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paleoanthropology, genetics and evolution

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  • "I yam what I yam"

    Wed, 2010-07-07 00:28 -- John Hawks

    NEANDERTHAL MALES HAD POPEYE-LIKE ARMS

    This isn't normally the kind of story -- oh, who am I kidding? I love to snark on these kinds of stories!

    "Popeye-like arms". Hmmmm....

    Popeye the sailor man

    Neandertals had a low brachial index -- that is, with a short forearm were relative to the humerus. Popeye, well, you can see that he has the brachial index of a giant ground sloth. Neandertals were not built like Popeye.

    The article itself reports the ideas of a group of Russian scientists, who think that hormonal changes may explain the Neandertal pattern of muscle development and cortical bone strength.

    Remains of an early Neanderthal with a super strong arm suggest that Neanderthal fellows were heavily pumped up on male hormones, possessing a hormonal status unlike anything that exists in humans today, according to a recent paper.

    ...

    The mixture [of big muscles and highly mineralized bones] is puzzling, because "Neanderthals demonstrate a markedly androgenic constitution," meaning they seemed to have a lot of steroids, yet these same hormones can cause reduced mineralization.

    As a result, the researchers say "Neanderthals were characterized not only by peculiar biomechanical adaptations, but also by a specific hormonal condition which has no close parallels among modern human hormonal conditions either normal or pathological."

    There's no mechanism being proposed here, the androgen system has effects all over the body. This is not a testable hypothesis, it's really just a speculation.

    Or is it? The cool thing about having a Neandertal genome is that in principle we can look for differences in systems like the androgen receptor pathway. Looking for coding changes in androgen-associated genes is really just a browser window away.

    So I did some checking.

    Now, let me put some caveats here. This is good blog material, but the Neandertal genome sequencing has not reached a point where we can be at all certain about mutations. There are many gaps with no coverage at all in any Neandertal individuals. Most of the sequence of human coding regions is covered by at least one read, and a good fraction of sites have multiple Neandertal reads. As I've been looking through sequence, I tend to think a site may be interesting if it has a change in the Neandertal relative to the human sequence, and if it's not near the end of a read. If the same change is present in multiple Neandertal reads, that makes it a good candidate for a genuine change in Neandertals relative to the human sequence. A large fraction of those Neandertal-specific changes actually aren't Neandertal at all. They're shared with chimpanzees and represent new human-specific changes. Many of those are SNPs in humans where the genome draft has the derived version; there are also sites where the Neandertal shares a derived SNP allele with some other humans. Then there are ones not in chimpanzees or humans, which might be Neandertal-specific alleles or substitutions.

    Looking at the androgen receptor gene and the 5-alpha-reductase gene, both central to the androgen pathway, there aren't any interesting-looking sites in the Neandertal sequencing reads. I don't think the data refute the hypothesis that the Neandertals were like humans for these genes. That's just a little bit of looking, of course, and that particular fishing expedition wasn't likely to turn up anything new. But that's the point! We shouldn't just go off speculating about fundamental changes in hormonal biology in Neandertals anymore. We can look.

    That is just the beginning of answering a question like this. To test the hypothesis, we'd want to check many other genes that lie between the androgen receptor and its final effects on gene transcription. And of course, coding changes aren't the whole story of evolution in Neandertals. Promoter and enhancer changes, or even alternative splicing changes, may be more important than coding changes, especially for a system so broadly represented in different tissues. They're harder to look for by just firing up the genome browser.

    But even these kinds of changes are potentially testable. It's not quite as fast as an interview with a reporter, but it doesn't take days to look.

    Tags: 
    muscle
    Neandertal DNA
    Neandertals
    hormones

  • Hunting a myostatin SNP-phenotype association

    Wed, 2009-08-12 15:19 -- John Hawks

    I happened to be reading some literature on myostatin today and ran across a recent paper (Kostek et al., 2009).

    Conclusion: MSTN 2379 A > G and FST -5003 A > T were associated with baseline muscle strength and size among African Americans only. These ethnic-specific associations are hypothesis generating and should be confirmed in a larger sample of African Americans.

    From that description, it looks like a gene-population association in the same vein as APOE, where an Alzheimer’s risk allele predicts disease incidence well in Europeans but not Africans. Myostatin regulates muscle growth, so here the idea would be that an allele has an effect that depends on genetic background, to the extent that might effect its evolution in those populations (Saunders et al. (2006) found that myostatin has two common alleles within Africa that look like they may have been recently selected, the two alleles are rare outside Africa).

    Well, looking more deeply into the sample, we find that it’s not so impressive as it might look:

    Results: Baseline MVC was greater among African Americans who were carriers of the MSTN G2379 allele (AG/GG, n = 15) than the A2379A homozygotes (n = 8; 64.2 ± 6.8 vs 49.8 ± 8.7 kg). African Americans who were carriers of the FST T-5003 allele (n = 12) had greater baseline 1RM (11.9 ± 0.7 vs 8.8 ± 0.5 kg) and CSA (24.4 ± 1.3 vs 19.1 ± 1.2 cm2) than African Americans with the A-5003A genotype (n = 14; P < 0.05). No MSTN or FST genotype and muscle phenotype associations were found among the other ethnic groups (P ≥ 0.05).

    Those tiny sample sizes (n = 15, n = 8) come from stratifying a much larger sample (n = 645) into ancestry groups. The very large European component of that large sample (n = 509) showed no gene-phenotype associations. What’s left is a significant result (p < 0.05) considering only 23 people.

