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PLoS Genet 9(11): e1003912. doi:10.1371/journal.pgen.1003912
The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent
Chandana Basu Mallick et al.
Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India.
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36 comments:
From the shape of the contours it looks to me like the allele used to be a bit more common to the east but there has been a wash of presumably other alleles from the east.
How European is this gene if it is just as popular in many Middle easterns. It probably is not the only cause for pale skin in Europeans. Something that may be significant that I noticed. Is that the Near easterns who have this gene at the same rate as Europeans are the same Near easterns who are dominted by west Asian in globe13 and K7b most related to north Euro in globe13 and Atlantic Baltic in K7b and Caucasus in K12b most related to Atlantic Baltic in K12b. North Euro and Atlantic Baltic show basically the same distribution. And so far the dominate group from samples of European hunter gathers from Neolithic and Mesolithic age's. This shows a close relationship with pre Neolithic Europeans(and modern Europeans) with people from the exact areas of the Near east that had the same amount of the light skin allele.
That could be why both Europeans and people from that area of the Near east have so much of the light skin allele. Like I said before I doubt it makes a major effect on skin color. How is this allele passed down. If you have a European or west Asian grandparent will you have this allele. Possible why Some Indians have so much is because Autosomal DNA shows they have a tiny bit of European and a lot of west Asian ancestry. Indo Iranian languages were spread by Europeans from Yamna culture in Russia and Ukraine. Ancient DNA has shown they had a high amount of U5a, U4, and U2e which are typical European hunter gather lineages. One of the most popular Y DNA hg's in India is R1a1a1b2 Z93 which traces back to European R1a1a1b S224.
If this allele is only around 25,000 years old that shows close relationship with Europeans and west Asians in that time. This allele probably dominated Europeans ancestors before they ever arrived in Europe. It definitely can not be used as a age estimate of when Europeans went from west Asian tan to what they are now. The west Asian is highest in the Caucasus were the people are generally pale skinned like Europeans I always thought that might mean they have a lot of European ancestry(which they don't) or they are very related. European paleness is not just skin color it is also hair and eye color. Europeans that have the highest north Euro and Atlantic Baltic which come from pre Neolithic Europe generally have light hair and eyes. Which makes me think Euro paleness overall is from pre Neolithic Europe and originated in Palaeolithic age.
This is great. Another genetic study of regional variation to go with the EDAR370A study. Just keep them coming.
"Not in South India". May be it is important to maintain Tribal leadership, cast identity to protect your place in the society.
With a presence of 80% to 100% in NW India, Pakistan, and Afghanistan, my guess is an origin there. If the date can be shifted to 35 - 32 kya, then it could perhaps be related to the origin and spread of the Gravettian and y-DNA haplogroups P, Q, and R.
22 - 28 kya is a bit of an odd date, since that does not correspond to any known expansion or major migration, unless it occurred and became modal relatively late in the Gravettian in Europe - in which case one would need to postulate a huge wave of back migration some time after LGM through both the middle East and back to S Asia - which does not appear likely, even considering IE expansion.
So the "Caucasian gene" first coalesced 22-28 KYA. About half of the present population on earth has that gene, and that is AFTER two world wars where people with that gene predominantly killed one another off.
I don't understand how that happened if humanity came "out of Africa" even 50,000 years ago (and most think it was further back). Was there a bottleneck event AFTER 22KYA which mostly spared those with the "Caucasian gene"? Do they have the dates wrong on the emergence of this gene? Can someone who understands this stuff better explain the paradox?
Apparently I (as an East African) carry this light skin allele (AA) as well based on 23andMe testing. Yet my skin tone is rather brown and not 'light' at all.
If pale skin is selected for by the need for Vitamin D, then eating oats in the rain (rich carbohydrate diets deplete Vitamin D) will provide part of the answer for its selection in N Europe, regardless of its origin.
"With a presence of 80% to 100% in NW India, Pakistan, and Afghanistan, my guess is an origin there".
Hang on a minute. Not so fast to draw conclusions. The paper specifically says:
"We tested if our sequence data supports the well-documented evidence of positive selection for SLC24A5 in previous studies [4], [13], [20], [21], [29], [30] and whether it provides any additional evidence of selection".
And:
"Hence, these observations confirm that SLC24A5 has been under strong selective pressure in Europeans".
