REPOST: ERVs dubutante post

This is a repost from the old ERV. A retrotransposed ERV :P I dont trust them staying up at Blogger, and the SEED overlords are letting me have 4 reposts a week, so Im gonna take advantage of that!

I am going to try to add more comments to these posts for the old readers-- Think of these as 'directors cut' posts ;)

Last summer, when Behe released his tome-of-TARD 'Edge of Evolution', I had absolutely no intention of reading it. If Dude had anything to say, he would publish it. But I kept hearing from friends that he was saying some crazy stuff about HIV.

He was.

I corrected him.

There is nothing I would change about this post, at all. I luvs it.

Fun fact about this post, too, is that it set off a chain reaction of events that ultimately lead to many more laughs at the DIs expense:

  1. I write 'Hello Michael Behe'. Behe tries to ignore me.
  2. Uncommon Descent didnt get the memo. Invite me to UD to discuss HIV evolution, they act like 12 year old drunk boys, ban me after a handful of posts.
  3. Dembski comes to OU. I confront him about my treatment on his blog. Notice he stole something.
  4. Theft appears to be a personality defect of Mr. Dembski and his comrades, for it is noticed again and again and again and again once word spreads.

So essentially, all of this happened because Behe thought he would be a big baller and talk about HIV, when he knows nothing of its history, genetics, biochemistry, or overall evolutionary abilities.

May this post serve as a head-on-a-pike for current and future Creationists.

Michael Behe, please allow me to introduce myself...

Im ERV. This is my dog, Arnold Schwarzenegger. And this is my friend, Vpu . I presume you and Vpu haven't met, as you recently repeated in an interview with World magazine the same sentiment you gurgled ad nauseum in 'Edge of Evolution':

"Like malaria, HIV is a microbe that occurs in astronomical numbers. What's more, its mutation rate is 10,000 times greater than that of most other organisms. So in just the past few decades HIV has actually undergone more of certain kinds of mutations than all cells have endured since the beginning of the world. Yet all those mutations, while medically important, have changed the functioning virus very little. It still has the same number of genes that work in the same way. There is no new molecular machinery. If we see that Darwin's mechanism can only do so little even when given its best opportunities, we can decisively conclude that random mutation did not build the machinery of life."

I find it rather difficult to believe that you two haven't crossed paths, as Vpu turns up in a simple Google search. And as a matter of fact, Vpu is sitting right there in the totally unnecessary and worthless diagram in 'Edge of Evolution'. See? Right there:

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If you had taken the time to label this pointless diagram, you might have noticed your error, and we wouldn't need to have this conversation. Alas, Vpu is a tiny molecule, and he's easy to overlook if you don't want to see him.

Vpu, is in fact, a new gene1. 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. 2

Ah, Michael Behe, you might try to talk your way around Vpu now (though you were evidently unaware of its existence moments ago) by insisting that it is not *new* new. "Sure it's new in chimpanzees, but its not *new* in HIV-1!" Sorry, you'll find no escape with that limp-wristed, ad hoc parry. 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.

Turns out a LOT of evolution has been going on in HIV-1 since it was transferred to humans 50-60 years ago. What are the biochemical implications of these differences?

In humans, there are two functions of Vpu5-- One is inducing the degradation of CD4 molecules. CD4 is the host cell receptor HIV needs for infection. Removing CD4 from the cell surface prevents superinfection (more than one virus infecting the same cell) and helps prevent newly released viruses from turning around and infecting the same cell (also prevented by an HIV maturation step involving protease). 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.

The second function is to act as an ion channel in the host cell plasma membrane6. Five Vpu proteins come together to form a Na+K+ viroporin 7. This has been shown to assist in particle release, making the cell charge more conducive to the release of new particles. This involves the evolution of more protein-protein interactions--the individual Vpu proteins must interact to form the pentamer, plus an action site that can be used to block ion flow 8.

Viroporin capabilities have not been found with SIVcpz Vpu. Knowing what we know about Vpu, this is not surprising. If you scramble the transmembrane region of HIV-1 Vpu (the portion responsible for the ion channel formation), viral release is crippled9. And when you compare AA homology between SIVcpz and HIV-1 Vpu in the transmembrane region is unremarkable (roughly two)--that's as good as a 'scramble'. So theoretically, ion channel formation evolved in HIV-1 when it infected humans to overcome a species specific and cell specific host factor 10. Though the list of viroporins discovered is continually growing, the evolution of a viroporin de novo is not menial task.

This seems like a pretty significant biochemical change in HIV-1, to me.

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 11. Different ways of performing similar tricks with totally different amino acids. I think that's biochemically significant as well.

Ah, Michael Behe, you might try to talk your way around Vpu NOW by saying, "Vpu might be *new* new in HIV-1, but its not *NEW* *new* new. It hasnt changed in HIV-1 since humans acquired it!"

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 subtypes12

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.

