an organ common to all the members of a large class, for in this latter case the organ must have been first formed at an extremely remote period, since which all the many members of the class have been developed; and in order to discover the early transitional grades through which the organ has passed, we should have to look to very ancient ancestral forms, long since become extinct.
We should be extremely cautious in concluding that an organ could not have been formed by transitional gradations of some kind. Numerous cases could be given amongst the lower animals of the same organ performing at the same time wholly distinct functions; thus the alimentary canal respires, digests, and excretes in the larva of the dragon-fly and in the fish Cobites. In the Hydra, the animal may be turned inside out, and the exterior surface will then digest and the stomach respire. In such cases natural selection might easily specialise, if any advantage were thus gained, a part or organ, which had performed two functions, for one function alone, and thus wholly change its nature by insensible steps. Two distinct organs sometimes perform simultaneously the same function in the same individual; to give one instance, there are fish with gills or branchiae that breathe the air dissolved in the water, at the same time that they breathe free air in their swimbladders, this latter organ having a ductus pneumaticus for its supply, and being divided by highly vascular partitions. In these cases, one of the two organs might with ease be modified and perfected so as to perform all the work by itself, being aided during the process of modification by the other organ; and then this other organ might be modified for some other and quite distinct purpose, or be quite obliterated.
The illustration of the swimbladder in fishes is a good one, because it shows us clearly the highly important fact that an organ originally constructed for one purpose, namely flotation, may be converted into one for a wholly different purpose, namely respiration.
[note: Darwin gets this one backwards, Maynard-Smith's version is the currently accepted one]
In considering transitions of organs, it is so important to bear in mind the probability of conversion from one function to another, that I will give one more instance. Pedunculated cirripedes have two minute folds of skin, called by me the ovigerous frena, which serve, through the means of a sticky secretion, to retain the eggs until they are hatched within the sack. These cirripedes have no branchiae, the whole surface of the body and sack, including the small frena, serving for respiration. The Balanidae or sessile cirripedes, on the other hand, have no ovigerous frena, the eggs lying loose at the bottom of the sack, in the well-enclosed shell; but they have large folded branchiae. Now I think no one will dispute that the ovigerous frena in the one family are strictly homologous with the branchiae of the other family; indeed, they graduate into each other. Therefore I do not doubt that little folds of skin, which originally served as ovigerous frena, but which, likewise, very slightly aided the act of respiration, have been gradually converted by natural selection into branchiae, simply through an increase in their size and the obliteration of their adhesive glands. If all pedunculated cirripedes had become extinct, and they have already suffered far more extinction than have sessile cirripedes, who would ever have imagined that the branchiae in this latter family had originally existed as organs for preventing the ova from being washed out of the sack?
Posted by: niiicholas on June 11 2002,05:07
Now, to show that cooption is not only well-known to the old and grey (or dead), but is very much a concept in modern use:
Consider this article:
< link >
Trends Genet 2001 Mar;17(3):120-3
Were protein internal repeats formed by "bricolage"?
Lavorgna G, Patthy L, Boncinelli E.
DIBIT, Istituto Scientifico H. S. Raffaele, Via Olgettina 60, 20132 Milan, Italy. firstname.lastname@example.org
Is evolution an engineer, or is it a tinkerer--a "bricoleur"--building up complex molecules in organisms by increasing and adapting the materials at hand? An analysis of completely sequenced genomes suggests the latter, showing that increasing repetition of modules within the proteins encoded by these genomes is correlated with increasing complexity of the organism.
The introduction reveals just how far the IDists are from the biologists on understanding the origins of new genetic information and new functions:
Evolution has brought about the formation of organisms of increasing complexity. This process involved mechanisms, such as exon-shuffling  and gene duplication,  that increased intermolecular duplications of the more sophisticated proteomes. For example, gene duplication contributed to the origin and evolution of vertebrates, which appear to possess several copies of an ancestral set of genes.  A single gene in flies usually has three or four paralogous genes in mammals, and this spare genetic capacity has permitted new possibilities, allowing the acquisition of new biochemical functions and expression capabilities. 
More than two decades ago, when only a handful of eukaryotic genes were cloned, Francois Jacob had already envisioned some of these basic evolutionary mechanisms.  In fact, he argued that evolution could work as a tinkerer, rather than an engineer, implying that evolutionary processes construct things with the materials at hand and the outcome bears the constraints imposed by those materials.  Translated into molecular terms, the raw materials are the existing set of genes, which can be, in part or entirely, elaborated again and redeployed to a new function during evolution. Extending to Jacob's view of `recyclement' of biological material, we investigated systematically the possibility that, besides the increase of inter-molecular duplications, an increase of intra-molecular duplications accompanied the evolution of proteins.
