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Tag: Pigmentation
Pigmentation: the simplest of complex traits not so simple?
Image credit: Muntuwandi
One of the pitfalls about talking about genetics, especially human genetics, is that the public wants a specific gene for a specific trait. Ergo, the “God gene” or the “language gene.” In some cases science has been able to pull a rabbit out of the hat, and offer up a gene for a trait. But in most of those instances these are going to be single gene recessive diseases. Not exactly what the doctor ordered. In other cases the association seems trivial. For example, wet or dry earwax?* What people are truly interested in are the genetic basis of complex traits, such as intelligence, personality, and height. Unfortunately complex traits often have a complex genetic basis. A trait such as height, which is highly heritable (i.e., most of the variation in the population is due to variation in genes), turns out to be subject to the control of innumerable genes, each of which has a small impact on the value of the final trait. Then there is the possibility that the heritability is tied up to interaction effects across genes.
Europeans got less shaded in stages
The Pith: the evolution of lighter skin is complex, and seems to have occurred in stages. The current European phenotype may date to the end of the last Ice Age.
A new paper in Molecular Biology and Evolution, The timing of pigmentation lightening in Europeans, is rather interesting. It’s important because skin pigmentation has been one of the major successes of the first age of human genomics. In 2002 we really didn’t know the nature of normal human variation in skin color in terms of specific genes (basically, we knew about MC1R). This is what Armand Leroi observed in Mutants in 2005, wondering about our ignorance of such a salient trait. Within a few years though Leroi’s contention was out of date (in fact, while Mutants was going to press it became out of date) . Today we do know the genetic architecture of pigmentation. This is why GEDmatch can predict that my daughter’s eyes will be light brown from just her SNPs (they are currently hazel). This genomic yield was facilitated by the fact that pigmentation seems to be a trait where most human variation is controlled by half a dozen genes. In contrast, height or I.Q. are controlled by innumerable genes.
Mendelism is not magic
Michelle points me to this article in The Lost Angeles Times, The Colors of the Family:
I was holding my 1-year-old, ambling about downtown with some friends. White friends. She must have thought my boy belonged to one of them.
There’s a simple explanation: I’m black but my son, Ashe, is white. At least he looks it.
But things are more complicated than that.
I’m actually half black and half white. It should come as no surprise, though, that even as sophisticated as we’ve become about people of mixed parentage, I’m pigeonholed as black. If someone asks and I don’t have time to go deeper, that’s what I call myself.
Ashe is mixed too. His mother, my wife, Vanashree, is half white and half South Asian, with roots in India. She has olive skin, and Ashe is slightly lighter than she is.
This surprised us. When Ashe was born, one of the first things I said to Vanashree was, “Honey, he’s so light!” We chuckled, poking fun at our assumptions.*
But it still adapts!
Dienekes and Maju recently pointed to a paper, Contrasting signals of positive selection in genes involved in human skin color variation from tests based on SNP scans and resequencing, in Investigative Genetics. Skin color is an interesting trait because it’s one of the big “wins” in human genomics over the past 10 years. To a great extent we now know with reasonable certainty the genetic architecture and the loci responsible for most of the between population variation in pigmentation in humans. This is sharp contrast to the situation in the year 2000. Yet this result was foreseeable decades ago. Here’s what I said 5 years ago:
About two months ago I posted an entry where I sketched out an extremely simple model for skin color assuming there were 6 loci and two alleles (on and off). There was a reference in the comments to “5 loci” for skin color as a quantitative trait. From what I can gather that assumption derives from a paper published in 1981 by Russ Lande, which is online. In reality that paper simply draws upon older work from 1964, and its primary focus is on estimating the number of loci in crosses between heterogenous populations (using inbred lines was the way pioneered by Sewall Wright). But, it turns out that Cavalli-Sforza and Bodmer discuss that older work in Genetics of Human Populations, which I have a copy of. Today genomics is exploring the details of the loci which control for skin color, but we have a long way to go, so I’m going to reproduce some of the data and conclusions from Bodmer & Cavalli-Sforza’s work so that it will be online….
I’m laughing at the “we have a long way to go” part. Long way in this case probably meant a few years, as I don’t think there’s been that much substantive change since about 2008 in human pigmentation genetics. All the low hanging fruit has been picked. It looks like that across any two distinct inter-continental populations you’ll be able to apportion most of the variance to less than half a dozen loci. Geneticists were able to infer this decades ago based on pedigree analysis, which was only possible because of the fact that these were large effect quantitative trait loci in the first place (i.e., most of the variation was due to only a few genes). * If the trait had been extremely polygenic they’d only have been able to say with any plausibility or precision that the number of genes responsible was very large.
Mixed-race people are mildly complicated
I was pointed today to a piece in the BBC titled What makes a mixed race twin white or black?. The British media seems to revisit this topic repeatedly. There are perhaps three reasons I can offer for this. First, it tends toward sensationalism. Even though the BBC is relatively staid, when it comes to science it converges upon the tabloids. Second, because the number of non-whites in Britain is relatively small, there is a higher proportion of intermarriages between minorities and the white majority (from the perspective of minorities). This is especially true of people of Afro-Caribbean ancestry. So of the proportion of minorities a larger fraction are recently mixed in Britain than in the USA. Finally, the United States has a more complex attitude toward race relations than the United Kingdom, because the former has traditionally had a large non-white minority while the latter has only had so since the years after World War II. I suspect that “black-white twins” stories would seem in bad taste on this side of the pond, and bring up certain memories best forgotten.
Now, there are fallacies, confusions, and misleading shadings, in the BBC piece. I’ll hit those first before reviewing what’s going on here when fraternal twins exhibit totally different complexions.
