Joined: May 2002
repost from my new ISCID thread:
New article on the evolution of blood-clotting
Doolittle and an associate have just published a new article on the evolution of the blood-clotting cascade in PNAS:
Proc Natl Acad Sci U S A. 2003 Jun 13 [Epub ahead of print].
The evolution of vertebrate blood coagulation as viewed from a comparison of puffer fish and sea squirt genomes.
Jiang Y, Doolittle RF.
Center for Molecular Genetics, University of California at San Diego, La Jolla, CA 92093-0634.
The blood coagulation scheme for the puffer fish, Fugu rubripes, has been reconstructed on the basis of orthologs of genes for mammalian blood clotting factors being present in its genome. As expected, clotting follows the same fundamental pattern as has been observed in other vertebrates, even though genes for some clotting factors found in mammals are absent and some others are present in more than one gene copy. All told, 26 different proteins involved in clotting or fibrinolysis were searched against the puffer fish genome. Of these, orthologs were found for 21. Genes for the "contact system" factors (factor XI, factor XII, and prekallikrein) could not be identified. On the other hand, two genes were found for factor IX and four for factor VII. It was evident that not all four factor VII genes are functional, essential active-site residues having been replaced in two of them. A search of the genome of a urochordate, the sea squirt, Ciona intestinalis, did not turn up any genuine orthologs for these 26 factors, although paralogs and/or constituent domains were evident for virtually all of them.
Here is figure 5 (and discussion) from Jiang & Doolittle's article:
|Assembling the Scheme. |
It is thought that 50–100 million years separate the appearances of urochordates (which include the sea squirt) and vertebrates. During that time the machinery for thrombin-catalyzed fibrin formation had to be concocted by gene duplication and the shuffling about of key modular domains. The relative times of duplicative events can be estimated by various means, the most obvious being the presence or absence of a gene in earlier diverging organisms, although it must be kept in mind that lineages may lose genes. Another way to gauge events is from the relative positions of various gene products on phylogenetic trees, earlier branching implying earlier appearance. In this regard, (pro)thrombin invariably appears lower on the phylogenetic trees than do the other vitamin K-dependent factors (Fig. 2).
The order of events can also be inferred by considering the most parsimonious route to assembling the various clusters of peripheral domains. Nine of the proteases under discussion can be accounted for by six domain-swapping events (Fig. 5). Indeed, the presence of a multiple-kringle protease in the sea squirt genome provides a reasonable model for a step-by-step parallel evolution of the clotting and lysis systems. It should be noted that a serine protease with only one kringle has been found in the ascidian Herdmania momus (36). Although numerous scenarios have been offered in the past about how modular exchange was involved in generating these schemes (refs. 4, 12, and 37–41, inter alia), the new genomic data now provide a realistic set of starting materials.
The timing of duplicative events can also be approximated from ortholog–paralog comparisons. As an example, human and puffer fish factor V are 41% identical, and human and puffer fish factor VIII are 42% identical (not counting the variable B regions). On the average, the two factors themselves (in this region) are 38% identical, implying that the gene duplication that led to them occurred only a relatively short while before the common ancestor of fish and mammals. The difference is so small (42% vs. 38%) that it may turn out that the earlier diverging jawless fish will have only the preduplication gene. A genome study devoted to the lamprey or hagfish would settle the point.
What I find interesting is how this work is presaged on 20 years+ of literature on the evolution of blood-clotting. For example, here are the references that Doolittle lists as some of the preceding work:
4. Doolittle, R. F. & Feng, D. F. (1987) Cold Spring Harbor Symp. Quant. Biol. 52, 869–874.
12. Doolittle, R. F., Feng, D. F. & Johnson, M. S. (1984) Nature 307, 558–560.
37. Patthy, L. (1985) Cell 41, 657–663.
38. Doolittle, R. F. (1985) Trends Biochem. Sci. 10, 233–237.
39. Patthy, L. (1990) Semin. Thromb. Hemostasis 16, 245–254.
40. Krem, M. W. & Di Cera, E. (2002) Trends Biochem. Sci. 27, 67–74.
41. Gherardi, E., Manzano, R. G., Cottage, A., Hawker, K. & Aparicio, S. (1997) in Plasminogen Related Growth Factors, eds. Bock, G. R. & Goode, J. A. (Wiley, New York), pp. 24–41.
Many more articles on the topic (the inter alia, as it were) have been accumulated here:
AE reference thread on the evolution of the blood-coagulation cascade
...and finally, several other recent articles advancing the discussion in the light of recently published genomes have also been published, e.g.:
Thromb Haemost. 2003 Mar;89(3):420-8.
