Neanderthals came in all colors

By Razib Khan | March 19, 2012 8:48 pm

There’s a report in Science about a new short paper about Neandertal pigmentation genetics. The context is this. First, in 2007 an ingenuous paper was published which inferred that it may be that Neandertals had red hair, at least based on an N = 2 from two divergent locations. The new study looks at three Croation samples, and reports genotypes which are correlated with a swarthier phenotype in modern populations. But the results are neither here nor there: everyone interviewed in the paper assumes that like modern Europeans Neandertals were a polymorphic set of populations when it comes to pigmentation. There are lots of reasons for this agreement, despite issues one might take with this paper.

The report on the paper in Science has two sections which I want to zoom in on. First, “Nearly 60% of the formula’s predictions matched the subjects’ actual physical appearance, the authors say. The team considers that accuracy rate satisfactory, given the complexity of the genetics behind skin color and other physical traits.” Do you consider 60 percent satisfactory? What curve are you grading on? I’m willing to bet that the reporter didn’t consider 60 percent satisfactory, and neither do I. If you look in the paper you’ll see that their method predicts that a Yoruba in the HGDP sample has blue eyes and red hair. Several of the Papuans are predicted to have blue eyes.


But I also think that the Science piece did not do justice to what we know about pigmentation genomics, which is a lot. Case in point: “A particular form of the gene known as TPCN2, for example, bestows brown hair in modern humans; any other form means hair that’s another color.” Since the reporter is probably not an expert someone must have fed them this information. Or, the reporter distorted the researcher’s meaning. Because this is totally misleading. There are SNPs on this locus which correlate with brown vs. blonde hair, but my blonde father-in-law shares the same genotype as some of my siblings (who have black hair). The effect of this variant is strongly conditional upon other variants. (I looked at the same SNPs they did in the paper)

The scientists themselves sometimes have a problem communicating. For example:

…He argues that some pigmentation genes have such a powerful effect that they override the combined contributions of many weaker genes—a phenomenon that would render the new study’s simple gene addition inaccurate. The lighter skin color seen in Europeans, for instance, is due almost entirely to a single gene, he says. “We know that there are some genes that have a very strong effect” on physical appearance, he says.

This is artlessly rendered. If light skin in Europeans was due to a single gene of large effect then ~20 of African Americans would have nearly white skin (assuming dominant effect, it would be 4% if it was recessive). There are two candidate genes which come to mind as possibilities for what might make Europeans white in the mind of this researcher. The first is SLC24A5, a locus which is nearly disjoint in frequency between Europeans and Africans. This locus alone can explain 25-40% of the between population difference in pigmentation. But this locus does not make you white; otherwise I would be white! I’m a homozygote for the “European” variant of the SNP at this locus which differs across populations, as are both my parents. The total frequency of the “European” variant in South Asians is probably comfortably above 50%. A better candidate would be a SNP on SLC45A2 which is present in high proportions in European populations (~90 percent within Europe, ~10 percent in South Asia). But observe that this allele on SLC45A2 is not sufficient for light skin.

To better understand what’s going on here one just has to keep in mind how we now know pigmentation genetics works. It is most definitely not a single gene trait. But neither is pigmentation highly polygenic in the same manner than height or intelligence are. Rather, the genetic architecture of pigmentation is finitely comprehensible. For example, you could explain more than 90 percent of the between population variation between Africans and Europeans in complexion by the differences on just 5 genes. If you took every population in the world I would be willing to lay down a bet that over 90 percent of the between population variation in the pool could be explained by variants on 30 genes. 30 genes is a human-sized number that you can comprehend. A subtle nuance though is that there are different variants within particular genes. For example, both Europeans and East Asians have derived mutations in the OCA2 gene which seem to result in lighter skin, but they’re on separate mutations.

Another phenomenon to keep in mind is that the effect size of the variants seems to exhibit a power law distribution. One or two variants explain an outsized proportion of the difference, a few more a modest proportion, while many others occupy the long tail which explains less than 10 percent of the distribution. In other words, the state of just a few variants can give you a sense of the pigmentation of a population.

