Saturday, June 14, 2014

A hair-color allele of Neanderthal origin?


 
Taiwanese aboriginal children, Bunun village (source: Jeremy Kemp). 60-70% of Taiwanese aborigines have a loss-of-function allele at the main hair color gene, MC1R, yet their hair is as black as humans with the original “African” allele. This seems to be a general pattern in Asians. They have fewer MC1R alleles than do Europeans, and the ones they have produce the same hair color.

 

When I first wrote about the puzzle of European hair and eye color, a common explanation was Neanderthal admixture. Modern humans intermixed with Neanderthals in Europe, and one legacy of this intermixture is the high prevalence of non-black hair and non-brown eyes we see in present-day Europeans.

I was skeptical. Scientists had already retrieved mtDNA from the remains of Neanderthals and early modern humans, and there was no discernible genetic continuity between the two. Neanderthal admixture seemed minor and could hardly account for the high proportion of Europeans who deviate from the species norm of black hair and brown eyes (Frost, 2006).

With the sequencing of the Neanderthal genome, it became apparent that some admixture had taken place, but only on the order of 1 to 4% in modern Eurasians. Neanderthals did resemble modern humans in having the same main gene for hair color, i.e., MC1R, but the Neanderthal allele at that gene was unlike any allele in modern humans (Lalueza-Fox et al., 2007). Moreover, there was no evidence of the polymorphism that exists for European hair color. The same allele was present in the two Neanderthal individuals that had been sampled.

That seemed to be the end of the story. A new twist, however, has been added by a recent paper. Ding et al. (2014) have found that one of the MC1R alleles in modern humans (Val92Met) appears to be of Neanderthal origin:

In this paper, we present evidences of Neanderthal introgression encompassing the MSH receptor gene MC1R. Furthermore, our evidences support that the derived allele at the functional variant Val92Met of MC1R (i.e., rs2228479*A) is likely of two origins: the vast majority of haplotypes carrying this allele in the human gene pool is resulted from Neanderthal introgression, while one haplotype (NA19084_a) carrying this allele may be from a recurrent mutation in the AMH linage, double recombination, or biased gene conversion.

This finding is consistent with the theory, first advanced by Gregory Cochran, that archaic admixture made it easier for modern humans to adapt to new environments. To be sure, Val92Met is only one of eleven derived MCIR alleles that exist in modern humans. But Ding et al. (2014) also believe that some of these other MC1R alleles are mosaics of Neanderthal and non-Neanderthal segments. So Neanderthal admixture may have helped European hair color to diversify by providing raw material for selection to act on.
 

A silent allele or a silenced allele?

By itself, Neanderthal admixture cannot explain the unusual diversity of hair color in present-day Europeans. It simply provided some of the raw material for this evolutionary development, and in most cases this raw material had to undergo further changes, through mutation and recombination, before it could become useful.

Indeed, despite being a loss-of-function allele, Val92Met seems to produce the same black hair as the original "African" allele. This may be seen in its geographic distribution: ~5% in Europeans, ~30% in continental East Asians, and 60-70% in Taiwanese aborigines (Ding et al., 2014). It has also been reported in South Asians, Papua-New Guineans, Japanese, and Inuit (Harding et al., 2000). Ding et al. (2014) state that this allele is associated with red hair, but the study they cite found only one individual with Val92Met among the 21 redheads examined (Valverde et al., 1995). This proportion is almost identical to the allele's incidence among Europeans in general. More likely than not, that single individual owed her red hair to an allele somewhere else on her genome.

Hair color is much less diverse in Asians, and this is reflected in lower MC1R diversity. Whereas Europeans have eleven MC1R alleles, Asians have only five, and all five produce the same black hair color (Harding et al., 2000). In short, Asians have fewer alleles and proportionately fewer of these differ phenotypically from the ancestral African allele. It looks as if something downstream prevents these alleles from affecting hair color.

As I've argued elsewhere, Europe's diverse palette of hair and eye colors is due to unusual evolutionary circumstances, i.e., intense sexual selection of women within an ecozone (continental steppe-tundra of the last ice age) where almost all food was obtained through long-distance hunting. The consequently higher death rate and lower polygyny rate among hunters dried up the pool of men available for mating and increased competition by women for mates. Women were more strongly selected for eye-catching traits, particularly bright or novel hues, thus creating an increasingly diverse palette of hair and eye colors (Frost, 2006; Frost, 2014).

