Gene Expression

Native American HLAs, part II

Greg Cochran’s comment below is worth turning into a post:

There’s more to it than that. Tribes often have extremely limited HLA variation, contain only a small subset of the variation that you see in a wider set of Amerindians. Whereas in the old world, even little tiny groups with very low gene flow have lots of different HLA alleles. [Cavalli-Sforza 1994] You’d think that they’d lose those rare alleles by drift, but they don’t – has to be frequency-dependent selection, the same force that has kept alleles around for tens of millions of years. But in the Americas, it appears that those frequency-dependent forces simply did not exist. [Slatkin and Muirhead, 2000]

So, two things going on, which may or may not modify your conclusions. First, a bottleneck, probably: afterwards, a world in which HLA simply does not matter.

We talked about this subsequent to this comment. Basically in small populations subject to a lot of random genetic drift HLA diversity still remains high because stochastic factors run up against powerful negative frequency dependent selection effects. That is, the rarer the allele, the stronger its fitness advantage. So, as drift drives an allele frequency down it begins to run up against countervailing selective pressures. Just as drift is about to run an allele to extinction the break is slammed and it will “bounce back.” This is why HLA variants seem to be almost immortal fragments of the genome.

So what happened with Native Americans? Greg’s point seems to be that Native American groups were not subject to this particular dynamic where HLA is kept diverse within groups, so convential genetic forces of drift were far more powerful on these loci than in other human groups. What’s different? One could posit things like density of population, but the HLA have deep roots well before our own species.

Comments

  1. #1 NuSapiens
    April 26, 2006

    Maybe there just weren’t many pathogens in the Trans-Beringian Corridor, so natural selection maintaining HLA diversity was weak. Meanwhile, the founder population experienced a bottleneck.

  2. #2 razib
    April 26, 2006

    the crucial point that greg is pointing to is that HLA diversity is lower within group than is the normal when compared to a meta-population context. that is a suggestion that selection is not very powerful….

  3. #3 Ron
    April 26, 2006

    I almost cringe to say it because i have argued against it, but here the issue of zoonotic disease and the relationship to domestic animals in old vs new world may have something to do with those selective forces…?

  4. #4 David Boxenhorn
    April 26, 2006

    I, too, noted the importance of that comment. It would also explain why Eskimos didn’t re-introduce diversity, without resorting to implausible levels of genetic isolation.

    And, it makes multiple (but small) waves of immigration more believable.

  5. #5 razib
    April 27, 2006

    I almost cringe to say it because i have argued against it, but here the issue of zoonotic disease and the relationship to domestic animals in old vs new world may have something to do with those selective forces…?

    yes, but there weren’t domestic animals in the old world before 10,000 BP. the key is that there’s something weird that wasn’t weird for 30 million years in the hominid/primate lineage in the new world! it can’t be pop density, it can’t be domestic animals, etc. one issue might be that local pathogens take time to adapt to a new species, and that eventually native americans would have generated their own endemic load of human-adapted parasites in the new world which lived part of their life cycle in local animals. it might be that the ‘native american situation’ is common when humans invade a new area, but that native americans were only around for 10,000 years so the parasites didn’t catch up.

    objections

    1) parasites evolve fast. i’m wary of using the “not enough time” argument

    2) a lot of bugs pretty much hang around only in humans, and the native americans should have brought them (they did bring some)

  6. #6 David Boxenhorn
    April 27, 2006

    it can’t be pop density

    Why not? The population density for the first few thousand years must have been very low even by hunter-gatherer standards.

  7. #7 razib
    April 27, 2006

    Why not? The population density for the first few thousand years must have been very low even by hunter-gatherer standards.

    why? i doubt it was low for the first few thousand years, geometric rates of pop. growth and all. humans were probably ‘feral’ in the new world before they managed to eat/kill all the easy prey. in any case the population density measure isn’t even humans, it is large mammals over the last few tens of millions of years (this is how old most of the HLA alleles are). humans are pretty thick on the ground, so i think the pop density low bound is pretty low….

  8. #8 NuSapiens
    April 27, 2006

    OK, how about this. Same scenario I proposed above, but multiple immigrations. Low pathogen load in Trans-Beringian Corridor. Result: selection maintaining HLA diversity is weak in relation to genetic drift. Probably low pop density as well.

    I just imagine a stray group of Chukchi-like folks here and there getting caught in the corridor, and moving towards Alaska for whatever reasons (probably following big game), and then staying in the East. As climates incrementally south looked more favorable, they move south.

    Question: is there any geographic structure to Amerind interpop HLA diversity?

  9. #9 NuSapiens
    April 27, 2006

    In the domestic animals department: It’s known that Native Americans had their own breeds of dogs, presumably brought from Asia. Chihuahuas are one surviving breed of partly Amerind-breed ancestry.