Razib Khan One-stop-shopping for all of my content

November 8, 2013

Selection happens; but where, when, and why?

Filed under: Anthroplogy,Genetics,Genomics,Pigmentation — Razib Khan @ 1:49 am
Distribution of SLC452 variation at SNP rs1426654. Credit, HGDP Browser

Distribution of SLC452 variation at SNP rs1426654. Credit, HGDP Browser

Nina Davuluri, Miss America 2014, Credit: Andy Jones

Nina Davuluri, Miss America 2014, Credit: Andy Jones

One of the secondary issues which cropped up with Nina Davuluri winning Miss America is that it seems implausible that someone with her complexion would be able to win any Indian beauty contest. A quick skim of Google images “Miss India” will make clear the reality that I’m alluding to. The Indian beauty ideal, especially for females, is skewed to the lighter end of the complexion distribution of native South Asians. Nina Davuluri herself is not particularly dark skinned if you compared her to the average South Asian; in fact she is likely at the median. But it would be surprising to see a woman who looks like her held up as conventionally beautiful in the mainstream Indian media. When I’ve pointed this peculiar aspect out to Indians* some of them of will submit that there are dark skinned female celebrities, but when I look up the actresses in question they are invariably not very dark skinned, though perhaps by comparison to what is the norm in that industry they may be. But whatever the cultural reality is, the fraught relationship of color variation to aesthetic variation prompts us to ask, why are South Asians so diverse in their complexions in the first place? A new paper in PLoS Genetics, The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent, explores this genetic question in depth.

Much of the low hanging fruit in this area was picked years ago. A few large effect genetic variants which are known to be polymorphic across many populations in Western Eurasia segregate within South Asian populations. What this means in plainer language is that a few genes which cause major changes in phenotype are floating around in alternative flavors even within families among people of Indian subcontinental origin. Ergo, you can see huge differences between full siblings in complexion (African Americans, as an admixed population, are analogous). While loss of pigmentation in eastern and western Eurasia seems to be a case of convergent evolution (different mutations in overlapping sets of genes), the H. sapiens sapiens ancestral condition of darker skin is well conserved from Melanesia to Africa.


So what’s the angle on this paper you may ask? Two things. The first is that it has excellent coverage of South Asian populations. This matters because to understand variation in complexion you should probably look at populations which vary a great deal. Much of the previous work has focused on populations at the extremes of the human distribution, Africans and Europeans. There are obvious limitations using this approach. If you are looking at variant traits, then focusing on populations where the full range of variation is expressed can be useful. Second, this paper digs deeply into the subtle evolutionary and phylogenomic questions which are posed by the diversification of human pigmentation. It is often said that race is often skin deep, as if to dismiss the importance of human biological variation. But skin is a rather big deal. It’s our biggest organ, and the pigmentation loci do seem to be rather peculiar.

You probably know that on the order of ~20% of genetic variation is partitioned between continent populations (races). But this is not the case at all genes. And pigmentation ones tend to be particular notable exceptions to the rule. In late 2005 a paper was published which arguably ushered in the era of modern pigmentation genomics, SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. The authors found that one nonsynonomous mutation was responsible for on the order of 25 to 33% of the variation in skin color difference between Africans and Europeans. And, the allele frequency was nearly disjoint across the two populations, and between Europeans and East Asians. When comparing Europeans to Africans and East Asians almost all the variation was partitioned across the populations, with very little within them. The derived SNP, which differs from the ancestral state, is found at ~100% frequency in Europeans, and ~0% in Africans and East Asians. It is often stated (you can Google it!) that this variant is the second most ancestrally informative allele in the human genome in relation to Europeans vs. Africans.

SLC24A5 was just the beginning. SLC45A2, TYR, OCA2, and KITLG are just some of the numerous alphabet soup of loci which has come to be understood to affect normal human variation in pigmentation. Despite the relatively large roll call of pigmentation genes one can safely say that between any two reasonably distinct geographic populations ~90 percent of the between population variation in the trait is going to be due to ~10 genes. Often there is a power law distribution as well. The first few genes of large effect are over 50% of the variance, while subsequent loci are progressively less important.

So how does this work to push the overall results forward?

- With their population coverage the authors confirm that SLC24A5 seems to be polymorphic in all Indo-European and Dravidian speaking populations in the subcontinent. The frequency of the derived variant ranges from ~90% in the Northwest, and ~80% in Brahmin populations all over the subcontinent, to ~10-20% in some tribal groups.