This ecozone was more suitable for continuous human settlement in Europe than in northern Asia, where it was farther north and farther removed from the moderating influence of the Atlantic. A site in central Siberia from the last ice age has yielded human DNA that shows strong affinities with present-day Europeans and Amerindians, but much less affinity with present-day northern Asians, who seem to be largely the product of repeopling from the south near the end of the last ice age (Maanasa et al., 2014). Europeans have thus better preserved the legacy of this episode of intense sexual selection.

Perhaps the story ends there. Present-day Asians have preserved less of that MC1R diversity and what they have preserved has less functional significance. Or perhaps that diversity was initially functional and then gradually ceased to be functional … because of some other selection pressure? Perhaps, at the end of the last ice age, there was some non-black hair among northern Asians, though much less than among Europeans. Being less common and thus less normal, and no longer favored by intense sexual selection, there may have been stronger social selection to eliminate deviant hair colors.

A similar kind of social selection might explain why red hair is less common than blond hair among Europeans, i.e., stigmatization of redheads that was ultimately due to a mental association between red hair and menstrual blood (Frost, 2012).

There may be a story behind these "silent alleles." 
 

References 

Ding, Q., Y. Hu, S. Xu, C. Wang, H. Li, R. Zhang, S. Yan, J. Wang, and L. Jin (2014). Neanderthal origin of the haplotypes carrying the functional variant Val92Met in the MC1R in modern humans, Molecular Biology and Evolution, published online June 10, 2014
http://mbe.oxfordjournals.org/content/early/2014/06/02/molbev.msu180.abstract

Frost, P. (2006). European hair and eye color - A case of frequency-dependent sexual selection? Evolution and Human Behavior, 27, 85-103. 

Frost, P. (2012). Why are redheads less common than blondes? Evo and Proud, March 10
http://evoandproud.blogspot.ca/2012/03/why-are-redheads-less-common-than.html  

Frost, P. (2014). The puzzle of European hair, eye, and skin color, Advances in Anthropology, 4, 78-88.
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=46104

Harding, R.M., Healy, E., Ray, A.J., Ellis, N.S., Flanagan, N., Todd, C., Dixon, C., Sajantila, A., Jackson, I.J., Birch-Machin, M.A., and Rees, J.L. (2000). Evidence for variable selective pressures at MC1R. American Journal of Human Genetics, 66, 1351-1361. 

Lalueza-Fox, C., H. Römpler, D. Caramelli, C. Stäubert, G. Catalano, D. Hughes, N. Rohland, E. Pilli, L. Longo, S. Condemi, M. de la Rasilla, J. Fortea, A. Rosas, M. Stoneking, T. Schöneberg, J. Bertranpetit,  and M. Hofreiter. (2007). A melanocortin 1 receptor allele suggests varying pigmentation among Neanderthals, Science, 318 (5855), 1453-1455.
http://www.bio.davidson.edu/courses/genomics/Exams/2009/Neaderthal_pigment.pdf  

Maanasa, R., Skoglund, P., Graf, K.E., Metspalu, M., Albrechtsen, A., Moltke, I., Rasmussen, S., Stafford Jr, T.W., Orlando, L., Metspalu, E., Karmin, M., Tambets, K., Roots, S., Mägi, R., Campos, P.F., Balanovska, E., Balanovsky, O., Khusnutdinova, E., Litvinov, S., Osipova, L.P., Fedorova, S.A., Voevoda, M.I., DeGiorgio, M., Sicheritz-Ponten, T., Brunak, S., Demeshchenko, S., Kivisild, T., Villems, R., Nielsen, R., Jakobsson, M., and Willerslev, E. (2014). Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans. Nature, 505, 87-91.
http://cteg.berkeley.edu/~nielsen/wordpress/wp-content/uploads/2013/12/Raghavan-M.-et-al.-2013..pdf  

Valverde, P., E. Healy, I. Jackson, J.L. Rees, and J. Thody. (2005). Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans, Nature Genetics, 11, 328-330.
http://www.nature.com/ng/journal/v11/n3/abs/ng1195-328.html

21 comments:

Sean said...

"Being less common and thus less normal, and no longer favored by intense sexual selection, there may have been stronger social selection to eliminate deviant hair colors. "

Well maybe, but I bet the selection was against men with red hair, as red hair is somewhat sex linked. And it goes with very pale skin.

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Redheads have thicker hair shafts. Blondes have many fine scalp hairs.

Neanderthal research from earier this year "Neanderthal genes came to dominate certain human traits, including a gene related to keratin, a protein in hair and skin".

Fine, and thus shiny, hair is what women want, so my if there is anything to this, my bet is that red hair came first, and Neanderthal DNA that was lying around unused in the genome came through to influence the more eye catching (and much finer) blonde hair later.