We decided to look for repeated protein modules, as opposed to short, low-complexity sequence repeats (i.e. runs of Qs, STSTSTSTS, etc) because, in several instances, modules of proteins are used to build the function of many multidomain proteins. As a result, we found, with a few exceptions, that:
1. There is a correlation between the complexity of functions controlled by the proteome of a given organism and its degree of internal repetitiveness.
2. The above correlation is often observed both for interdomain comparisons (e.g. archaeal proteins have, on average, more internal repeats than bacterial ones) and intradomain comparisons (e.g. human proteins have more internal repeats than those belonging to Drosophila melanogaster).
3. We also detected a decrease in the number of internal repeats following `reductive' evolution, in which the biological complexity of an organism is lower than that of its ancestor (occurring in, for example, endosymbiotic organisms).
A previous paper by Marcotte et al ., reported an analysis of 16 completely sequenced genomes (11 bacterial, four archaeal and one eukaryal), in which eukaryotic proteins displayed significantly more repeats than procaryotic ones. This study, which considered repeats containing both low-complexity and high-complexity sequences, was somewhat hindered by the availability of completely sequenced genomes ¯ then relatively scarce. In fact, some of the conclusions we reached are fairly subtle. For example, the increase of the protein repetitiveness from Bacteria to Archaea involves only small percentage changes, possibly because the trend was coupled with the massive gene exchange that occurred later in the microbial world.  A sufficiently high number of sequences needed to be analyzed to make our observations significant.
[& towards the end]
5. Mechanisms involved in intramolecular duplication
What mechanisms could have caused or favored the phenomenon of the increase of intramolecular duplications during evolution? There is a strong evidence for the involvement of intronic recombination and exon shuffling in the occurrence of gene insertions.  Intriguingly, we found the highest level of intramolecular duplications within high eukaryotic genomes, like C. elegans, D. melanogaster and Homo sapiens, whose genes are characterized by the presence of large numbers of exons and introns.  The invention of modular proteins could have been the mysterious force driving the acceleration of evolution and leading to a spectacular burst of evolutionary creativity ¯ the `Big Bang' of metazoan evolution ¯ that caused the sudden appearance of several phyla of animals with different body plans during the Cambrian period. 
Archaeal proteins, although belonging to intronless organisms, were found to possess, on average, a higher repetitiveness than the relatively less-evolved bacterial ones. Studies on the evolution of multidomain prokaryotic proteins have given insights on how they may be constructed without the assistance of introns. For example, a modular protein of Peptostreptococcus magnus is the product of a recent intergenic recombination of two different types of streptococcal surface protein.  Also, gene rearrangements can be facilitated by the presence of special recombinogenic DNA sequences in intermodule linker regions.  It has been proposed that an evolutionary bottleneck, such as the increased selective pressure given by the presence of antibiotics, could favor the creation of these advantageous chimeras.  A similar or identical environmental challenge could have been the stimulus directing the rapid evolution of new bacterial proteins and leading to the formation of the archaeal domain.
The data reported here, although suggestive, need to be extended. This will be possible when some more of the several genome sequencing projects currently underway are completed. However our results provide another indication that biological evolution works like a tinkerer, "who does not know exactly what he is going to produce, but uses whatever he finds around him whether it be pieces of string, fragments of wood, or old cardboards; in short, it works like a `bricoleur' who uses everything at his disposal to produce some kind of workable object". 
5. F. Jacob, Evolution and tinkering. Science 196 (1977), pp. 1161¯1166.
6. F. Jacob, Molecular tinkering in evolution. In: D. Bendall, Editor, Evolution from Molecules to Man, Cambridge University Press (1983), pp. 131¯144.
Posted by: niiicholas on June 11 2002,05:41
Following the tangent of the evolution of repeats *within* protein sequences:
Protein Repeats: Structures, Functions, and Evolution
pp. 117-131 (doi:10.1006/jsbi.2001.4392)
Miguel A. Andrade*, , Carolina Perez-Iratxeta*, , Chris P. Ponting
Internal repetition within proteins has been a successful strategem on multiple separate occasions throughout evolution. Such protein repeats possess regular secondary structures and form multirepeat assemblies in three dimensions of diverse sizes and functions. In general, however, internal repetition affords a protein enhanced evolutionary prospects due to an enlargement of its available binding surface area. Constraints on sequence conservation appear to be relatively lax, due to binding functions ensuing from multiple, rather than, single repeats. Considerable sequence divergence as well as the short lengths of sequence repeats mean that repeat detection can be a particularly arduous task. We also consider the conundrum of how multiple repeats, which show strong structural and functional interdependencies, ever evolved from a single repeat ancestor. In this review, we illustrate each of these points by referring to six prolific repeat types (repeats in -propellers and -trefoils and tetratricopeptide, ankyrin, armadillo/HEAT, and leucine-rich repeats) and in other less-prolific but nonetheless interesting repeats.