- Though there is a north-south gradient, it is modest, with a correlation of ~0.25. There is a much stronger correlation with longtitude, but I’m rather sure that this is an artifact of their low sampling of Indo-European populations in the eastern Gangetic plain. As hinted in the piece the correlation with longitude has to do with the fact that Tibetan and Burman populations in these fringe regions tend to lack the West Eurasian allele.

- Using haplotype based tests of natural selection the authors infer that the frequency of this allele has been driven up positively in north, but not south, India. It could be that the authors lack power to detect selection in the south because of lower frequency of the derived allele. And, I did wonder if selection in the north was simply an echo of what occurred in West Eurasia. But if you look at the frequency of the A allele in the north most of the populations seem to have a higher frequency of the derived variant than they do of inferred “Ancestral North Indian”.

What’s perhaps more interesting is the bigger picture of human evolutionary dynamics and phylogenetics that these results illuminate. Resequencing the region around SLC24A5 these researchers confirmed it does look like the derived variant is identical by descent in all populations across Western Eurasia and into South Asia. What this means is that this mutation arose in someone at some point around the Last Glacial Maximum, after West Eurasians separated from East Eurasians. The authors gives some numbers using some standard phylogenetic techniques, but admit that it is ancient DNA that will give true clarity on the deeper questions. When I see something written like that my hunch, and hope, is that more papers are coming soon.

When I first read The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent, I thought that it was essential to read Ancient DNA Links Native Americans With Europe and Efficient moment-based inference of admixture parameters and sources of gene flow. The reason goes back to the plot which I generated at the top of this post: notice that Native Americans do not carry the West Eurasian variant of SLC24A5. What the find of the ~24,000 Siberian boy, and his ancient DNA, suggest is that there was a population with affinities closer to West Eurasians than East Eurasians that contributed to the ancestry of Native Americans. The lack of the European variant of SLC24A5 in Native Americans suggests to me that the sweep had not begun, or, that the European variant was disfavored. What the other paper reports is that on the order of 20-40% of the ancestry of Europeans may be derived from an ancient North Eurasian population, unrelated to West Eurasians (or at least not closely related). It is likely that this population has something to do with the Siberian boy. Since Europeans are fixed for the derived variant of SLC24A5, that implies to me that sweep must have occurred after 24,000 years ago.

journal.pgen.1003912.g002At this point I have to admit that I believe need to be careful calling this a “European variant.” Just because it is nearly fixed in Europe, does not imply that the variant arose in Europe. If you look at the frequency of the derived variant you see it is rather high in the northern Middle East. Looking at some of the populations in the Middle Eastern panel the ancestral variant might be all explained by admixture in historical time from Africa. If the sweep began during the last Ice Age, then most of Europe would have been uninhabited. The modern distribution is informative, but it surely does not tell the whole story.

Where we are is that SLC24A5 , and pigmentation as a whole, is coming to be genomically characterized fully. We don’t know the whole story of why light skin was selected so strongly. And we don’t quite know where the selection began, and when it began. But through gradually filling in pieces of the puzzle we may come to grips with this adaptively significant trait in the nearly future.

Citation: Basu Mallick C, Iliescu FM, Möls M, Hill S, Tamang R, et al. (2013) The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent. PLoS Genet 9(11): e1003912. doi:10.1371/journal.pgen.1003912

* From my personal experience American born Indians often do not share the same prejudices and biases, partly because subtle shades of brown which are relevant in the Indian context seem ludicrous in the United States.

The post Selection happens; but where, when, and why? appeared first on Gene Expression.

August 27, 2012

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 ...

January 16, 2012

Mendelism is not magic

Filed under: Genetics,Genomics,Human Genetics,Human Genomics,Pigmentation,race — Razib Khan @ 1:23 am

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.*


Let’s get the sociological aspect out of the way. Is this really that surprising? Folk-biology has always had the concept of a “throwback,” which really distills the reality of Mendelian inheritance (as opposed to simple blending processes). In societies such as Brazil or India where there is a fair amount of segregation of polymorphisms which control skin color it isn’t that unheard of for a child to be darker or lighter in tone than both parents. And more frankly, this is not unknown within the African American community, where there is a range of skin tone due to ~20% European admixture. I suspect many African American would have these “assumptions,” because of an intuitive understanding of the unpredictable nature of the inheritance of this trait.

Second, the author of the piece is half black and half white in social terms, but there is no chance he is 50 percent African in ancestry. Barack H. Obama is 50 percent African in ancestry, but African Americans almost always have some admixture. I’ve analyzed ~150 African Americans in terms of their ancestry, and they always have some European ancestry. In fact the few Africans in my data set jump out because they lack this component. In other words, the author’s child is somewhat more than 50 percent European in ancestry.