I have my doubts though because these things tend to get over interpreted One of the scientists was on the BBC talking about the supposed Neanderthal link to diabetes and he said only 2 Neanderthal genes out of the over 50 implicated, and what we could be seeing is just the slow purging of Neanderthal genes out of the modern human.
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And those studies are all speculating in terms of light skin being was selected for UVb synthesis of vitamin D (which I know is totally wrong) with red hair being a side effect. But, Neanderthals were FURRY, if they had a brownish coat it would have been for camouflage, like many forest animals that have reddish brown coats.

It would make sense for red hair to go with very light skin if red hair genes came from Neanderthals whose skin was hidden under a coat of fur.
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"In short, Asians have fewer alleles and proportionately fewer of these differ phenotypically from the ancestral African allele. It looks as if something downstream prevents these alleles from affecting hair color."

Or maybe they were never nonsynonymous because the Neanderthal alleles in Asians never got selected for being nonsynonymous alleles that each confer a distinct phenotypic variant. Neanderthal color was likely a type of camouflage pattern controlled in a completely different way from modern human hair, we know they couldn't run prey down, so they had to ambush.

Anonymous said...

It looks as if something downstream prevents these alleles from affecting hair color.

I expect it is simply that Val92Met is not a LOF variant. Or at least, not to a significant degree.

http://jcs.biologists.org/content/115/11/2349.full.pdf - Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation- Human melanocytes homozygous for Arg160Trp, heterozygous for Arg160Trp and Asp294His, or for Arg151Cys and Asp294His substitutions, but not melanocytes homozygous for Val92Met substitution, in the MC1R demonstrated a significantly reduced response to α- melanotropin. "One report (Xu et al., 1996) suggested that the Val92Met substitution reduces the binding affinity of MC1R for α-MSH, while another found no alteration in the functional coupling of the receptor to adenylate cyclase (Koppula et al., 1997). This variant was identified in Chinese individuals, and therefore is not associated with a red hair phenotype (Box et al., 1997).
Here, we showed that NHM 755-c, homozygous for Val92Met substitution, responds dose-dependently to α-MSH with stimulation of cAMP formation, tyrosinase activity and proliferation, suggesting that this polymorphism does not represent a loss-of-function in the MC1R (Fig. 1A-C)."


http://jmg.bmj.com/content/42/7/583/T2.expansion.html - The V60L (Val60Leu) and V92M (Val92Met) are somewhat common mutations, but do not lead to MC1R loss of function

I wonder what the adapative advantage here was though? It's not a rare color advantage or lighter skin tone.

Here's the Alfred frequency data (rs2228479) (rs at snpedia http://www.snpedia.com/index.php/Rs2228479 and given the paper - http://www.academia.edu/7321827/Neanderthal_Origin_of_the_Haplotypes_Carrying_the_Functional_Variant_Val92Met_in_the_MC1R_in_Modern_Humans) http://alfred.med.yale.edu/alfred/SiteTable1A_working.asp?siteuid=SI663688L. No clear regional pattern. Apparently the derived variant at frequency 99% in a Polish sample of 770 subjects. Wtf?

Gottlieb said...

Denisova may not have had any effect on it?

Miscegenation is characterized by uncoupling of the standards previously established between two ancestral races. A person with European predominant phenotype may have more African genetics (for my parents) than someone with mulatto appearance.

The Asians may be more or less like this, if Neanderthals was more fair skin, however, that fossil found in Luxembourg refute the idea that Neanderthals already had clear skin, because it is a relatively new fossil, or an fossil of a individual can not explain the phenotypic variation of all the peoples concerned.
It is as if the ancient Egyptians and modern Indians, two people with several genes that favor for clear skin but without characteristic expression.
An accumulation of genes that predispose to the manifestation of the phenotype. Before it is necessary that all or most have the recessive variations.
If Asians go to select for clear skin, I do not doubt that they will develop many of the attributes that today are abundant in European, especially from the north.

I think all races can select for traits that Europeans, the difference is the phenotypic distance, physical appearance, these compared to Europeans. For Africans turned white, will take thousands of years. To Easterners become much clearer can take less time.

Anonymous said...

"Neanderthals were FURRY, if they had a brownish coat it would have been for camouflage, like many forest animals that have reddish brown coats"

if one wanted to design camouflage for temperate forests, the palette of european hair & eye colours would be imaginable?

***

I'm curious as to why Europeans select sexually but East Asians select socially? You mean because gender ratio was different? It may be of interest that on MacDonald's map (Univ Illinois), Europe is shown to have a predominantly one to one mt to Y hgs ratio. In East Asia, for a wide area, there are the same 4 mt hgs for mainly the one Y hg. meaningful or coincidental?

Sean said...