< http://www.idealibrary.com/servlet/citation/1047-8477/134/117 >
< pubmed >
[...see especially the ribbon models in this paper]
Our survey of protein repeats has highlighted the multifunctionality of repeat types, their structural
differences, and their proliferations in different evo-lutionary
lineages. One likely reason for their evo-lutionary success is that repeat-containing proteins are relatively “cheap” to evolve. By this we mean that large and thermodynamically stable proteins may arise by the simple expedient of intragenic du-plications, rather than the more complex processes of de novo a-helix and b-sheet creation. This is sup-ported by the larger sizes of most repeat-containing
structures relative to compact domains (Fig. 4).
This does not, of course, present a complete an-swer
to their success since it addresses the question of how repeat-containing proteins arose, rather than why they have been selected for and fixed in evolu-tionary lineages on so many separate occasions. As suggested throughout this review, the reasons for the functional successes of repeat classes may be a proclivity of repeat assemblies to acquire different molecular functions, namely, the association with
different protein ligands. This, in turn, might be associated with the large solvent-accessible surface areas, presented by extended “open” assemblies, that are available for interactions with ligands. This is because burial of nonpolar residues at protein–protein interfaces is thought to be an important contributor to heterodimer stability (Tsai et al.,
In understanding the evolution of repeats, one major problem remains. Repeats are defined as oc-curring multiply, and all repeats in a family are homologous. This means that these repeats all evolved from a common ancestor, which necessarily must have contained only a single repeat. This is
apparently contradictory, since it is not expected that a single repeat could exist in isolation, as a single folded functional unit. Rescue is at hand if one suggests that the family’s common ancestor indeed represented a single repeat, but one that formed homooligomers. The homooligomeric structure of the ancestor might mirror that of the intrachain repet-itive structure of its modern homologue, except in its multichain character. This scenario has recently been suggested for the evolution of the b-trefoil fold (Ponting and Russell, 2000).
A problem with this proposal is that there are few, if any, known examples where homologous multire-peat assemblies are formed both from oligomers of single repeats and from a single chain of multiple repeats. However, this might not be too surprising since the highly cooperative process of folding a mul-tirepeat protein must be significantly more favor-able
than folding a homooligomeric protein from its constituent monomers. This is because the kinetic folding pathways of multirepeat protein structures may be nucleated at many positions. In this way ancient oligomeric single repeat proteins might have been driven to extinction by their monomeric multi-ple repeat-containing homologues.
There is an interesting analogy here to the "serial homology" concept in traditional organismal evolution -- e.g. the duplication and specialization of segments. The same idea -- duplication and divergeence -- appears to occur on several different molecular levels, to wit:
- duplication of segments of a protein, followed by rapid divergence (the above paper)
- taking a homodimer, homotrimer, etc., duplicating the gene, and then specializing each gene in the e.g. heterodimer. This is yet another way to produce IC by the way
- traditional gene duplication
- duplication of whole chromosomes/genomes -- many chunks will decay but some may get new functions.
All this could be treated in much more detail. However, antievolutionists consistently fail to realize the importance of duplication, and write as if it didn't exist. E.g., John Bracht's recent post to metanexus:
Knotty Pine and Corroding Coins: John Bracht
< link >
For concreteness, consider an example. Think of a man-made outboard motor. This system contains many of the same structures found in the bacterial flagellum: a motor (including stator, rotor, and acid-powered drive), drive shaft, u-joint, and propeller. Now, imagine starting with a basic rowboat and trying to evolve an outboard motor via the co-optation model. Perhaps, somehow, the metal outer skin of the boat peels up in the back and this forms a useful rack for a fishing pole, and is available to provide the internal support and external protective casing for the motor. Perhaps a support rod works loose from the hull and is available to be made into a drive shaft. But how do we move on from here to build up the motor, in functional steps, from existing parts? The problem is this: the various parts are already adapted to their old functions. To build an outboard motor, the old functions must be replaced by new functions. New functions require modifications of the old parts, and since the motor system doesn't work until all the parts are assembled, we inevitably need a large amount of coordinated change in various components before we can build the new system. For instance, the peeled-away metal on the back (previously adapted to form a watertight hull) will have to undergo extensive modification, including careful bending or shaping, and drilling holes in appropriate places to support motor components (all without letting the hull become leaky). The support rod from the hull, destined to become the drive shaft, will also need modification for attaching gears and the universal joint (and the removal of the support rod must not weaken the structural integrity of the boat). And so on.
IMO there is a clear assumption here that we are dealing with *one* copy of everything, that the old function is lost as the new function is gained. But just ain't so...
Posted by: niiicholas on Feb. 17 2003,19:06
I'd forgotten that I'd accumulated these, they were posted originally in the ISCID immune system thread:
Dr. Dembski writes:
By your great mass of words and facts you've lost the train of the argument. The issue is not whether pieces exist for cooption (whether in the same organism or, with the immune system, even in different organisms) but whether those pieces can properly be coordinated to produce the final function in the IC system under examination. For cooption to work there has to be coordination. Design is known to have the capability to effect such coordination. You're claiming that natural selection does as well, but there is no evidence of that.