Finally, what’s the science behind this? This isn’t that  hard to actually understand, because the genetic architecture of pigmentation has been well elucidated. Only a few genes control most of the variation across populations (the difference we see between Africans and Europeans, South Asians and East Asians). Because we know the parents’ ancestry we can make a few educated guess.es The largest effect size upon of a gene pigmentation in a given individual is probably from SLC24A5. The father is likely  a heterozygote on this at the SNP in question, with a “light” European copy, and a “dark” African one. The mother is most likely, though not inevitably, a homozygote; the frequency of the “light” copy is well north of 50 percent in South Asians (I’m a homozygote, as are both my parents). So the child has a 50 percent chance of being a heterozygote or a “light” homozygote. That’s some of the answer right there. Because the child does not have blue eyes we know that they are unlikely to be homozygote for the combination of markers which is correlated with blue eyes (probably due to a regulator element on the HERC2 locus). This is also associated with lighter complexion and hair color. But there is another locus which I think would be especially important: SLC45A2. There is a “light” variant here which is highly localized to Europeans. Its frequency is 95 percent in Northern Europe, and 15 percent in Northern India (85 percent in Northern Italy, 65 percent in Turkey, etc.). It is not found in East Asia or Africa, except in cases of clear admixture with Europeans. Europeans who are homozygote for the “dark” variant tend to be olive skinned (this genotype is relatively rare, though not unheard of in Southern Europe as per the frequencies above). Both the parents in this case would almost certainly be heterozygotes. This means that their son had a 25 percent chance of exhibiting the Northern European genotype. That is a straightforward explanation for why he might be lighter than either parent. Of course there are a few other genes of some importance, but I suspect that SLC45A2 is where most of the work is done in this case because of the backgrounds of the parents (i.e., I’m pretty sure they’re heterozygotes).

I understand that the point of the article was not the genomics of pigmentation. But to talk about social matters it sometimes pays to get the science nailed down. Like it or not this is a time in the United States where people of mixed ancestry are going to be more common. I rarely get the “Where are you from?” question anymore (because I’m not black or white), but I wonder if the “What are you?” (asked of mixed-race individuals) is going to persist a little longer.

* I think lurking within the subtext of the article is the salience of African ancestry, and the idea that it is particularly potent. The author’s wife’s background is mentioned almost in passing, before moving back to the main attraction of the child of an African American no longer appearing visibly African American. Many of the ideas of white nationalist thinkers such as Madison Grant may no longer be in vogue, but their idea that African ancestry was particular powerful in swamping out all other ancestry remains an unspoken assumption in American society.

December 4, 2011

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.

 

But it’s one thing to ascertain the genetic architecture of the trait, and another to make reasonable characterizations about its natural history. To make a long story short haplotype based tests, which look for correlations of markers across regions of the genome, tend to suggest that many of the pigmentation loci have been subjected to recent bouts of natural selection. More interestingly, the candidate genes which seem likely to account for light skin in East and West Eurasians seem to be somewhat different, implying that the change in allele frequencies postdates the separation of these two populations. A few years ago there were waves made when there was a report that the gene which seems to be responsible for a great deal of the de-pigmentation in West Eurasians, SLC24A5, only began to sweep up to higher frequencies within the last ~6,000 years. But I heard through the grapevine that this may be too much of an underestimate, and you might be looking at a sweep which began more than ~10,000 years ago.**

The results in the paper above throw some cold water on positive results for natural selection at the pigmentation loci. Why does this matter? Because a priori there are obvious reasons why there might be natural selection at these genes. In contrast, many results have to be accompanied by after the fact suppositions as to the functional rationale for adaptation. The question becomes: if you can’t trust the results to be consistent on a trait where the adaptive rationale and genetic architecture are clear, when can you trust these tests? I think the qualifying kicker in the paper above comes in the discussion:

The fifth, and perhaps most likely, reason for discrepancies between LRH [long range haplotype] and sequence-based tests we observed here may be the different underlying assumptions of the evolutionary models used (that is, instantaneous selective sweep versus incomplete selective sweeps) in the definition of each statistic, and the evolutionary timescale over which each type of test can recover departures from neutrality…In that case, our results might indicate an extremely recent selection in the pigmentation genes, which would be recovered by haplotype-based but not sequence-based tests.