Molecular evolution of the vertebrate blood coagulation network.
Davidson CJ, Hirt RP, Lal K, Snell P, Elgar G, Tuddenham EG, McVey JH.
Haemostasis Group, MRC Clinical Sciences Centre, The Faculty of Medicine, Imperial College, Du Cane Road, London W12 0NN, UK.
In mammalian blood coagulation 5 proteases, factor VII (FVII), factor IX (FIX), factor X (FX), protein C (PC) and prothrombin act with two cofactors factor V and factor VIII to control the generation of fibrin. Biochemical evidence and molecular cloning data have previously indicated that blood coagulation involving tissue factor, prothrombin and fibrinogen is present in all vertebrates. Using degenerate RT-PCR we have isolated and characterized novel cDNAs with sequence identity to the blood coagulation serine proteases and cofactors from chicken and the puffer fish (Fugu rubripes). Sequence alignments, phylogenetic and comparative sequence analysis all support the existence of the Gla-EGF1-EGF2-SP domain serine proteases FVII, FIX, FX, PC and the A1-A2-B-A3-C1-C2 domain protein cofactors FV and FVIII in these species. These results strongly suggest that the blood coagulation network is present in all jawed vertebrates and evolved before the divergence of tetrapods and teleosts over 430 million years ago; and that vertebrate blood coagulation may have benefited from two rounds of gene or whole genome duplication. Sequences identified in Fugu coding for additional FVII-like, FIX-like and PC-like sequences support the possibility of further tandem and large-scale duplications in teleosts. Comparative sequence analyses of amino acid residues in the active site region suggest these additional sequences have evolved new and as yet unknown functions.
Blood Cells Mol Dis. 2002 Jul-Aug;29(1):57-68.
Comprehensive Analysis of Blood Coagulation Pathways in Teleostei: Evolution of Coagulation Factor Genes and Identification of Zebrafish Factor VIIi.
Hanumanthaiah R, Day K, Jagadeeswaran P.
It is not clear how the complex mammalian coagulation pathways evolved from an entirely dissimilar invertebrate coagulation cascade. Comprehensive analysis of pro-coagulant factors and their regulators is lacking in early vertebrates to discern the mechanism of evolution of these genes from the invertebrates. To elucidate the coagulation pathways found in early vertebrates, zebrafish cDNAs/gene orthologues for major coagulant, anticoagulant, and fibrinolytic proteins were identified and characterized by homology to mammalian sequences. We found that zebrafish carry all hemostatic genes present in mammals, providing evidence that the coagulation system of teleosts is nearly identical to mammals. Zebrafish factor VII and X genes were identified and analyzed to reveal a novel factor VII-like gene flanked by the factor VII and factor X genes. This gene encodes a protein homologous to factor VII, but lacks critical residues for factor VII activity. Expression of the factor VII-like protein (named factor VIIi) demonstrated that it functions as an inhibitor of blood coagulation in biochemical assays using zebrafish or human plasmas. Analysis of intergenic DNA between the zebrafish VII/VIIi/X gene cluster and a Drosophila trypsin gene cluster revealed significant homology, and based upon these data, we propose a model for a rapid evolution of coagulation factors from the invertebrates.
So, when is Dembski going to retract the following?
STILL SPINNING JUST FINE: A RESPONSE TO KEN MILLER
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). Darwin's theory, without which nothing in biology is supposed to make sense, in fact offers no insight into how the flagellum arose. If the biological community had even an inkling of how such systems arose by naturalistic mechanisms, Miller would not -- a full six years after the publication of Darwin's Black Box by Michael Behe -- be lamely gesturing at the type three secretory system as a possible evolutionary precursor to the flagellum. It would suffice simply to provide a detailed explanation of how a system like the bacterial flagellum arose by Darwinian means. (italics original)
This is what really gets the goat of scientists -- pronouncements of the failure of entire disciplines by IDists like Dembski, when it's clear that Dembski hasn't done the slightest bit of actual reading, let alone consideration, let alone informed critical discussion in peer-reviewed journals, or the relevant literature. Sure, the origin of the flagellum is not yet well-understood (although there are number of plausible ideas and hints), but the IC argument was about a **class** of systems, called "IC systems", and when the literature on the evolution of *other* IC systems, like the immune system and blood-clotting system, is demonstrated, what is Dembski's response? Did it "suffice" to show him the literature? No, he just goes into denial mode.
Perhaps he will discuss it in his forthcoming book, but somehow I doubt it. Let's get real, Dr. Dembski.