And earlier:
"Populations of South Asia live at lower latitudes than would be expected to require selection for lighter skin color on the basis of improved vitamin D synthesis [8]".
And 'selection' involved is theefore unlikely to have involved South Asia. The allele expanded from wherever it had been selected for. The authors' conclusion is: Europe. However we don't know which specific region in 'Europe'.
"With a presence of 80% to 100% in NW India, Pakistan, and Afghanistan, my guess is an origin there. If the date can be shifted to 35 - 32 kya, then it could perhaps be related to the origin and spread of the Gravettian and y-DNA haplogroups P, Q, and R.
22 - 28 kya is a bit of an odd date, since that does not correspond to any known expansion or major migration, unless it occurred and became modal relatively late in the Gravettian in Europe - in which case one would need to postulate a huge wave of back migration some time after LGM through both the middle East and back to S Asia - which does not appear likely, even considering IE expansion. "
Y DNA R1b1a2a1a L11 in western Europe is only dated to be 5,000-6,000 years old. It is absent in Neolithic western European y DNA samples and R1b first appears in copper age Bell Beaker. Its subclades probably spread mainly in the last 4,000 years with Germanic, Italic, and Celtic languages. R1a1a1b1 Z283 in eastern, central, and northern Europe and R1a1a1b2 Z93 in asia. Also have young ages and spread with Corded ware culture(spoe ancestral language to Balto Slavic) and with Indo Iranian and Tocharian languages in Asia during the bronze age. I have said this maybe 20,000,000,000,000,000 times don't just go off modern distribution it hasn't always been that way. Y DNA R was none existent in the vast majority of Eurasia 6,000ybp especially Europe. There is no signs of a Palaeolithic or even Mesolithic Y DNA R lineage surviving throughout Europe.
I trust the experts that some type of culture they call Grav. existed. But who knows how it is connected with Genetics how many remains of this culture do they have anyways. Life is not so simple. Think about all the Human emotions and events happened in those 1,000's of years their lives and histories were just as complicated as ours. Now ay is it this simple.
"So the "Caucasian gene" first coalesced 22-28 KYA. About half of the present population on earth has that gene, and that is AFTER two world wars where people with that gene predominantly killed one another off.
I don't understand how that happened if humanity came "out of Africa" even 50,000 years ago (and most think it was further back). Was there a bottleneck event AFTER 22KYA which mostly spared those with the "Caucasian gene"? Do they have the dates wrong on the emergence of this gene? Can someone who understands this stuff better explain the paradox?"
This is not a Caucasian gene. There is a such thing as the Caucasian race. Many people get a offended when I say race so usually I say Genetic family. Autosomal and mtDNA has proven this. But even back in the 1800's scientist studied human skulls and other features and came up with the same conclusion. Europeans, Middle easterns, and north Africans are in this race.
This pale skin allele is dominate in Europeans and west Asians. The same west Asians who are dominated by west Asian group in globe13. Which is most related to North Euro which is almost completely exclusive to Europe and is dominate in pre Neolithic samples of European hunter gathers. This shows a close relationship between pre Neolithic Europeans and west Asians. Possibly why today Europeans and west Asians share this pale skin allele.
Everything is debatable. The wave of humans which all non Africans descend from may have come 100,000ybp or 200,000 ybp.
Mark,
There is no paradox. NW South Asians, West Asians, and Europeans are and always have been closely related. The people who settled West Asia and Europe came from NW South Asia - first 45-50 kya (-> Aurignacian in Europe), then ~32 kya (-> Gravettian in Europe). West Asia and Europe remained in contact throughout the Neolithic and Bronze and Iron ages, as did West Asia and NW S Asia. While they have also drifted apart, they are still much more closely related to each other than to other extremes of the globe.
@Mark:
There is another allele that is quiet young and is extremely widespread.
A allele that once was identified as the "non-brown-eyes" allele. (meanwhile quiet a lot of alleles are known that affect eye pigmentation.
Hoewever the age of that allele was estaminated as 5K-15K years old and 90% of the popilation in the northern half of Europe does carry it....