There are no two ways about it, this is false. I think that even Peonie and Mike Gene would agree with me on this one. There are dozens of examples of the origin of new genes and even multigene systems in either modern times or geologically recently enough that the direct evidence of natural selection remains in the genome, and *very* detailed pathways, on the level of individual nucleotide changes, have been traced in many instances.
A few of the examples are described < here >.
Here is a list, just off the top of my head. References can be found easily by searching PubMed so I trust you will not mind if for the purposes of space I just list some of the cases I know about without giving refs for all of them.
The recent-origin Drosophila genes jingwei and sdic
Nylon degradation genes (multiple independent origins)
Recent origin of antifreeze genes in fish (and plants)
Antibiotic and antipesticide genes
Here is a case of the origin of an autotransporter (AT) gene, lav by domain shuffling; I quote just a bit, the whole rather long article with all of their documenting evidence is < freely online at pubmed >:
A mosaic origin for lav was inferred from a G+C content transition at the boundary of its presumed passenger domain with the linker and -barrel domains. Similarly, the junction of nonhomology between lav and las coincides with the G+C transition and inferred domain boundaries of both genes. On the basis of quite different evidence (discordance between phylogenies based on individual domains), Loveless and Saier have proposed that AT proteins evolve by domain shuffling (28). A functionally novel AT can arise by linking a new passenger activity to a generic -barrel pore. Our analysis provides independent evidence for the combinatorial origin and subsequent reshuffling of at least one AT protein.
As biotype aegyptius strains and Int1 belong to different phylogenetic subgroups, it is unlikely that they inherited lav from a common ancestor. Rather, it is likely that the first H. influenzae clade to acquire the gene passed it to one or more other clades by transformation and homologous recombination within flanking DNA. Once a laterally transferred fragment has been acquired by a population of naturally transformable bacteria, it can readily be assimilated into the species by co-opting linked homologous sequence and uptake signals. Interstrain and interspecies transfer implies a shared selective advantage in certain host environments.
For the evolution of multigene systems, even those with multiple-parts -required, see:
Mortlock, R. P., editor (1992). The Evolution of Metabolic Function Boca Raton Fla., CRC Press, pp. 1-339.
Table of contents:
1) Experiments in the Evolution of Catabolic Pathways Using Modern Bacteria
2) Natural and Experimentally Evolved Pathways for the Utilization of D-Arabinose in Enteric Bacteria
3) The Development of a Catabolic Pathway for Ethylene Glycol
4) Evolution of [alpha]-Aminoadipate Pathway for the Synthesis of Lysine in Fungi
5) Common Ancestry of Escherichia coli Pyruvate Oxidase and the Acetohydroxy Acid Synthase of the Branched-Chain Amino Acid Biosynthetic Pathway
6) Evolution of Bacterial Alcohol Metabolism
7) Microbial Metabolism of Mandelate: Occurence, Function, Properties, and Evolution of Mandelate Dehydrogenases and Other Enzymes of the Mandelate Pathway
8) Evolution of the Bacterial Phosphoenolpyruvate: Sugar Phosphotransferase System
Section I: Physiologic and Organismic Considerations
Section II: Molecular Considerations
9) An Emerging Outline of the Evolutionary History of Aromatic Amino Acid Biosynthesis
10) Life Before DNA: The Origin and Evolution of Early Archean Cells
11) The Prebiotic Evolution of Complex Molecules: A Central Role for Catalyzed Cells
...and lots of articles published since 1992, e.g.:
On atrazine resistance (lots of articles < here >)
The degradation of pentachlorophenol by the recent assembly of a multiple-parts-required pathway, e.g.:
Copley SD. < Evolution of a metabolic pathway for degradation of a toxic xenobiotic: the patchwork approach >. Trends Biochem Sci. 2000 Jun;25(6):261-5.
Anandarajah K, Kiefer PM Jr, Donohoe BS, Copley SD. < Recruitment of a double bond isomerase to serve as a reductive dehalogenase during biodegradation of pentachlorophenol >. Biochemistry. 2000 May 9;39(18):5303-11.