Why Melanesians are blonde resolved?
Sort of and possible. I’ve been talking about this for years, and Greg Cochran points me to an abstract at the human genetics conference referenced earlier. Novel coding variation at TYRP1 explains a large proportion of variance in the hair colour of Solomon Islanders:
The Solomon archipelago comprises over 1,000 islands located east of Papua New Guinea and has a population noted for wide variation in hair pigmentation. 1200 samples were collected from 16 centres and hair colour measured in donors by spectrophotometer. Analysis of 589,241 single nucleotide polymorphisms across a subset of 42 dark haired and 43 blond haired individuals revealed a signal for pigmentation driven by 27 markers on 9p23 at the TYRP1 gene (rs13289810…). There were no systematic differences in ancestry between dark and blond haired participants indicating that this variation is unlikely to be due to recent introgression from other populations. Sequencing of TRYP1 showed complete conservation of this locus bar nucleotide 5,888(NG_011750), which was homozygous C in dark haired individuals and T in blonds. The resulting CGC->TGC missense mutation changes the 93 amino acid in exon 2 from an Arginine to a Cystine. Genotyping of TYRP1(93C/T) in all samples and analysis showed that in a recessive model including sex, age and local geography, there was a -1.67(-1.76, -1.50) standard deviation difference in hair colour by genotype groups (p=3.5e-106) equating to ~40% variance in this trait. Genotyping in the Human Gene Diversity Panel showed TYRP1(93C/T) to be essentially private to the Solomon Islanders…In humans, complete loss of function for Tyrp1 is known to cause rufous albinism. This is one of the only examples of a genomewide association study implicating causal variation directly, of a common local variant of functional effect being absent in other human populations and is one of the largest phenotypic effects attributable to a common polymorphism. Reasons for the maintenance of this variation are unclear, however this finding prompts the notion that we may find other large (disease causing) effect variants that are population specific and that our results are a call to arms to expand medical genomics to underrepresented populations.
Australian Aboriginals are not present in the HGDP panel, so there is no clarity on blondism in those populations, or amongst other indigenous groups in Southeast Asia and Oceania. If these are deep ancient variants then this may span all these populations. If not, then you see independent occurrences of a phenotype which is only present in Europeans and European-derived/admixed populations elsewhere. Why? One hypothesis I’ve thrown out is that it is possible that the expansive of agriculture populations erased a great deal of past human phenotypic diversity, due to the demographic growth of small initial founding groups ~5-10,000 years ago.
The question mark in the title by the way is that just because we characterize the genomic architecture of a trait, we don’t understand why it is distributed in the way it is. Perhaps small populations resulted in more genetic drift in Oceania than elsewhere? Or there is selection on the TYRP1 locus, and this trait is a side effect?
To gain pallor is easier than losing it
John Hawks illustrates what can be gained at the intersection of old data and analysis and new knowledge, Quote: Boyd on New World pigmentation clines:
I’m using some statistics out of William Boyd’s 1956 printing of Genetics and the Races of Man[1]. It gives a good accounting of blood group data known more than fifty years ago, which I’m using to illustrate my intro lectures. Meanwhile, there are some interesting passages, from the standpoint of today’s knowledge of the human genome and its variation.
On skin pigmentation – this is the earliest statement I’ve run across of the argument that the New World pigmentation cline is shallower than the Old World cline because of the relative recency of occupation….
Looking at what was said about pigmentation generations ago is of interest because it’s a trait which in many ways we have pegged. See Molecular genetics of human pigmentation diversity. Why humans vary in pigmentation in a deep ultimate sense is still an issue of some contention, but how they do so, and when the differences came about, are questions which are now modestly well understood. We know most of the genetic variants which produce between population variation. We also know that East and West Eurasians seem to have been subject to independent depigmentation events. We also know that some of the depigmentation was relatively recent, probably after the Last Glacial Maximum, and possibly as late as the advent of agriculture.
On the New World cline, which is clearly shallower than that of the Old World. The chart below from Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms is useful:
Blondes of the 'black islands'
Recently I was looking for images of the alpine biomes of the New Guinea highlands* and stumbled onto some intriguing, though not entirely surprising, set of photographs of individuals from Papua New Guinea. They were noteworthy because they manifested the conventional Melanesian physical type, but their hair had a blonde cast to it. For example, here is a charming blonde boy. The photographer has several other striking portraits of Melanesians with lighter hair at his website. In regards to the peculiar hair color of these people he says: “When you ask the people why there are so many blonde people on the islands, they answer 3 things: they have white ancestors, they receive too much sun, or they do not eat enough vitamins! – Langania village, New Ireland, Papua New Guinea.” There is more discussion in the comments about this issue, some claiming that likely it is the sea water and sun which is producing bleaching naturally. If you look around you will see references to bleaching of hair among some of these people as a cultural trait, though the references tend not to be concrete (many clearly assume they’re bleaching their hair, rather than reporting bleaching). The blonde being at the tips from what I can tell in some cases I certainly don’t reject the explanation that bleaching is a cultural practice among these peoples, albeit for children and women only.
But the peculiar hair color of these populations is noted in the scientific literature as if it is a biological characteristic of these groups, not a cultural artifact. From Molecular genetic evidence for the human settlement of the Pacifc: analysis of mitochondrial DNA, Y chromosome and HLA markers: “The Tolais of New Britain are phenotypically ‘Melanesian’, with fairly dark skin and frizzy hair, some-times almost blonde as in some highland Papuan groups.” Enter Tolai ‘New Britain’ into Google Images and the first few pages have several instances of blonde children, including this cute triplet.
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