I should add to the above that although Siberian/Beringian male Q populations (perhaps arriving there 37-35 kya by archaeological evidence) evidently got diluted by female NE Asian contributions and (probably with it) the Asian EDAR variant while migrating to the Americas (and much later y-DNA C and N carriers further diluted original Siberians), I still find it more likely that this particular light skin allele only arose slightly later, conforming to the y-DNA R branch and the Gravettian (35-32 kya). That makes it easier to explain the huge frequency gradient between NW and NE Asia, while at the same time, there was continued and contiguous population in S Siberia even through LGM, and of course during that time until modern times bi-directional gene flow.
The fact that many Central and NE Asian populations were not agriculturalists until fairly recently might also contribute (more vitamin D in the diet).
from SNPedia, 85% of the Gujarati population in Houston have this allele. I doubt that the origin of the allele lies in Europe. It must be a very old mutation that has its origin in West Asia.
If the proposed Indo-Aryan "invasion" is the cause, then the frequency of this allele does not correlate with the hypothesis.
What age for the mutations you guys prefer?
The distribution of this allele is almost identical to the distribution of Middle Eastern crops as traditional staple foods, like wheat. To me the fact that the allele doesn't show selection in South India but it does in North India is significant. Historically North India consumes mostly wheat but South India consumes mostly rice. I suspect the selection will have something to do with diet rather than pigmentation.
Selection doesn't require an expansion.
"Selection doesn't require an expansion".
In fact selection usually happens in relatively small isolated populations.
"I doubt that the origin of the allele lies in Europe. It must be a very old mutation that has its origin in West Asia".
I'm afraid Europe is the only place that makes sense for the selection. A northern Eurasia region anyway.
"although Siberian/Beringian male Q populations (perhaps arriving there 37-35 kya by archaeological evidence) evidently got diluted by female NE Asian contributions and (probably with it) the Asian EDAR variant while migrating to the Americas (and much later y-DNA C and N carriers further diluted original Siberians), I still find it more likely that this particular light skin allele only arose slightly later, conforming to the y-DNA R branch and the Gravettian (35-32 kya)".
I'm very much inclined to agree. Especially as the authors discovered that the mutation is virtually absent in Tibeto-Burman, Austro-Asiatic and Dravidian speaking people in South Asia. To me it seems very closely associated with Indo-European-speaking people and preseumably entered South Asia with them. Whenevr that was.
Terry,
You keep equating the very NW tip of the subcontinent (NW India, NW Pakistan, and parts of Afghanistan) with S Asia. You should not. That region has been separated from S Asia during most of the existence of AMHs, due to the severe and much-of-the-time extremely dry climate.
These well-known climatic conditions, BTW, also explain the ANI vs. ASI dichotomy.
Barak,
Absence of evidence is not evidence of absence. According to all archeological records, Siberia has been in contact with Europe from >32,00 ya through LGM until recent times. And now we have y-DNA R in Siberia ~25,000 ya (certainly just a lower estimate, as always).
It looks very much like the Gravettian was y-DNA R dominated, as I have always suggested.
Eurologist,
You say there is no paradox, and you base it on the idea that the population waves came from groups that were already closely related. That may be so, but if the authors of this paper are right about the age of the mutation - 22-28KYA, then someone in those closely related groups first got that mutation about 25KYA, after their cousins and relatives and all other OOA humans have at least a 20 thousand year head start filling up Eurasia.
The people around them may have been kinfolk, but they did not have that mutation, if the date was right.
That one person was so much more successful than their kinfolk and everyone else OOA that today they are half the population. To me that is the paradox. That one individual in the Gravettian shows up and so outcompetes their fellows that even though everyone else had a 1000 generation head start, after another 1000 generations they are even.
Was there a more recent OOA bottleneck? Were OOA populations really small right up unto the Gravettian? I think some other posters here are also confused by what they see here, judging from the comments.
Which population shows the oldest age?
"That one person was so much more successful than their kinfolk and everyone else OOA that today they are half the population. To me that is the paradox. That one individual in the Gravettian shows up and so outcompetes their fellows that even though everyone else had a 1000 generation head start, after another 1000 generations they are even".
I think you're looking at the problem from the wrong direction. The mutation must have happened in an individual but the mutation was selected for in the population it was part of. At some later time that population expanded and carried the mutation far and wide.
"Were OOA populations really small right up unto the Gravettian?"
I think that is a reasonable assumption. The big population expansion is with the Neolithic.
"You keep equating the very NW tip of the subcontinent (NW India, NW Pakistan, and parts of Afghanistan) with S Asia".