An even more sophisticated example is Johnson et al.'s (2002) article, "< Origins of the 2,4-Dinitrotoluene Pathway >". 2,4-dinitrotoluene (DNT) is another recently human-introduced compound, and yet bacteria have assembled a quite complex pathway for its degradation. The summary of the reconstructed evolution of the pathway is also quite complex (and detailed):
Inferences from the comparison of the structural genes of the 2,4-DNT pathway suggest that the pathway came together from three sources. The initial dioxygenase appears to have originated from a naphthalene degradation pathway like that of strain U2 (17). A large portion of the salicylate hydroxylase oxygenase component is retained but is not functional. The MNC monooxygenase was probably derived from a pathway for degradation of chloroaromatic compounds. The presence of the vestigial (with respect to 2,4-DNT degradation) ortho-ring fission dioxygenase is consistent with its recruitment from a pathway for chloroaromatic compounds. The true ring fission enzyme for 2,4-DNT degradation has a different origin. The sequence of DntD is quite dissimilar to all other described meta-ring fission enzymes, including those from naphthalene and chloroarene degradative pathways. The distinctive sequence of the ring cleavage enzyme reflects the substrate specificity observed for the THT oxygenase (28). The distant relationship between homogentisate dioxygenase and DntD and the association with homologs from amino acid metabolism (dntE and dntG) indicate that the lower pathway operon arose from a gene cluster for amino acid degradation.
The disparate origins of the various dnt and associated genes described in this study are consistent with the difficulties that bacteria face to achieve efficient metabolism of synthetic compounds like 2,4-DNT. The organization of the pathway genes suggests there is a progression towards a compact region en-coding the entire pathway. In that progression, remnants from assembly persist, such as the benzenetriol oxygenase (ORF3), putative maleylacetate reductase (ORF10), and putative trans-posase (ORF4). No role in nitroarene degradation is apparent for the remnants; their presence might indicate an intermediate point in the evolution of an optimal system or perhaps some of the proteins could be used in other pathways when another substrate is available.
And numerous review articles that review the topic of cooption:
Otto SP, Yong P. < The evolution of gene duplicates >. Adv Genet 2002;46:451-83 Related Articles, Links
Betran E, Long M. < Expansion of genome coding regions by acquisition of new genes >. Genetica. 2002 May;115(1):65-80.
Kondrashov FA, Rogozin IB, Wolf YI, Koonin EV. < Selection in the evolution of gene duplications >. Genome Biol 2002;3(2):RESEARCH0008 (free online)
Eizinger A, Jungblut B, Sommer RJ. < Evolutionary change in the functional specificity of genes >. Trends Genet 1999 May;15(5):197-202
Hughes A. < Adaptive evolution after gene duplication >. Trends Genet 2002 Sep;18(9):433
Ganfornina MD, Sanchez D. < Generation of evolutionary novelty by functional shift >. Bioessays. 1999 May;21(5):432-9.
Long M. < Evolution of novel genes >. Curr Opin Genet Dev 2001 Dec;11(6):673-80
True JR, Carroll SB. < Gene Co-Option in Physiological and Morphological Evolution >. Annu Rev Cell Dev Biol. 2002
Here's a case of cooption in a slightly different sense, but returning to one of my original points: microbes "designed" to subvert the immune system:
Immunology 2001 Jan;102(1):2-7
< Co-option of endocytic functions of cellular caveolae by pathogens. >
Shin JS, Abraham SN.
It is increasingly becoming clear that various immune cells are infected by the very pathogens that they are supposed to attack. Although many mechanisms for microbial entry exist, it appears that a common route of entry shared by certain bacteria, viruses and parasites involves cellular lipid-rich microdomains sometimes called caveolae. These cellular entities, which are characterized by their preferential accumulation of glycosylphosphatidylinositol (GPI)-anchored molecules, cholesterol and various glycolipids, and a distinct protein (caveolin), are present in many effector cells of the immune system including neutrophils, macrophages, mast cells and dendritic cells. These structures have an innate capacity to endocytoze various ligands and traffic them to different intracellular sites and sometimes, back to the extracellular cell surface. Because caveolae do not typically fuse with lysosomes, the ligands borne by caveolar vesicles are essentially intact, which is in marked contrast to ligands endocytozed via the classical endosome-lysosome pathway. A number of microbes or their exotoxins co-opt the unique features of caveolae to enter and traffic, without any apparent loss of viability and function, to different sites within immune and other host cells. In spite of their wide disparity in size and other structural attributes, we predict that a common feature among caveolae-utilizing pathogens and toxins is that their cognate receptor(s) are localized within plasmalemmal caveolae of the host cell.
In other words, like the evidence for the evolution of the immune system, the evidence for cooption by natural processes has gobbs of evidence and literature behind it. Yet Dembski asserts that there is "no evidence" for it.
The only evidence is of isolated pieces waiting to be coordinated. That's why I insist on **detailed** Darwinian pathways (and no, you haven't provided them). Pathways are continuous trajectories that connect the dots. The issue is not whether the dots are in place but how to connect them.
The previous claim of the IC argument was that the dots couldn't exist because they wouldn't be functional. Now you're conceding that they exist, but quibbling over how "detailed" the reconstructed pathways are, and yet you still refuse to explicitly say what counts as "detailed" for you or to justify that level of detail as an appropriate standard of judgement of evolutionary explanations. The goalposts are on wheels. The standard in science is clear however: testability and passed tests, and this is the one I advocate, and which I think all evolutionary immunologists would argue is being successfully applied in the field. Compared to "IDdidit" (where's your details there, Dr. Dembski?) the reconstructed origin of the immune system is quite detailed, and getting more so all of the time.