To bring it back to Neandertals, another issue is that this human lineage flourished for at least ~100,000 years. The best recent work on natural selection in humans implies that pigmentation can change on the order of ~10,000 years, in particular from dark to light. It would be totally unsurprising if Neandertals were polymorphic in the trait, and, they evolved toward a lighter condition for whatever reason several times, just as modern humans have. But just because we know this general truth does not mean that we have a good grasp of specific aspects of the phenomenon.

  • Clark

    If there was mixing with humans at some stage might that have affected pigmentation? (Do we have an idea of when big human pigment differentiation evolved?)

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    #1, light skin is likely to have evolved recently among eurasian populations. and independent in the east and west. the largest effect genes exhibit signatures of having swept up frequency >10,000 years B.P.

  • DK

    what we know about pigmentation genomics, which is a lot.

    Not according to the paper’s Abstract:
    “We compared predicted and observed phenotypic data through an analysis of 124 single nucleotide polymorphisms in 33 genic and seven intergenic regions … for the molecular predicted versus observed phenotypes, the percentage of agreement was as follows: freckles: 91; skin: 64; hair: 44; eyes: 36″.

    To me, this is a stark illustration of how little sense of the genomic data we can make so far: with something as simple as hair color, an analysis of 124 markers known to be involved in pigmentation does not get one even a 50% chance of getting it right. A single trait, geographic origin, would have afforded a lot better than that (globally, at least). So, what does the analysis miss? More markers? Larger N? Or could it be that epistasis is a key after all? As in “the effect of this variant is strongly conditional upon other variants”?

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    #3,

    the prediction algorithm was kind of weird. other papers have better ones. if you read this paper i think you’ll see what i mean. weighting the markers would probably have helped.

    also, we know a lot on the population level. but most of the stuff isn’t focused on individual prediction.

    btw, there is some epistasis in eye color.

  • Eurologist

    I bet makra-sha dollars that Neanderthals had more than an order of magnitude longer time to adept to the vitamin D – folic acid conundrum than incoming modern humans from the subcontinent, and almost an order of magnitude longer than extant modern humans at northern latitudes.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    and almost an order of magnitude longer than extant modern humans at northern latitudes.

    though do note that sapiens sapiens seems to always have had a more northern frontier in its range than sapiens neanderthalis.

  • http://3lbmonkeybrain.blogspot.com/ Mike Keesey

    #5, a longer time, yes, but lower population numbers, right? That counts for something, doesn’t it?

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    #7, i think perhaps a bigger issue is that there may have several extinction events, and sapiens neanderthalis repopulated their range from a refugia.

  • Bobby LaVesh

    How complete a DNA sample of individual Neanderthals do we have?

    I know there would be all sorts of ethical reasons not to, but do we have enough to attempt cloning- inserting Neanderthal DNA into a modern human egg? (not that we would). The way scientists hope to one day put Mammoth DNA into an Elephant’s egg to clone it. (from what I understand- we’re more closely related to Neanderthals than Mammoths are to modern Elephants).

    I hope one day computer simulation might be able to predict an organism from it’s DNA- may be many decades away- but it would be nice to be able to see what would be, without the associated ethical problems.

  • jb

    Razib, do you know how many individual Neanderthals we have genomes for now, and how many we are likely to end up with in the long run? My understanding has been that the number of individuals for which we have remains of any sort isn’t huge, or growing very fast, and that most of those remains aren’t in good enough condition to get usable DNA from, but the Science report ends by talking about “hundreds of individual paleopopulations,” and I’m not sure what they are referring to.

  • John Roth

    John Hawks has also weighed in on this paper. He says it doesn’t correspond with what he’s getting.

    http://johnhawks.net/node/28616

  • Justin Giancola

    Just come out with already Razib! Did you marry a Finn?! ;p Many suspect you are a Finnophile, ha ha!

  • imnobody

    If Neandhertals breed with modern humans, didn’t they belong to the same species than us?

    This guy thinks so.

    http://johnhawks.net/weblog/topics/evolution/species/species-problem-gibbons-2011.html

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This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!

About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com

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