So heres a quick time-line for the evolution of impossible genes and impossible protein-protein interactions, courtesy of Ian Musgrave (one of those dreadful PhDs/Professors that has something to teach this pre-grad student):

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Michael Behe, as a courtesy to you, this essay isn't even going to touch Vpx, a gene specific to the HIV-2 and SIV sm lineage. Vpx is one of those pesky gene duplications you say don't exist in HIV (Vpr x2). I also won't point out how silly it is of you to claim HIV has not evolved biochemically, when the HIV research community has barely scratched the surface of HIV's biochemical evolution (for the love of Pete, we don't even know what HIV-1 Subtype Cs gp120-gp41 look like!).

Look, the fact of the matter is, all of this information on Vpu is publicly available. No one was hiding this information. This wasn't a 'trick.' Vpu was not discovered yesterday--it was discovered in 1988. There is no excuse for you to write an entire book on the premise of HIV not being able to do something, when it is clear that these impossible feats did happen. This is just one of a billion plus examples of lazy Creationists taking advantage of the ignorance of their followers. I'm just a friggen pre-grad student who knew what the HIV-1 genome looked like and had a few minutes to do a PubMed search. I haven't even taken a course in biochemistry.

*sigh* So lets hear it, Behe, what's your excuse for missing this? Go ahead--run off to PubMed and find a paper to pubjack. I'm not going anywhere.

1. A novel gene of HIV-1, vpu, and its 16-kilodalton product
2. Diversity and Evolution of Primate Lentiviruses
3. Genetic organization of a chimpanzee lentivirus related to HIV-1
4. LANL HIV Sequence Database
5. The HIV-1 Vpu protein: a multifunctional enhancer of viral particle release
6. The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release
7. The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels
8. Drug-protein interaction with Vpu from HIV-1: proposing binding sites for amiloride and one of its derivatives
9. Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells
10. HIV-1 Vpu Promotes Release and Prevents Endocytosis of Nascent Retrovirus Particles from the Plasma Membrane
11. Vpu-mediated CD4 down-regulation and degradation is conserved among highly divergent SIV(cpz) strains
12. Molecular characterization of the HIV type 1 subtype C accessory genes vif, vpr, and vpu
13. Identification of a region within the cytoplasmic domain of the subtype B Vpu protein of human immunodeficiency virus type 1 (HIV-1) that is responsible for retention in the golgi complex and its absence in the Vpu protein from a subtype C HIV-1


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Abbie - I think this post was why and when we [s] all fell in love with you [/s] . I mean, learned to respect your posting abilities and scientific acumen.

"Ah, Michael Behe, you might try to talk your way around Vpu now (though you were evidently unaware of its existence moments ago) by insisting that it is not *new* new. "Sure it's new in chimpanzees, but its not *new* in HIV-1!" Sorry, you'll find no escape with that limp-wristed, ad hoc parry."

Beautiful words. sniff, sob, tears of joy...

and the SEED overlords are letting me have 4 reposts a week

They think they can place restraints on the greatness of ERV? I suspect they have some Reality Therapy coming their way.

By Bayesian Bouff… (not verified) on 01 May 2008 #permalink

I'm too old to fall in love with you, ERV, but I'd be glad to adopt you just so I can bask in the reflected glory.

(J-Dog, would you pass me the hankies?)

James 2:24

Simply and absolutely brilliant. ERV, your elegant explanation is a thing to be admired.

I forget exactly what the backup situation was, but if for some reason you eventually need da backups, I has 'em.

By Shirakawasuna (not verified) on 01 May 2008 #permalink

I discovered you through Pharyngula, and was instantly struck by your combination of Sagan-like scientific lyricism and twenty-something contemporary snark - and by the fact that those two diametric opposites somehow worked to brilliant and marvelous effect. A fan ever since.

You need to write a book someday. It would be something to behold, especially if you put FuckUpTheKids' comment about you being "the most hateful, frothing, foul-mouthed bitch in the blogosphere" as a blurb on the dust jacket :-D

Ya know, I can't remember how I found your blog, I think I was jumping around various anti-creationist site links after a slashdot post related a story of political deceit from them, but I do remember this is one of the first few posts I read and one of the ones that cemented myself as a reader here.

I might not get all the science, but I've started learning again since coming here, and humor in these types of posts is too good to pass up.

I think even if I found science far too confusing to be worth learning I'd keep reading just for these posts, thankfully I don't think that and enjoy basically everything here. In the end the only thing I can suggest for improving your blog can be communicated best in a language I believe you're quite familiar with and goes something like this, "I can has moar?"

Seriously, keep up the good work.

By Felstatsu (not verified) on 02 May 2008 #permalink

Abbie - not sure what all of that means (I'm an architect not a scientist) but its far more impressive/compelling than anything Behe, Dembski or any other DI fool could conjure up.

Great post, you've got a new follower.

This was the bait for me as well. Nice to see it infesting your blog again, even if it isn't a *new* new post.

By Torbjörn Larsson, OM (not verified) on 05 May 2008 #permalink

Yup, I think this was what reeled me in, too (when PZed linked you). Didn't hurt to read it again since I never paid any attention in prot/bio-chem &c &c.

Which is why I have to ask what the "gp120-gp41" is?