You've offered no evidence that natural selection can do that -- or is your evidence simply that it couldn't have been design and therefore natural selection is all that's left? That sounds like an argument from ignorance.
Nope, the known natural processes of mutation and selection make predictions about what should be seen in the data, which I outlined in a previous post, and in this thread I'm arguing that the evidence and the literature on the origin of the IC immune system supports those predictions. Some have made suggestions in the thread that, basically, maybe ID did it even though it looks like natural processes (employing small changes, cooption etc. predicted by RM&NS) were responsible; this cannot of course be ruled out, but my point is that ID does not *predict* these observations while RM&NS does.
Posted by: niiicholas on Mar. 29 2003,17:43
A recent post of mine that I rather like:
(follows some discussion of eye evolution)
< Topic: Distinguishing Mechanisms of Co-option, started by John Bracht >
This is the question I am trying to get at in this thread: how do we know that Darwinian co-option events really occurred by a non-intelligent mechanism? My experience is that there is no "test" that Darwinian thinkers apply to co-option events; rather they simply look at protein similarities and use that as "evidence" for their view. My point is that a design-driven co-option event would look exactly the same from our vantage point and hence the Darwinian comparison-of-similarity approach doesn't really test different mechanisms that might have been responsible for a given system.
This is the problem with the "vague designer" hypothesis -- an uncharacterized designer could, for all we know, do things however the heck he wants. The "vague designer" hypothesis can "explain" not only observations supporting standard evolutionary biology but also any other set of observations.
Darwin had a similar problem: once he had convinced someone that the special creation "poof" model was untenable, a common response was to retreat to a vaguer position such as "the plan of Creation" or whatnot. There are some great Darwin quotes somewhere on just how scientifically useless such statements are, unfortunately I can only find one at the moment:
It is so easy to hide our ignorance under such expressions as the “plan of creation,” “unity of design,” &c., and to think that we give an explanation when we only restate a fact. (< OoS >)
To get a little more specific, consider one major difference between human intelligent design and "design" as seen in biology. Human designs -- such as transistors, computers, radios, plastics, GPS systems, etc., etc., -- get invented in one place and then transplanted wholesale into a multiude of other "lineages" -- cars, boats, planes, rockets, etc. In biology, on the other hand, the transmittance of designs through lineages appears to be strictly limited to that allowed by known processes of heredity, namely:
1) Lineal descent (parents to children, species to descendent species). This is the major one.
2) or, sometimes, lateral gene transfer (although this seems to be limited to fairly simple systems that can fit on plasmids and subject to a number of other constraints, e.g. rare in things like metazoans with protected germline cells).
In other words, in human design you see an invention originate and then get basically simultaneously integrated across a wide range of "lineages". In biological design the invention sits in whatever lineage it originated in (small groups of genes on mobile genetic elements being the exception, with a known and observed natural mechanism).
The fact that putative instances of cooption (the "same" structure being used for different functions) appear to follow the above pattern to a tee seems to me to be a perfect example of John's request regarding:
how do we know that Darwinian co-option events really occurred by a non-intelligent mechanism?
There is no reason for us to expect a designer to constrain design-transmittance to the processes of heredity; and yet we see such constraints, as we would expect based on common descent (= the continous operation of everday heredity).
However, a typical response that I've seen is to invoke front-loading, or "maybe the designer constrained himself to work within lineages for some reason", or "the designer might work in mysterious ways", or some other backup defense in order to save design from the falsification given in the above argument. And this gets us back to Darwin's point about how vague designer-talk is scientifically vacuous and actually does no explaining at all.
In summary, you need at least a somewhat specific model of the designer (this does *not* require foreknowledge, just like any proposed hypothesis does not require foreknowledge) in order to have something with scientific tractability. If ID stays in the "vague" category -- then it will never rise above the level of other such vague ideas ("an immaterial innate force causes design").
PS: Another similar test is that:
1) Evolved cooptions will always have the "purpose" of increasing the reproduction of the genes of the organism carrying the new adaptation, but
2) There is no reason to expect such from IDed cooptions, indeed in human designs the designs are always meant to serve the purposes of the designer.
This is also, IMO, a good test, but again the IDist can escape by post-hoc appeals to a designer that mimics evolution for some reason. In doing so they escape the frying pan of falsification but fall into the fire of scientific vacuousness.