In other words, the authors themselves believe i is entirely possible that the likely reason you don’t see a concordance between the results in these sets of tests is that they exhibit differing sensitives to different adaptive dynamics. This is one reason haplotype based tests became popular in the first place, as they could fix upon processes which something like Tajima’s D might miss. So at this point I think we can still say with some certainty that natural selection seems highly likely at these genes, even if they don’t jump out on all the tests.

COMMENTS NOTE: Any comment which misrepresents the material in this post will result in banning without warning. So you should probably stick to direct quotes in lieu of reformulations of what you perceive to be my intent in your own words. For example, if you start a sentence with “so what you’re trying to say….”, you’re probably going to get banned. I said what I tried or wanted to say in the post. Period.

* There are few enough SNPs that I can, and have, constructed a distribution of phenotypic outcomes of my soon-to-arrive child based on the variation present in the parents, who have both been genotyped.

** I am homozygous for the “European” allele at this locus, as are my parents. I am of the suspicious that this variant arrived in the Indian subcontinent via the “Ancestral North Indians.”

October 5, 2011

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.


It starts out somewhat ludicrously: “Her son Leo has black skin and her daughter Hope, has white skin.” This is false in a precise sense. Leo clearly has medium to light brown skin (there are photos in the piece). What’s going on here is that Leo has some African ancestry, and because of the rule of hypodescent all people of African ancestry with a shade of brown skin, from nearly black to light brown are termed “black skinned.” This is not a trivial semantic elision. If Leo truly had black skin, very dark brown, than there’d be a lot of explaining to do, because the genetics would be somewhat mystifying. More on that later.

Second:

She was adopted when she was four years old, and her birth mother is Afro-Caribbean and her British birth father was white. Her DNA tests revealed that, genetically, she was exactly 50% African and 50% European.

This is very unusual, and the results suggested that Shirley’s mother had pure African roots, and that her ancestors must have moved from Africa to the Caribbean quite recently.

Not necessarily. Mixed-race people, especially those with recent admixture, don’t have their different ancestral components distributed equally across their genome. It may be that in the process of sampling chromosomes from this individual’s Afro-Caribbean mother she received almost none of the European quantum, perhaps localized to a few chromosomal segments. This “noise” in the process explains why I seem to carry an elevated proportion of East Asian ancestry in relation to both of my parents. I simply received genetic copies sampled from the more “East Asian” regions of my parents’ genomes.

Next:

“Our skin colour is determined by a number of gene variants – at least 20 variants, I would say, probably quite a few more than that,” says Dr Wilson.

This is complicated, but I’d say that the good doctor is misleading the audience. Skin color seems to be a quantitative trait where you can explain the vast majority of between population variation with only a few genes, at most six. When it comes to European-African difference variants at two loci, SLC24A5 and KITLG can account for well over half of the difference. It is true that there are many, many, genes that effect skin color, but there is a definite distribution where the vast majority of genes tweak the trait only on the margins. In other words, there may be 20 variants (there are more), but for good predictive power at the inter-population level you’re good to go with 4 or 5.

I specify inter-population level, because within populations the gene set which can allow you to predict variation may be slightly different, and you have to take into account sex differences. For hormonal reasons males seem somewhat darker than females in human populations. Additionally, people also are palest in their youth, and become darker as they age. Finally, some of the genes which explain differences between populations are invariant within a population. Therefore the genes which are of lower effect size move up the stack. So when it comes to European-African variation, the largest effect gene, SLC24A5, won’t explain anything within these two populations. That’s because it is fixed for alternative variants (the light vs. dark conferring variants). So the second effect size may move up to first effect size when you evaluate on a smaller grain (but if the second effect size is nearly fixed, then it might drop far down as well).

Now let’s move on to the common idea that darkness dominates over lightness:

As in a painter’s palette, in the skin the presence of pigment dominates the absence of pigment, so the fact that Hope is white is very unusual.

This is hypodescent popping up again. Though in the West we live in an anti-racist age, at least notionally, it is interesting how concepts and models from a white supremacist era remain operative, at least implicitly. The idea that whites are recessive to non-whites makes totally sense if you code anyone with visible non-white ancestry as non-white. Even if they are genetically more white than not. The rationale for this model was the idea that there is a reversion to the more “primitive” type. So a cross between a black and a white produced a black, and a cross between a Nordic and a Mediterranean produced a Mediterranean. Inferiority taints the purity of superiority.

Less ideologically if you classify skin complexion into white and non-white in a dichotomous fashion then you logically consign the non-white trait to dominance. For example, if nearly, but not quite, white skin is “dark,” then you make it very difficult for someone with a substantial number of pigment conferring alleles to produce a child with very light skin.