    This may not be unusual – this allele is rare in Europeans, so the two samples may be pretty close to each other in statistical power. But it’s not exactly a vote of confidence in favor of a large effect size for the allele, even within the small African-American sample.

    That’s a common story in gene-phenotype association studies. Possibly it will replicate in a larger sample – and hopefully if it doesn’t replicate, somebody will still publish the result so that we’ll know about it.

    References

       Kostek MA, et al. 2009. Myostatin and follistatin polymorphisms interact with muscle phenotypes and ethnicity. Medicine and Science in Sports and Exercise 41:1063–1071. doi:10.1249/MSS.0b013e3181930337.

       Saunders MA, et al. 2006. Human adaptive evolution at Myostatin (GDF8), a regulator of muscle growth. Am J Hum Genet 79:1089–1097. doi:10.1086/509707.

    Tags: 
    gene-phenotype associations
    muscle
    race
    genetics

  • Muscle markings, chimpanzees, and Neandertals

    Thu, 2009-02-26 09:23 -- John Hawks

    Earlier, I pointed to my new article in Slate, about chimpanzee strength compared to humans. For anthropologists, I thought I might point to a passage in one of John Bauman's articles (1926:7-9), which raises a point I remember well from graduate school:

    The last question raised by the strength of the chimpanzee seems to have been completely overlooked in the past. All anatomists place reliance upon the relative development of the various muscle attachment ridges and pits on the bones as a trustworthy indication of the strength of the owner.

    Yet anyone who will take the trouble to compare carefully the crest of the ilium of the chimpanzee with that of the human being will notice that the muscle attachment roughnesses are very markedly less prominent in the former than in the latter, yet Suzette's pulls have clearly demonstrated an immense superiority in strength of the lumbar region in the ape. Also with regard to long sustained action, a short time spent in the anthropoidal posture will convince any person that this posture calls for more taxing long sustained action of the lumbar muscles than does the erect posture of the human being.

    We certainly can not look to man's erect posture for an explanation of the smooth sharp rim of the hip bone in the anthropoid ape, why then do the usually so reliable muscle attachments fail here to correctly indicate relative strength? The discrepancy is an extremely pronounced, not a trifling one, moreover.

    Bauman then generalized to Neandertals:

    And finally, how about those interesting Neanderthal men? We customarily base our estimate of their probable strength upon the degree of prominence of their muscle attachments as observed in the fossil bones-but should not the above consideration incline us toward caution in this class of inferences, particularly when the subjects are an ancient race known to have approximated closely to the anthropoidal type in their anatomy--as well as impel the comparative anatomist to a thorough investigation into the reason for this strange discrepancy.

    The hip is not a great example, because of the architectural difference between the human and ape pelvis. Still, we can make the same general observation about other bones like the humerus, on which muscle attachments don't convey the information about relative chimpanzee strength.

    Pronounced muscle attachment sites are not evidence that Neandertals were weak; within the context of recent hominids the rugosities and robusticity of bones are probably good indicators of muscle mass. But with some increasing evidence for evolution of muscle functional properties on the human lineage, I hesitate to assume that any Pleistocene human muscles interacted with their bony attachments in exactly the same way as ours.

    The muscle attachment issue may be especially confusing in Australopithecus, where there is a substantial contrast within species between small individuals like AL 288-1 and larger individuals -- the Maka humerus comes to mind. Here's the comparison, from White et al. (1993):

    Maka (top) and AL 288-1 humeri, from White et al. 1993

    Maka is the heavily-crested humerus at the top, Lucy's slender and smooth humerus underneath. Straightforward mass difference? Or difference in activity pattern? Or both? This is not such an unusual comparison considering the variability in living hominoids, including people. But it illustrates well the kind of range of muscle marking and cresting that existed in fossil populations. The changes during human evolution would have happened upon this underlying pattern of broad variation.

    We can probably assume it's not the functional properties of muscle differing between these two specimens. But what about between Australopithecus and Homo? Or Neandertal to recent human? We already know there are differences in muscle function among human populations, in part corresponding to alpha actinin-3 allele frequencies. Genetics may be starting to make the "expensive tissue" story come down to muscle instead of gut reduction -- if I'm going to make predictions, I would say that MYH16 will not long be alone as a gene corresponding to human muscle reduction.

    References:

    Bauman JE. 1926. Observations of the strength of the chimpanzee and its implications. J Mammal 7:1-9. JSTOR

    White TD, Suwa G, Hart WK, Walter RC, WoldeGabriel G, de Heinzelin J, Clark JD, Asfaw B, Vrba E. 1993. New discoveries of Australopithecus at Maka in Ethiopia. Nature 366:261-265.

    Tags: 
    muscle
    metabolism
    chimpanzees
    osteology
    Neandertals
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Neandertals

For years, I've worked on their bones. Now I'm working on their genes. Read more about the science studying these ancient people.

Denisova

From a finger bone of an ancient human came the record of a completely unexpected population. My lab is working on the science of the Denisova genome.

Acceleration

The advent of agriculture caused natural selection to speed up greatly in humans. We're uncovering some of the ways that populations have rapidly changed during the last 10,000 years.

Malapa

Just outside Johannesburg, the Malapa site is producing some of the most exciting finds in human evolution. This site is the headquarters of the Malapa Soft Tissue Project.