Posted by: niiicholas on July 05 2003,17:33
More fun with atrazine and related compounds:
< http://pubs.acs.org/cgi-bin....3r.html >
Biochemistry, 40 (43), 12747 -12753, 2001. 10.1021/bi011293r S0006-2960(01)01293-4
Web Release Date: October 3, 2001
Copyright © 2001 American Chemical Society
Rapid Evolution of Bacterial Catabolic Enzymes: A Case Study with Atrazine Chlorohydrolase
Jennifer L. Seffernick and Lawrence P. Wackett*
This review discusses examples in which it is possible to sift through the complexity of the biosphere to find related enzymes which display distinct functions. The clearest example to date is atrazine chlorohydrolase, an enzyme which is shown to have evolved for the function of catabolizing atrazine. More than 2 billion pounds of the herbicide atrazine have been applied to soils globally, and this has provided selective pressure for the evolution of new metabolism. The amino acid sequence of atrazine chlorohydrolase is shown to be 98% identical with that of melamine deaminase, an enzyme that catalyzes deamination reactions. The chlorohydrolase is shown to be firmly linked with a major amidohydrolase protein superfamily.
Atrazine Catabolism and the Amidohydrolase Superfamily
The chlorinated herbicide atrazine was once considered to be poorly biodegraded in soils. The major metabolites detected in soils and groundwaters suggested that the herbicide underwent nonspecific oxidative dealkylation reactions (Figure 1). A cytochrome P450 monooxygenase from Rhodococcus strains TE1, N186/221, and B30 was subsequently discovered to catalyze this reaction (20-24). The bacterial cytochrome P450 was shown to degrade other herbicides structurally unrelated to atrazine and is likely functioning as a nonspecific oxygenative catalyst rather than an enzyme that has evolved specifically to catabolize atrazine. Starting in 1993, however, numerous bacteria were ascertained to initiate atrazine metabolism via a hydrolytic dechlorination reaction (Figure 2). More recently, the genes encoding the chlorohydrolase have been shown to be essentially identical in different genera of bacteria independently isolated from four continents by different researchers (25). This suggests that the ability to dechlorinate atrazine arose since the introduction of atrazine and that this phenotype spread quickly around the globe.
The enzymes responsible for the first three steps of the atrazine dehalogenation pathway were initially identified in Pseudomonas sp. strain ADP (Figure 2). The enzymes that catalyze these steps are atrazine chlorohydrolase (AtzA, EC 22.214.171.124), hydroxyatrazine ethylaminohydrolase (AtzB, EC 126.96.36.199), and N-isopropylammelide N-isopropylaminohydrolase (AtzC, EC 188.8.131.52), respectively. Sequence comparisons revealed that all three enzymes belong to the amidohydrolase superfamily (26). Amidohydrolase superfamily members for which structures are defined have an ()8 barrel structure (27, 28). Moreover, they share conserved features of the reaction mechanism in which one or two divalent metals are coordinated by the enzyme and serve to activate water for nucleophilic attack on the respective substrate. The amino acids serving as metal ligands are maintained across the superfamily. The majority of reactions catalyzed by the superfamily involve the hydrolytic removal of amino groups from purine and pyrimidine rings, or amide bond hydrolysis reactions (Figure 3). The former reactions are represented by enzymes such as adenosine deaminase. The latter are illustrated by urease and cyclic amidases such as hydantoinase.
Recent studies have expanded the range of reactions that are known to be catalyzed by amidohydrolase superfamily members (Figure 3). Some of the existing enzymes catabolize synthetic organic compounds (Table 1). Phosphotriesterase, for instance, catalyzes the cleavage of a phosphorus-oxygen bond of the pesticide parathion (29). It has been speculated that the true substrate for phosphotriesterase from Pseudomonas dismuta is yet to be discovered. But it is also plausible that the enzyme has evolved under selective pressure to hydrolyze phosphotriester insecticides since their introduction some decades ago.
Other data support the view that the Pseudomonas AtzA evolved under selective pressure and was maintained in soil microbial populations to metabolize s-triazine herbicides. The atzA gene was not found in randomly chosen laboratory strains but was detected in most bacteria recently isolated for their ability to metabolize atrazine (25). It is present with other genes, atzB and atzC, which encode enzymes that metabolize the AtzA reaction product in Pseudomonas sp. ADP Ralstonia, Alcaligenes, and Agrobacterium strains (Figure 2) (25). The atrazine catabolism genes are found on large catabolic plasmids in those same strains (42).