Finally, now that we have elucidated the genetic architecture of pigmentation to a great extent we can make assessments of dominance and recessiveness on a locus by locus manner. If you plot skin complexion darkness as a function of reflectance you can turn it from a dichotomous or discrete trait to a continuous one. So individuals can have a “melanin index,” an integer value equivalent to their position on a scale of lightness and darkness. Converse to expectations above it turns out that on the two largest effect genes explaining difference between Africans and Europeans the light alleles are more dominant than the dark alleles! In other words, if the two alleles had an equal effect you’d expect a value between the two in their homozygote state. As it is, the values tend toward higher reflectance (light) than dark. I would caution that terms like “dominant” and “recessive” can be highly subjective and dependent on how you code the trait, the nature of the population you sample from in a polygenic character, or even scale the of values. So in this case you notice that switching from a dichotomous code of white vs. non-white to a continuous value corresponding to reflectance flips the model from the light trait being recessive to the dark, to the dark being recessive to the light (albeit, only mildly).

Because pigmentation is controlled by only a few genes the state at these loci are poor proxies for total genome content. In plainer language mixed-race siblings won’t deviate too much in their ancestral quantum, but they can deviate a great deal in their physical appearance. In fact, because of the poor correlation the slightly “blacker” twin in total ancestry may actually look more like a white person, and vice versa.

Now let’s go back to first principles. We’ll make some simplifying assumptions to illustrate what’s going on easily. Take 6 genes which control skin color. Assume equal effect. Each gene comes in two variants. Light and dark. Two copies of light result in a value of 0, while two copies of dark result in 2. A copy of each results in 1. In other words, the alleles are additive across a locus. Also assume that the genes are independent. They’re not linked. So the value at each gene is independent of the other genes. Finally, assume that the genes’ implied values summed together result in a total pigmentation phenotype outcome. So they’re additive across loci.

To make even simpler let’s assume that the parents are F1 African-European hybrids. That means that one of their parents’ was European and the other African. So both share the same ancestry of recent vintage. As it happens Africans and Europeans are very different on pigmentation genes, so we can assume that these parents carry one light copy and one dark copy across the six genes. This means you’d expect them to be brown.

Since they are brown, wouldn’t their children be brown? No. Not necessarily. As per Mendel’s Laws each contributes contributes one gene copy at each locus. So for the 6 loci above each parent contributes one pigmentation gene. What does that mean concretely? I Already simplified things to produce an elegant outcome: the F2 offspring could be all light, all dark, or one copy of both, like their parents, at any given gene. To illustrate what I’m talking about, SLC24A5 is disjoint in frequency across Africans and Europeans. All Europeans have one variant, and all Africans have another. So the offspring of a marriage between an African and a European will be heterozygote on that locus. If they marry another person of similar background, homozygote light and dark genotypes will resegregate out at fractions of 25% each, with half the outcome being heterozygote as in the parental condition. In other words, there are a 25% probability of a F2 child of F1 hybrids being “white” at this locus. There are 6 loci. Assuming independent probabilities, you multiply out 0.256, and get 1 out of ~4,000 that the child will be white like their white grandparents.

I ran this as a binomial 10,000 times, and here’s the distribution I came up with:

The white and black offspring don’t show up because the number of outcomes is so rare in this model, but as you can see the median outcome is brown, like the parents. But the tails are significant. In other words, don’t be surprised if there’s a lot of variation among the siblings. But why should you be? If you know of people from populations where pigmentation alleles are segregating in polymorphic frequencies, such as Latin Americans and South Asians, you are aware that different siblings can look strikingly different when it comes to complexion. Though I guess that’s a new insight for the British….

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.


It starts out somewhat ludicrously: “Her son Leo has black skin and her daughter Hope, has white skin.” This is false in a precise sense. Leo clearly has medium to light brown skin (there are photos in the piece). What’s going on here is that Leo has some African ancestry, and because of the rule of hypodescent all people of African ancestry with a shade of brown skin, from nearly black to light brown are termed “black skinned.” This is not a trivial semantic elision. If Leo truly had black skin, very dark brown, than there’d be a lot of explaining to do, because the genetics would be somewhat mystifying. More on that later.

Second:

She was adopted when she was four years old, and her birth mother is Afro-Caribbean and her British birth father was white. Her DNA tests revealed that, genetically, she was exactly 50% African and 50% European.

This is very unusual, and the results suggested that Shirley’s mother had pure African roots, and that her ancestors must have moved from Africa to the Caribbean quite recently.