I'm fully aware that they are basically separate regions. What I am getting at is that even in the very NW of the subcontinent the environmental conditions necessary for selection of the mutation are unlikely to have existed at any time. A 'severe and much-of-the-time extremely dry climate' is not what we would expect to produce the required selection.
Mark for Summit/Sunnoco
"That one person was so much more successful than their kinfolk and everyone else OOA that today they are half the population. To me that is the paradox. That one individual in the Gravettian shows up and so outcompetes their fellows that even though everyone else had a 1000 generation head start, after another 1000 generations they are even."
This is a rather bad picturing of the spread off an autosomal mutation. It is not like the offspring of that one person overpopulated the offspring of everybody else. The first carrier not necessarily has any bigger genetic contribution in the present population that anybody else of her/his time, except for this one allele of course.
Now about being so much more successful (for the allele): if the carriers of the allele had more of offspring by 0,1% average (compared to the other alleles), it could do the trick in 1000 generations. This is hardly a huge success on the level of one person.
Of course partial isolation between population (by distance for example, linguistic barriers, etc..)slows this down, but sexual selection can make much bigger difference than 0,1% and let's say, 0,5% is still not the category of unbelievable out-competing.
Eurologist
"It looks very much like the Gravettian was y-DNA R dominated, as I have always suggested."
You say this about a culture that spanned a huge area that is unlikely to be homogeneous and this is based on precisely _one_ sample? The case of no R in Mesolithic Europe is much stronger than this at the moment and still not strong enough due to the spotty samples.
I also can't see why the spread of this allele should be connected to any uni-parental marker at all. (It is likely that it was connected some times, but unlikely to do so generally.)
An explanation of my earlier post: of course selection did occur in South Asia. But it was selection for appearance, not environmental survival. Pale skin was considered to represent a higher social class.
"Therefore, the complex patterning of light skin allele in India and its correlation with geography, language, and ancestry component observed in the present study, portrays an interesting interplay between selection and demographic history of the populations. This stands in contrast to Europe where the frequency of the light skin associated allele of SLC24A5 has almost reached to fixation and seems to be attributable solely to natural selection".
Mark,
I agree that there is a problem if one holds on to the 22 - 28 kya date; as I mentioned before, especially the lower range of that interval makes little sense, and the upper limit is marginal (I still prefer 35-32 kya). Note that at 95% confidence interval the range becomes 4,900 to 58,400 years (!) using one method, and 21.7 (+- 10.3)kya using another - so it is just a very rough estimate, further broadened if one relaxes the still uncertain underlying mutation rates. Basically, they are saying it likely happened between 10 - 60 kya, which isn't dating it well, at all.
One should also note that such alleles can be more or less "non-flexible" or "flexible": that is, associated skin pigmentation may either be fairly constant, or highly variable with respect to received UV light. Of course, the latter variant is extremely more useful at northern latitudes, but is also very useful at more southern latitude (where irradiation is still less during the winter, and/or due to climate, people spend less time outdoors).
So, for someone who lives at a more southern location but inherited too much dark (and "non-flexible"-type) skin pigmentation (on other markers) relative to the local winters, this mutation might still be quite beneficial.
Paler skin is usually a cold weather adaptation. Both in East Asia, Europe and in Neanderthals.
Red hair in Neanderthals is a different gene, but perhaps it is the same gene for pale skin. I dont recall seeing a paper excluding this. The archaics were around for a lot longer than Homo sapiens, and had longer to diverge. They were cold weather adapted (Neanderthal anyhow) and had much more time to evolve genes with a competitive advantage. Perhaps different genes in different areas. These could then blend in with the Homo sapiens waves.
Pale skin also crops up occasionally at random in other populations (and I dont mean albinos). I think we are looking at the pale skin alleles cropping up in a cold weather area and flourishing in that area. Clearly the asian variant is East asian. I am not sure the western variant evolved in the west though. Could just as easily be north of the caspian as in Sweden. My gut (and fragments from other studies) says it was closer to the caspian than the Atlantic. These were people who were moving freely along the snowline from east to west. It could have been anywhere in their range.
"Red hair in Neanderthals is a different gene, but perhaps it is the same gene for pale skin. I dont recall seeing a paper excluding this. The archaics were around for a lot longer than Homo sapiens, and had longer to diverge. They were cold weather adapted (Neanderthal anyhow) and had much more time to evolve genes with a competitive advantage. Perhaps different genes in different areas. These could then blend in with the Homo sapiens waves".