Melamine Deaminase and s-Triazine Hydrolase
Perhaps the best evidence that atzA is a recently evolved gene derives from its relationship with genes identified for the catabolism of melamine, or 2,4,6-triamino-1,3,5-triaizine. Melamine is an industrial product used since the early 1900s. Melamine was considered nonbiodegradable in the 1930s but was then reclassified as slightly biodegradable in the 1960s when atrazine was first introduced (43). Today, it is considered to be readily biodegradable in soil. Among the bacteria that metabolize melamine is Acidovorax avenae citrulli 12227 (formerly Pseudomonas sp. strain NRRL B-12227) (44). The first two metabolic reactions are sequential hydrolytic deamination reactions catalyzed by the same enzyme, melamine deaminase (TriA). The triA gene has recently been cloned and sequenced. The protein shows a remarkable identity to atrazine chlorohydrolase from Pseudomonas sp. ADP; it is the same in 466 of 475 amino acids (Figure 4) (45). It is also unusual that the nine nucleotide differences between triA and atzA give rise to these nine amino acid changes. The small number of changes and the absence of silent mutations are consistent with an intense selective pressure operating over a short evolutionary time period (46, 47). The kcat/Km of atrazine chlorohydrolase with atrazine is 1.5 × 104 s-1 M-1 per subunit. In our most recent study, the deamination activity of this enzyme was found to be undetectable (48). Melamine deaminase, however, exhibits the opposite specificity. It catalyzes deamination reactions at rates comparable to dechlorination rates of atrazine chlorohydrolase. Moreover, it shows dechorination activity 2 orders of magnitude lower than the deamination activity with comparable triazine substrates. In total, these data suggest that the nine amino acid changes represent a short evolutionary trajectory between the two activities.
The sequence of a related amidohydrolase superfamily member, s-triazine hydrolase or TrzA (49), is 41 and 42% identical with the sequences of atrazine chlorohydrolase and melamine deaminase, respectively. It catalyzes both deamination and dechlorination reactions. TrzA catalyzes the deamination of nonalkylated triazines such as melamine and the dechlorination of mono-N-alkylated triazines. The kcat for deamination of melamine is 243 s-1, while that for the dechlorination of desisopropylatrazine is 2.2 s-1. This is an approximately 100 times greater preference for demination over dechlorination and is consistent with the enzyme acting physiologically as a deaminase with a fortuitous dechlorination activity. This is not surprising given that chloride displacement is more facile, and adenosine deaminase is known to catalyze fortuitous halopurine dehalogenation. That TriA and AtzA discriminate between chloro and amino substrates so well despite their sequences being 98% identical is remarkable.
It is possible that fewer than nine amino acid changes are required to interconvert melamine deaminase and atrazine chlorohydrolase activities. There are 510 possible site-directed mutants bridging the two, a large set to generate, sequence, purify, and assay. In this context, DNA shuffling was conducted and the clonal variants were screened against a chemical library of substrates using high-throughput mass spectrometry (48). The chemical library of 15 substrates varied the leaving group and the side chains (Figure 5). Mutant enzymes were obtained that varied with respect to their activities against the different substrates. The sequences of daughter enzymes exhibiting the greatest activity for hydrolysis of atrazine analogues are displayed in Table 2. The activities of the shuffled clones were normalized to the activity of each parental enzyme. The clone with the best dechlorination activity was 1.4 times as fast as atrazine chlorohydrolase, and the clone with the best deamination activity was 3.6 times better than melamine deaminase. The small increases observed in activity upon shuffling suggest that atrazine chlorohydrolase and melamine deaminase have among the most optimal sequences for dechlorination and deamination activities, respectively.
It is also of potential evolutionary significance that shuffled mutants were obtained with 80-fold enhanced activities with substrates containing methyl thioether and methoxy substituents. These represent the commercially relevant herbicides ametryn and atraton, respectively. An enzyme purified from a Nocardioides sp. was shown to hydrolyze ametryn, but it was not tested with atraton or other methoxy-functionalized herbicides (50). DNA from the Nocardioides sp. did not hybridize to an atzA probe, suggesting that the enzyme does not closely resemble atrazine chlorohydrolase from Pseudomonas sp. ADP. However, the data in Table 2 suggest that enzymes capable of metabolizing ametryn, atraton, and related triazine herbicides could be derived from triA or closely homologous genes in nature.
With respect to the sequences that favor dechlorination versus deamination, the data show a trend in that residue 328 appears to largely control leaving group specificity. Asn328 tracks with narrow specificity enzymes that largely catalyze dechlorination. Asp328 tracks with broader specificity enzymes which catalyze deamination and the displacement of -NCH3, -OCH3, and -SCH3 groups. The hypothesis that this residue is crucial to the observed specificity difference between melamine deaminase and atrazine chlorohydrolase is currently being addressed with site-directed mutagenesis studies.
Nature must continually fine-tune enzyme substrate specificities and reaction rates over time under the aegis of biological need, usually called selective evolutionary pressure. This enzyme variability is particularly marked with soil bacteria due to their enormous numbers, large evolutionary span of 3.6 billion years, rapid reproductive rates, and great competition for scarce nutrient resources. Enzyme plasticity is important in this context, but this confounds genome annotation efforts where gene function is assigned on the basis of finding the homologue with the most identical sequence. As discussed here, enzymes with sequences that are 98% identical can catalyze different reactions. It will be imperative to flesh out a broader range of microbial enzymatic reactions, particularly for microbial catabolic enzymes where the diversity of enzymes will likely be great.