Not necessarily. Mixed-race people, especially those with recent admixture, don’t have their different ancestral components distributed equally across their genome. It may be that in the process of sampling chromosomes from this individual’s Afro-Caribbean mother she received almost none of the European quantum, perhaps localized to a few chromosomal segments. This “noise” in the process explains why I seem to carry an elevated proportion of East Asian ancestry in relation to both of my parents. I simply received genetic copies sampled from the more “East Asian” regions of my parents’ genomes.

Next:

“Our skin colour is determined by a number of gene variants – at least 20 variants, I would say, probably quite a few more than that,” says Dr Wilson.

This is complicated, but I’d say that the good doctor is misleading the audience. Skin color seems to be a quantitative trait where you can explain the vast majority of between population variation with only a few genes, at most six. When it comes to European-African difference variants at two loci, SLC24A5 and KITLG can account for well over half of the difference. It is true that there are many, many, genes that effect skin color, but there is a definite distribution where the vast majority of genes tweak the trait only on the margins. In other words, there may be 20 variants (there are more), but for good predictive power at the inter-population level you’re good to go with 4 or 5.

I specify inter-population level, because within populations the gene set which can allow you to predict variation may be slightly different, and you have to take into account sex differences. For hormonal reasons males seem somewhat darker than females in human populations. Additionally, people also are palest in their youth, and become darker as they age. Finally, some of the genes which explain differences between populations are invariant within a population. Therefore the genes which are of lower effect size move up the stack. So when it comes to European-African variation, the largest effect gene, SLC24A5, won’t explain anything within these two populations. That’s because it is fixed for alternative variants (the light vs. dark conferring variants). So the second effect size may move up to first effect size when you evaluate on a smaller grain (but if the second effect size is nearly fixed, then it might drop far down as well).

Now let’s move on to the common idea that darkness dominates over lightness:

As in a painter’s palette, in the skin the presence of pigment dominates the absence of pigment, so the fact that Hope is white is very unusual.

This is hypodescent popping up again. Though in the West we live in an anti-racist age, at least notionally, it is interesting how concepts and models from a white supremacist era remain operative, at least implicitly. The idea that whites are recessive to non-whites makes totally sense if you code anyone with visible non-white ancestry as non-white. Even if they are genetically more white than not. The rationale for this model was the idea that there is a reversion to the more “primitive” type. So a cross between a black and a white produced a black, and a cross between a Nordic and a Mediterranean produced a Mediterranean. Inferiority taints the purity of superiority.

Less ideologically if you classify skin complexion into white and non-white in a dichotomous fashion then you logically consign the non-white trait to dominance. For example, if nearly, but not quite, white skin is “dark,” then you make it very difficult for someone with a substantial number of pigment conferring alleles to produce a child with very light skin.

Finally, now that we have elucidated the genetic architecture of pigmentation to a great extent we can make assessments of dominance and recessiveness on a locus by locus manner. If you plot skin complexion darkness as a function of reflectance you can turn it from a dichotomous or discrete trait to a continuous one. So individuals can have a “melanin index,” an integer value equivalent to their position on a scale of lightness and darkness. Converse to expectations above it turns out that on the two largest effect genes explaining difference between Africans and Europeans the light alleles are more dominant than the dark alleles! In other words, if the two alleles had an equal effect you’d expect a value between the two in their homozygote state. As it is, the values tend toward higher reflectance (light) than dark. I would caution that terms like “dominant” and “recessive” can be highly subjective and dependent on how you code the trait, the nature of the population you sample from in a polygenic character, or even scale the of values. So in this case you notice that switching from a dichotomous code of white vs. non-white to a continuous value corresponding to reflectance flips the model from the light trait being recessive to the dark, to the dark being recessive to the light (albeit, only mildly).

Because pigmentation is controlled by only a few genes the state at these loci are poor proxies for total genome content. In plainer language mixed-race siblings won’t deviate too much in their ancestral quantum, but they can deviate a great deal in their physical appearance. In fact, because of the poor correlation the slightly “blacker” twin in total ancestry may actually look more like a white person, and vice versa.

Now let’s go back to first principles. We’ll make some simplifying assumptions to illustrate what’s going on easily. Take 6 genes which control skin color. Assume equal effect. Each gene comes in two variants. Light and dark. Two copies of light result in a value of 0, while two copies of dark result in 2. A copy of each results in 1. In other words, the alleles are additive across a locus. Also assume that the genes are independent. They’re not linked. So the value at each gene is independent of the other genes. Finally, assume that the genes’ implied values summed together result in a total pigmentation phenotype outcome. So they’re additive across loci.

