SRGAP2 Duplication & Inhibition

Wednesday’s Daily Science Update comes from Dr Jeffrey Tomkins, who claims that Newly Discovered Human Brain Genes Are Bad News for Evolution. Well, he would take the contrary view to the other news coverage on this study: see, for example, The humanity switch: How one gene made us brainier in the New Scientist for an example of the other.

The genes in question are SRGAP2, along with three (partial – they are not the full gene) duplicates only found in humans. Tomkins claims that these other genes are not – and indeed could not be – duplicates, and are instead ‘unique’ (and all the rest of it). Nevertheless, problems with his article begin with the title: the genes are not ‘newly discovered’ at all.

My quick inkscape drawing of the chimp/human chromosome 1 with the genes highlighted. Click through for the abstract of the paper w/ the figure this is based on

Without further ado, here’s how Tomkins begins:

Did the human brain evolve from an ape-like brain? Two new reports describe four human genes named SRGAP2A, SRGAP2B, SRGAP2C, and SRGAP2D, which are located in three completely separate regions on chromosome number 1. They appear to play an important role in brain development. Perhaps the most striking discovery is that three of the four genes (SRGAP2B, SRGAP2C, and SRGAP2D) are completely unique to humans and found in no other mammal species, not even apes.

The first of these reports is Evolution of Human-Specific Neural SRGAP2 Genes by Incomplete Segmental Duplication (also relevant: this talk abstract), from which I adapted the above diagram, while the second is Inhibition of SRGAP2 Function by Its Human-Specific Paralogs Induces Neoteny During Spine Maturation. The latter is talking about how proteins made by the duplicate SRGAP2 genes inhibit the originals function, causing a slowing of brain development (actually a good thing). The former is about the genes evolution. I’m not sure why Tomkins finds the fact that the genes don’t appear in anything but humans to be ‘striking’ (and again, its not a new discovery). Is he conceding the widespread genetic similarities between humans and other animals, and that this is an exception?

While each of the genes share some regions of similarity, they are all clearly unique in their overall structure and function when compared to each other. Evolutionists claim that an original version of the SRGAP2 gene inherited from an ape-like ancestor was somehow duplicated, moved to completely different areas of chromosome 1, and then altered for new functions. This supposedly occurred several times in the distant past after humans diverged from an imaginary ancestor in common with chimps.

Gene duplication happens: the “somehow” is an unnecessary attempt to cast doubt wherever he can. And what makes the genes ‘unique’?

Each of the duplications were incomplete. SRGAP2B through D are only partial copies,  and this does technically make them ‘unique’. But I don’t see anything to suggest that there are major changes beyond that. There are, yes, some changes – there would need to be for the researchers to date the duplication events (to ~3.4 may, ~2.4mya, and ~1 mya) – but not quite what Dr Tomkins is implying. And their “new functions” are basically to get in the way, and I would think that they could do that perfectly well as simply imperfect copies, without significant further alteration.

But this story now wields major problems. First, when compared to each other, the SRGAP2 gene locations on chromosome 1 are each very unique in their protein coding arrangement and structure. The genes do not look duplicated at all. The burden of proof is on the evolutionary paradigm, which must explain how a supposed ancestral gene was duplicated, spliced into different locations on the chromosome, then precisely rearranged and altered with new functions—all without disrupting the then-existing ape brain and all by accidental mutations.

Again, I’m not seeing anything (admittedly I can only read the abstracts of these things) that would justify the claim that the genes are “each very unique in their protein coding arrangement and structure,” beyond the imperfect copy aspect. “The genes do not look duplicated at all” – Tomkins would be terrible at searching for plagiarised works, you could probably confound him with a thesaurus alone.

The second problem has to do with the exact location of the B, C, and D versions of SRGAP2. They flank the chromosome’s centromere, which is a specialized portion of the chromosome, often near the center, that is important for many cell nucleus processes, including cell division and chromatin architecture. As such, these two regions near the centromere are incredibly stable and mutation-free due to an extreme lack of recombination. There is no precedent for duplicated genes even being able to jump into these super-stable sequences, much less reorganizing themselves afterwards.

I’m not sure quite how close the genes are to the centromere, and how close they would need to be. By far the closest is C, which is actually even closer than I drew it above – but is it close enough?