I expect that alleles from Neanderthals cause instability ("double recombination, or biased gene conversion") when they get into modern humans. So they may be were a source of variability for selection to act on. I very much doubt Neanderthal pigmentation alleles could just be plugged into modern humans and be advantageous. Neanderthals would need countershading not eye catching colours.

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The female Neanderthal hybrids were probably infertile as there is no trace of Neanderthal ancestry on the X chromosome.

Anonymous said...

https://encyclopediadramatica.es/Faintsmile1992

Anonymous said...

Gottlieb don't you post at Anthroscape? Then you should take a look at Faintsmile1992's entry above. Faintsmile1992 new identity is "Bonesanbehaviours".

Gottlieb said...

I've attended the anthroscape few years ago but I was banned. Sefarditaiberico, this was my nickname. I do not intend to discuss in more anthroscape, because the english is not my native language. I need to be prepared to be able to discuss in forums like this.

ben10 said...

" Neanderthals were FURRY"

Perhaps yes, but PROOF?

Were their fur monochromatic or patterned?
Were they bald, or had some colorful features of facial skin pigmentation like the mandrills with purple, red and blue?
Were they very fatty, like a bear, or rather skinny? short or long lifespan?, duration of gestation?, menopaused or not for females, menstruation in winter or not?
There are a thousand more features they could have transmit to moderns humans that modified hair and eyes color alleles.

Genetic is not 100% reliable to answer these questions.

Gottlieb said...

http://www.criadoronline.com.br/boletim/textos/preview_clubes.asp?nr=1308&idc=3

It's in Portuguese, but there is no google translator just for garnish.
Also has the work of Rushton on this topic, but this text shows us that skin color is not a particularity of a race, but is the result of different processes of maturation and temperament selection. Maybe it is not the most important light colored and dark colored, but the variety of coloring, as this text showed.

Anonymous said...

"I'm curious as to why Europeans select sexually but East Asians select socially? You mean because gender ratio was different?"

The idea being presented is based on the form of food getting at the time of selection. Hunters select on human capital i.e. sexual selection. Farmers arrange marriages on the basis of physical capital i.e. land ownership.

So a hunter society with a female surplus due to high male mortality ought to lead to sexual selection on the female.

I think this makes sense generally although whether that is a primary or secondary drive with hair color is debated.

(You'd think the same would be true in the NE Eurasia also even if to a lesser extent however...)

.


"It may be of interest that on MacDonald's map (Univ Illinois), Europe is shown to have a predominantly one to one mt to Y hgs ratio. In East Asia, for a wide area, there are the same 4 mt hgs for mainly the one Y hg. meaningful or coincidental?"

Meaningful imo but maybe in the opposite. To me it hints at east Asian agriculturalists expanding over multiple population groups - presumably forager ones - replacing the males whereas the euro picture is of a single population selecting in place.

.

So I wonder if the underlying difference here between East Asia and Europe is actually much smaller and the actual difference is the farmers in East Asia replaced the foragers much more completely than Europe and were only overwhelmed by the steppe after their population was too large to be impacted (and after the steppe people had changed phenotype also) whereas in Europe the farmers *almost* replaced the foragers but not quite and were then themselves overwhelmed by the steppe while their population was still relatively small (and while the steppe phenotype hadn't changed to the farmer one).

So maybe East Asia had diverse looking northern foragers also at one time but they were replaced by a dramatic expansion of a new farmer phenotype from its source whereas in Europe the dramatic expansion of the farmer phenotype was stalled by an early steppe expansion leading to a lot more surviving forager dna.

maybe

Anonymous said...

As to the MC1R connection has it any relation to the red/copper tone of native Americans and does that red/copper tone effect UVR?

.

Given that pheomelanin is associated with nipple color, lip color etc I wonder if it is associated with sexual selection more generally i.e. firstly minor changes that only effect the color of lips or nipples and then a second more dramatic mutation that effects hair?

Sean said...

Their finger bones and lack of needles show that Neanderthals had fur. Their remains also show they couldn't run fast or throw spears; hence they very likely needed to get the prey running toward the stabbing spears for a killing strike. So they had a camouflage pattern. They are believed to have matured very young. (I personally would not be surprised if it was through Neanderthals captured as infants and kept as pets that Neanderthal genes got into modern human groups).

The Châtelperronian culture is a good bet for the Neanderthal introgression because it was in western Europe, and the ground zero of red hair appears to have been at the western end of the steppe tundra zone.

Anonymous said...

@Anonymous

Understood. Thank you.

Anonymous said...

'Faintsmile1992 new identity is "Bonesandbehaviours".'