To make even simpler let’s assume that the parents are F1 African-European hybrids. That means that one of their parents’ was European and the other African. So both share the same ancestry of recent vintage. As it happens Africans and Europeans are very different on pigmentation genes, so we can assume that these parents carry one light copy and one dark copy across the six genes. This means you’d expect them to be brown.

Since they are brown, wouldn’t their children be brown? No. Not necessarily. As per Mendel’s Laws each contributes contributes one gene copy at each locus. So for the 6 loci above each parent contributes one pigmentation gene. What does that mean concretely? I Already simplified things to produce an elegant outcome: the F2 offspring could be all light, all dark, or one copy of both, like their parents, at any given gene. To illustrate what I’m talking about, SLC24A5 is disjoint in frequency across Africans and Europeans. All Europeans have one variant, and all Africans have another. So the offspring of a marriage between an African and a European will be heterozygote on that locus. If they marry another person of similar background, homozygote light and dark genotypes will resegregate out at fractions of 25% each, with half the outcome being heterozygote as in the parental condition. In other words, there are a 25% probability of a F2 child of F1 hybrids being “white” at this locus. There are 6 loci. Assuming independent probabilities, you multiply out 0.256, and get 1 out of ~4,000 that the child will be white like their white grandparents.

I ran this as a binomial 10,000 times, and here’s the distribution I came up with:

The white and black offspring don’t show up because the number of outcomes is so rare in this model, but as you can see the median outcome is brown, like the parents. But the tails are significant. In other words, don’t be surprised if there’s a lot of variation among the siblings. But why should you be? If you know of people from populations where pigmentation alleles are segregating in polymorphic frequencies, such as Latin Americans and South Asians, you are aware that different siblings can look strikingly different when it comes to complexion. Though I guess that’s a new insight for the British….

August 31, 2011

Why Melanesians are blonde resolved?

Filed under: Blonde Melanesians,Human Genetics,Human Genomics,Pigmentation — Razib Khan @ 11:08 am
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 [...]

September 28, 2010

To gain pallor is easier than losing it

journal.pbio.0000027.g002

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:


skinvarianceWhat you’re seeing here are patterns of relationships by population when it comes to the select subset of genes which we know are implicated in between population variation in pigmentation. The peoples of Melanesia are arguably the darkest skinned peoples outside of Africa (and perhaps India), and interestingly they are closer to Africans than any other non-African population. But in total genome content they’re more distant from Africans than other non-African populations, excluding the peoples of the New World.

This disjunction between phylogenetic relationships when looking at broad swaths of the genome, as opposed to constraining the analysis to the half a dozen or so genes which specifically encode between population differences on a specific trait, is indicative of selection. In this case, probably functional constraint on the genetic architecture. From the reading I’ve done on skin pigmentation genetics there is an ancestral “consensus sequence” on these genes which result in dark complexions. In contrast, as has been extensively documented over the last few years there are different ways to be light skinned. In fact, the Neandertals which have been sequenced at those loci of interest also turn out to have a different genetic variant than modern humans.

How to explain this? I think here we can go back to our first course in genetics in undergrad: it is easier to lose function than gain function. The best current estimate is that on the order of one million years ago our species lost its fur, and developed dark skin. And it doesn’t look like we’ve reinvented the wheel since that time. All of the peoples termed “black” across the world, from India, to Australasia, to Africa, are dark because of that ancestral genetic innovation. In contrast, deleterious mutations which “break” the function of the genes which gave some of us an ebony complexion occur relatively frequently, and seem to have resulted in lighter skinned groups in more northerly climes. It turns out that some of the pigmentation genes which are implicated in between population variance in complexion were actually originally discovered because of their role in albinism.

So how does this relate to the New World? I think the difficulty in gaining function once it has been lost explains why the people of Peru or the Amazon are not as dark skinned as those of Africa, Melanesia, or South Asia. They haven’t had enough time to regain function which they lost as H. sapiens traversed northern Eurasia. So there you have it. A nice little illustration of how the genetics taught to 18 year olds can be leveraged by the insights of modern genomics and biological anthropology! In the end, nature is one.

Image Credit: Dennis O’Neil

August 18, 2010

Blondes of the ‘black islands’

Populations_first_wawe_migrRecently 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.