I too actually suspect introgression rather than mutation. The same for the EDAR370A mutation. In both cases older populations were certainly around long enough to have developed any necessary mutations.
"Could just as easily be north of the caspian as in Sweden. My gut (and fragments from other studies) says it was closer to the caspian than the Atlantic".
Again I am very much inclined to agree.
Slumbery,
What I meant was the start of the movement that became the Gravettian in Europe and that coincided with a second (non-P, non-Q) movement East along S Siberia towards the Altai. I agree, of course we have to await further ancient DNA results to see (i) which subgroups of R where involved, and (ii) how far did they spread, and at what time. Sorry, I was sloppy in my wording.
Annie,
Cold weather, of course, due to covering most of the body - but also latitude (due to solar irradiance variation, which also promotes the "flexible" type allele I talked about above), and even prevalence of cloudy/ foggy weather (e.g., Ireland and Scotland, parts of which have since the Younger Dryas been much, much milder than E Europe or even C Europe during the winter) - see also below.
Terry,
Even today, parts of Kashmir, N Pakistan, and Afghanistan are extremely cold in the winter - of course even more so 30,000 ya. So, while the irradiance factor is surprisingly large there (basically, Mediterranean in winter, but C to N European in the spring, in the wetter regions (!) http://earthobservatory.nasa.gov/IOTD/view.php?id=1355), clothing and staying "indoors" also mean very little received sunlight during a good portion of the year.
The April image also emphasizes my point that this particular region is climatically very insular.
"Even today, parts of Kashmir, N Pakistan, and Afghanistan are extremely cold in the winter"
But you do admit, 'but also latitude ... and even prevalence of cloudy/ foggy weather' is as important. As far as radiation goes latitude is the most important factor.
"while the irradiance factor is surprisingly large there"
So would not lead to selection for white skin.
a couple of very relevant comments from the original paper:
"A significant correlation between skin color and ultraviolet radiation (UVR) levels observed at the global scale suggests that natural selection plays an important role in determining the distribution of this phenotypic trait [8]".
So 'radiation' is accepted as being the main driving force of the selection.
"The ancestral (G) allele of the SNP predominates in African and East Asian populations (93–100%), whereas the derived (A) allele is almost fixed in Europe (98.7–100%)"
And:
"Genome-wide scans have also identified SLC24A5 as one of the most important “hot spots” for positive selection in Europeans, thereby supporting the role of natural selection acting on this gene [4], [20], [21]".
I presume that is the basis on which the authors conclude the SNP was extremely selected for in Europe and not further south. And further:
"Populations of South Asia live at lower latitudes than would be expected to require selection for lighter skin color on the basis of improved vitamin D synthesis [8]".
That would also apply to Kashmir, N Pakistan, and Afghanistan.
Terry,
Did you even take a look at the link I posted? The point was that surface irradiance is highly variable and not just determined by latitude.
"Did you even take a look at the link I posted?"
Yes.
"The point was that surface irradiance is highly variable and not just determined by latitude".
In fact determined by altitude as well. But you even admitted:
"So, while the irradiance factor is surprisingly large there"
So if the selection was for lack of solar radiation it would not have happened in the region you propose. And I have already covered that idea:
"while the irradiance factor is surprisingly large there"
So would not lead to selection for white skin. Cold alone is very unlikely to have led to the required selection although you do have a point with regard to the influence of clothing. But clothing would be an even greater factor in the limited winter radiation levels further north.
Which population shows the oldest age?
"So, while the irradiance factor is surprisingly large there"
Terry,
what I quite obviously meant by that is that the factor in selecting light pigmentation was large, there - in accordance with the link I posted - not that irradiance is/ was large, there.
"I quite obviously meant by that is that the factor in selecting light pigmentation was large"
It wasn't at all obvious, sorry. In fact the higher altitude usually increases the amount of solar radiation making the requirement for the gene's development less likely, not more likely. The post on the Mal'ta boy shows he was dark-skinned. Almost certainly his deeper ancestry goes back to NW India, Pakistan, and Afghanistan and yet he obviously did not carry the SLC24A5 gene. Granted at '22–28 KYA' it may have developed after the boy's ancestors had passed by. But, equally likely, the gene did not originate in the region you propose. Certainly the authors don't think so.
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