Thanks for that. This person is now trying to make a name for themselves among HBDer's and comments on most blogs, however they hide their real identity.

Anonymous said...

The idea being presented is based on the form of food getting at the time of selection. Hunters select on human capital i.e. sexual selection. Farmers arrange marriages on the basis of physical capital i.e. land ownership.

I think Peter has argued that sexual selection operated in African farming societies.

Anonymous said...

"I think Peter has argued that sexual selection operated in African farming societies."

Yeah I'm just speaking to a possible reason for the different end result between East Asians and Europeans i.e. *maybe* East Asia had diverse looking northern foragers also but the East Asian farmer wave more completely replaced them than the Euro farmer wave replaced the euro northern foragers.

The difference in y dna to mtdna ratios might hint at that?

Peter Fros_ said...

Sean, Anon,

I suspect both of you are right. Val92met looks like a synonymous allele (or almost synonymous). The same may be true for the other Asian MC1R alleles. The view that these alleles are functionally different seems to go back to Rosalind Harding, who wanted to minimize the MC1R difference between Europeans and East Asians.

"As to the MC1R connection has it any relation to the red/copper tone of native Americans and does that red/copper tone"

I doubt it. Geographic differences in skin color seem to involve other genes. Amerindians and sub-Saharan Africans have the same ancestral MC1R allele.

"I'm curious as to why Europeans select sexually but East Asians select socially? You mean because gender ratio was different?"

I'm saying that sexual selection of women was unusually strong in a certain kind of environment, i.e., continental steppe tundra. This environment covered much of Europe during the last ice age and also extended across northern Asia as far as Beringia. This environment was colder and drier in northern Asia, however, because it was farther north and farther from the moderating influence of the Atlantic, so it supported a smaller human population and was vulnerable to depopulation, particularly at the height of the last ice age. Genetic evidence indicates that this population did not survive to the present, at least not largely. The current population of northern Asia seems to be largely descended from people who later moved in from the south or from ice age refugia along the Pacific coast.

So the effects of that episode of intense sexual selection have survived to a greater degree at the western end of that Eurasian steppe-tundra belt.

Bruce said...

Peter,
Is there any evidence that the relative hirsuteness of some ethnic groups comes from archaic populations e.g. Neanderthals or Denisovans?

Anonymous said...

Peter Frost This environment was colder and drier in northern Asia, however, because it was farther north and farther from the moderating influence of the Atlantic, so it supported a smaller human population and was vulnerable to depopulation, particularly at the height of the last ice age. Genetic evidence indicates that this population did not survive to the present, at least not largely. The current population of northern Asia seems to be largely descended from people who later moved in from the south or from ice age refugia along the Pacific coast.

Lazaridis et al gives the estimates of Ancient North Eurasian ancestry in populations as

- Karitiana Indians (from Brazil) - 41%
- Chukchi (Arctic people) - 20%
- Ulchi (Russian Far East) - 13%
- Eskimo - 24%

None of these people have especially light hair or eye pigmentation (they're no blondie Soloman Islanders).

And neither do they have particular diversity on the genetic variants implicated in light hair and eyes in Europeans (and to a lesser extent other West Eurasians).

Yet note that the Ancient North Eurasian is highly divergent to the Ancient Western Eurasian ancestry, which has contributed to all Western populations (including to Middle Eastern people to a high degree, over 50%).

Ancient Western Eurasian is the closest relative of Ancient North Eurasian, but not a close relative.

Indeed that's why the Chukchi, adjusted for drift, are scarcely closer to present day West Eurasians than are Han Chinese (but they are a little, adjusted for drift).

So the variants in ANE could be quite different... but we would expect them to be subject to the same evolutionary dynamic under Frost's theory.

Basically, all this is very hard to test.

Anonymous said...

"So the variants in ANE could be quite different... but we would expect them to be subject to the same evolutionary dynamic under Frost's theory."

What percentage of the total genotype is involved in the parts of the phenotype that would be effected?

Changes in the phenotype might make up a significant percentage of the *difference* between two groups but a low percentage of the total.

For example imagine two fighter planes or two tanks from the same era: the best and the second best. They will be c. 95%+ the same but the small percentage of difference between the best and the second best will be the difference between who survives and who doesn't.

#

nb I do think Amerindians are the potential fly in the ointment here

nb In which case I wonder if there may have been an initial random mutation that got the ball rolling in the west that didn't happen in the East

nb Another thought was I wonder if diversity in the visible parts of the phenotype requires recessives and so there's a critical mass needed to keep it going (which might tie in to the idea of the East Asian farmer phenotype expanding more completely in the East than the West Asian farmer phenotype did in the West).