Before we go any further, I want to express my skepticism at the idea that this is European admixture. The loci associated with higher odds of having blonde hair in Europeans, OCA2, KITLG, etc., also result in light skin, and secondarily blue eyes. In other words in Europeans blonde hair is to a large extent one effect of generalized depigmentation. There is no magic “blonde gene” which operates independently from the variants which produce lighter skin, or lighter eyes. Though the outcome is not deterministic, the probabilities make it so that someone who has naturally blonde hair is very unlikely to have dark brown skin, at least in any genetic architecture we’re familiar with in Europeans (e.g., African Americans with light eyes and/or hair, also tend to be light skinned).

But if you want more than my logic above, here’s a STRUCTURE plot from The Genetic Structure of Pacific Islanders:

melanesiastruc

I reedited for clarity. Remember that K = putative ancestral populations. So you’re looking for population substructure, and inferred admixture. I’ve compared the Oceanian groups to French from the HGDP sample. The Polynesians in the sample have clear European admixture, but the Melanesians generally do not. The aforementioned Tolai are one of the groups analyzed in this paper, and contrary to one of their explanations for their high frequency of blondness they do not some to have any European ancestry.

What about bleaching? I will be interested to hear what readers have seen, but to my limited knowledge dark skinned populations in other oceanic environments do not seem to have such bleached hair. But, relatively simple forms of hair bleaching do exist which would be possible for a less affluent population to practice as a rite of some sort, or perhaps for simple aesthetic reasons. I put a modest probability on this being the full explanation for this phenotype, and a high probability for it being some of the explanation.

So let’s move to the most novel explanation: that the populations of Oceania have an independent genetic architecture for the emergence of lighter hair color. For me the biggest factor to weight in this hypothesis’ favor is that to my knowledge there are only two population groups in the world which have an appreciable frequency of lighter hair which are not of West Eurasian origin, and they are the indigenous peoples of Melanesia and the Australian desert (this trait seems to be relatively common in the children of the Warlpiri people for example). As we noted last week these two populations form a natural phylogenetic clade, so it seems highly coincidental to me that both exhibit the unique phenotype of relatively dark general pigmentation, but lightness of hair. Additionally, like Europeans lighter hair color seems to be concentrated among children and women in both these groups, aligning with what we know are the correlations of pigmentation and hormones (males and adults are darker).

One obvious model for the blondeness of central desert Australian Aboriginals is European admixture. But the same problems emerge as in the case of the Melanesians: of presumed European traits only the blonde hair expresses, which is a highly peculiar phenomenon. Additionally, we have a relatively recent report from a scientific perspective on the genetics of this trait among these populations, Joseph Birdsell’s Microevolutionary Patterns in Aboriginal Australia: A Gradient Analysis of Clines. The book is from 1993, and no doubt most of the research was done earlier, so the techniques and analyses may seem a bit crude to us. Birdsell observed that the inheritance pattern of blonde hair among the desert Aboriginals exhibited “incomplete dominance.” He recorded that the frequency of the trait was rather high within these tribes, at least for children and women. Additionally, he observes that people with an eastern Aboriginal parent and European parent usually had brown hair of various shades. But among individuals who had one blonde (at least as a child) desert Aboriginal parent and a European parent the offspring tended to be disproportionately blonde, even if the European parent was a brunette! Finally, he observed that aside from head hair, only the body hair of the forearm was blonde. The rest was dark in these Aboriginals.

From what I can tell Birdsell’s monograph is the only recent scientific exploration of this particular topic of blondism among the peoples of Oceania. Many physical anthropologists record the observation of non-black hair among these peoples, but for most their interest did not go beyond cataloging the fact, or it was an incidental result in a bigger project. There’s still a lot about human variation we don’t know. In regards to human pigmentation most of the puzzle has been completed. This is one piece which remains to be found.

Addendum: Some work on the pigmentation genetics of Melanesian populations has been done. They resemble Africans more than any other non-African group in their genetic architecture of loci implicated in the variation of pigmentation. That would basically eliminate the European admixture model to my mind to explain light hair, and increase the probability of bleaching and/or a different and unknown locus.

Note: Blondism among North African, Middle Eastern, Central and South Asian populations is I believe either simply part of the natural continuum of West Eurasians, or, admixture from Europeans or other blonder groups. I believe that this is even the source of blondism among groups like the Hmong, who have a legend of migration from deeper in Asia, where they may have mixed with West Eurasian populations on the fringes of China proper.

Related: Blondism in Melanesia.

* The highest peak in New Guinea is ~14,000 feet above sea level, and in the higher reaches of the uplands it snows periodically.

Image Credit: Wikimedia

Powered by WordPress