More importantly, is what Tomkins says about the invulnerable centromeres even true? A paper (Repetitive Conundrums of Centromere Structure and Function) by one of the corresponding authors of the papers given above, Dr Evan E. Eichler, from way back in 1999 said:

The recent identification of large gene duplications in the vicinity of centromeres may be another example of the enhanced mutational lability of such regions of the genome.

Given that ‘lability’ is a synonym of “susceptible to change,” it would appear that he might even have it completely backwards.

Confident that he has proved his case, Dr Tomkins concludes:

The fact that three newly discovered genes that are completely unique to humans and found in no other known mammal species has been cleverly obfuscated in evolutionary verbiage. Clearly this is yet another major genetic discovery that invalidates human evolution and shows that we are created uniquely “in the image of God” as the book of Genesis teaches.

I can only point out that statements prefaced with ‘clearly’ rarely are.

On a (semi) related subject, this recent Nature column is quite good: Reach out to defend evolution. I’d have mentioned it sooner, but I forgot about it until now. It talks about the reaction to the Yutyrannus discovery in creationist circles, with AiG’s coverage singled out as an example of the “shrewd and calculated creationist machine”. I have a hunch that the author, Russel Garwood, did not read Brian Thomas’ article if he gave that description…

Garwood suggests pre-emptive strikes are needed:

If research is to appear that will attract an obvious creationist interpretation, an accompanying blog post could explain the work and highlight flaws in any anti-evolution attacks. Sites such as the Natural Environment Research Council’s Planet Earth Online and the Palaeontological Association-sponsored provide researchers with vehicles for one-off posts. Publishers can do more, and could offer online summaries in non-technical language, written by the researchers. The open-access journal Palaeontologia Electronica already does this.

I think that would be very useful. I also think that there is a good chance that Mr Thomas (or somebody else from the ICR) will comment on it soon. That will be funny.

(24/5) But wait, there’s more! I sent an email to both the lead (Dr Megan Dennis) and corresponding (Dr Evan Eichler, mentioned above) authors of the evolution paper letting them know about Tomkins’ article. From Dr Dennis I got a copy of both papers. Table 2 of the evo paper provides the information I needed to determine if there were any further differences between the duplicated genes so as to justify Dr Tomkins’ repeated claims that they are “each very unique.”

The highest “percent sequence divergence” between these genes is… .584%. That’s not a lot. Worse, Tomkins was prepared to concede that the SRGAP2A gene in humans is the same as the SRGAP2 gene in other animals, but the divergence there is actually higher, at .852%, though this rises as high as .960% between the chimp and the C gene. This latter finding, to round things off, is said to be “consistent with the accelerated mutation rate for these chromosomal regions.” It’s not looking good for Dr Tomkins’ claim that the region around the centromere is “super-stable.”

Dr Eichler, for his part, said: “Wow! Much of this is so wrong. Thanks for the heads up.” I think you can appreciate why by this point.

5 thoughts on “SRGAP2 Duplication & Inhibition

  1. I missed out on one of the papers you mentioned when writing my post on this mutation. I have since updated mine with the additional information, thank you for pointing it out.

    Also, I think offering summaries of research by the researchers would be a great boon to science communication. However, it would make my type of blog king of irrelevant. Since the wheels of change are often very slow hopefully I should’ve finished my degree and be able to post original thoughts by the time simply reposting research becomes moot.

    Also, whilst I hate to just pimp my blog again, I uploaded a digram of the product of these proteins.

    As you can see, they are pretty clear replications of the first protein producing the F-BAR part of it. The notion that these “do not look duplicated” is refuted by simple facts.

    • So that was the post that I was too tired to read properly. It all makes sense now…

      And I have a feeling that many researchers may lack the time or ability to write these articles. Perhaps, in the future, journals will need more than just peer-reviewers to read over the papers submitted – there might be an expansion of things like the PLoS blogging network.

    • It could as simple as having the researchers vet blogs on the subject. If they think they’re an accurate representation of their work they get a big shiny tick or something.

      There is a small room for abuse if the researcher with holds tick from a blog overly critical but given they wouldn’t be able to stop them publishing this should be no biggy.

  2. That’s quite an interesting article from Nature.
    AiG took around 10 days to comment on Yutyrannus huali (and the ICR even longer
    though they had little very to offer by comparison).


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