7 August 2007

Würde mich mal interessieren, was Behe dazu zu sagen hätte.

Schon gelangweilt von Leuten, die Behes 'Edge of Evolution' auseinandernehmen? Trotzdem würde ich denen - und noch viel mehr jenen, die Behe ernst nehmen - dieses Post von ERV nahelegen. Da ich Behes Buch nicht gelesen habe und es auch höchst unwahrscheinlich ist, dass ich es je lesen werde, kann ich nur annehmen, dass sein Argument ungefähr so geht: "HIV mutiert unglaublich schnell und trotzdem hat es keine neuen Gene und/oder neue Funktionen evolviert. Also ist es unmöglich, dass das Leben auf der Erde sich ohne Eingreifen eines intelligenten Designers entwickelt hat."

ERV nimmt sich der Behauptung an, HIV hätte nichts Neues "entwickelt". Ich kann nur sagen: Autsch. Das ist nicht nur knapp daneben, das ist in etwa so weit entfernt von den tatsächlichen Verhältnissen wie zu behaupten, bei der Tour de France gewinne der mit dem größten Sportsgeist.

Vpu is, in fact, a new gene.1 Of the five major phylogenetic groups of SIV, Vpu is only found in one group– Chimpanzee SIV (SIVcpz) and its descendants – including HIV-1. It is absent in all of the other major lineages (Sooty Mangabey, African Green Monkey, Sykes Monkey, and L’Hoest Monkey). This means that Vpu is in HIV-1 but not HIV-2. [...]

SIVcpz Vpu and HIV-1 Vpu act in different ways, biochemically, which is predictable enough when you do something as simple as comparing amino acid sequences. For instance, if you compare a laboratory strain gag to SIVcpz gag, you get a similarity of ~75%.3 Not too shabby. On the other hand, if you compare the subunit portion of env (the gene I use to create phylogenetic trees because it’s the most variable between viruses) you get an AA similarity of only ~59.5%.

The amino acid similarity between HIV-1 Subtype B Vpu and SIVcpz Vpu is ~37%. Ah but that study was published in 1990. Perhaps things are different now? I found the AA sequence of NL4-3 (lab standard Subtype B) and several recently entered SIV cpz sequences at the Los Alamos National Laboratory HIV Sequence Database4 – I got the same numbers. Highest was ~39% AA sequence similarity. [...]

To put this the simplest way possible, Vpu involves the evolution of at least two protein-protein interaction sites – one to interact with CD4, one to interact with the pathway that degrades the CD4. [...]

But the ‘pathetic’ evolution doesn’t stop there. The feature both Vpus have in common, CD4 degradation, is carried out in completely different ways. HIV-1 Vpu requires two casein kinase II sites. You could almost call it irreducibly complex – if you dont have both CKII sites, CD4 isn’t degraded. Yet some SIVcpz Vpus have only one CKII site, and instead utilize a simple string of negatively charged amino acids in place of the second site. Different ways of performing similar tricks with totally different amino acids. I think that’s biochemically significant as well. [...]

Alas, ‘same number of genes that work in the same way’ goes beyond the differences between HIV-1 Vpu and SIVcpz Vpu. HIV-1 is divided into three groups, M, N, O. Group M is the one making a mess of the world right now, and is further divided into Subtype A, B, C, etc, and circulating recombinant forms of the subtypes (Subtype AG, for instance). Two relatively well characterized subtypes are Subtype B and C. Subtype C HIV can be defined by its Vpu, as it is so different from the other subtypes.

For instance, Subtype C Vpus are characteristically longer than the others, have key phosphorylation sites shifted, have an extra CKII site, and its tertiary structure is totally different (Subtype B Vpus have an Mr of 43,000 in an SDS-PAGE gel, while Subtype C is 34,000). But what does this mean, biochemically?

It turns out that one of the biochemical differences is that Subtype B Vps have a Golgi retention signal in the second alpha-helix of the cytoplasmic domain.13 This means that Subtypes B Vpu prefers (if you will excuse me personifying a virus) to be in the Golgi, helping degrade CD4, while Subtype C Vpu prefers to be in the plasma membrane, assisting with the release of new viruses. Michael Behe, if you don’t understand the epidemiological and clinical significance of this ‘pathetic’ evolution, well, that might explain why you aren’t doing HIV research.


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