Scandinavian hunter-gatherers had double west-east origins

SHG origins' mystery solved? What about possible Norwegian "EHG-like" genetic influences into Atlantic Europe?

Torsten Günther, Helena Malmström, Emma Svensson, Ayça Omrak et al. Genomics of Mesolithic Scandinavia reveal colonization routes and high-latitude adaptation. bioRXiv 2017 (pre-pub). DOI:10.1101/164400

Scandinavia was one of the last geographic areas in Europe to become habitable for humans after the last glaciation. However, the origin(s) of the first colonizers and their migration routes remain unclear. We sequenced the genomes, up to 57x coverage, of seven hunter-gatherers excavated across Scandinavia and dated to 9,500-6,000 years before present. Surprisingly, among the Scandinavian Mesolithic individuals, the genetic data display an east-west genetic gradient that opposes the pattern seen in other parts of Mesolithic Europe. This result suggests that Scandinavia was initially colonized following two different routes: one from the south, the other from the northeast. The latter followed the ice-free Norwegian north Atlantic coast, along which novel and advanced pressure-blade stone-tool techniques may have spread. These two groups met and mixed in Scandinavia, creating a genetically diverse population, which shows patterns of genetic adaptation to high latitude environments. These adaptations include high frequencies of low pigmentation variants and a gene-region associated with physical performance, which shows strong continuity into modern-day northern Europeans.

Fig. 1:

Mesolithic samples and their genetic affinities – (A) Map of the Mesolithic European samples used in this study. The pie charts show the model-based [16,17] estimates of genetic ancestry for each SHG individual. The map also displays the ice sheet covering Scandinavia 10,000 BP (most credible (solid line) and maximum extend (dashed line) following [10]). Newly sequenced sites are shown in bold and italics, SF11 is excluded from this map due to its low coverage (0.1x). Additional European EHG and WHG individuals used in this study derive from sites outside this map (...)

Intriguingly, Swedish Epipaleolithic peoples (SHG) have the light skin variant in the gene SLC45A2, variant that is now uniformly spread through all Europe and accounts for 15% of the skin color variance in a key Cape Verde study and that was so far attributed solely (or almost solely) to Neolithic farmers (among which it was fixated and who had indeed a very large genetic impact in the European subcontinent). They also have the blue eyes allele, as Western Hunter-Gatherers did. However, if we are to follow, Günther's explanations in this video, the variance of looks in Epipaleolithic Scandinavia was greater than in present day. 

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PS- Legend says that when my namesake Fray Luis de León returned to his classroom after five years imprisoned by the Inquisition, he began his class with these words: "As we were saying yesterday..."

Expect less lengthy articles because I really want to use this blog as open notebook, and not spend so much time following news and dissecting them thoroughly, so my style may become a bit more telegraphic. 

I also don't know for how long I will be able to continue blogging, as my personal economic situation is bad and worsening and you never know when police may come and arrest you for saying "fuck the king" or whatever other quite reasonable opinion. We live very troubled times and I'm personally quite bad at winning.

Also my apologies in advance if I fail to quickly approve comments. I usually check my email once per day or so but sometimes I just forget. Please, be patient if that happens: I only censor fascism, racism, sexism and homophobia (and those individuals who have managed to really get on my nerves, and they know who they are). Sadly I have to keep pre-moderating all comments, else the lonely troll will get away with his abuses.

A genetic actor for blond hair in Eurasia

Interesting find on hair color genetic determination, which must be understood nonetheless as only one factor among several in this aspect.

Catherine A. Guenther et al., A molecular basis for classic blond hair color in Europeans. Nature Genetics 2014. Pay per view → LINK [doi:10.1038/ng.2991]

Abstract

Hair color differences are among the most obvious examples of phenotypic variation in humans. Although genome-wide association studies (GWAS) have implicated multiple loci in human pigment variation, the causative base-pair changes are still largely unknown1. Here we dissect a regulatory region of the KITLG gene (encoding KIT ligand) that is significantly associated with common blond hair color in northern Europeans2. Functional tests demonstrate that the region contains a regulatory enhancer that drives expression in developing hair follicles. This enhancer contains a common SNP (rs12821256) that alters a binding site for the lymphoid enhancer-binding factor 1 (LEF1) transcription factor, reducing LEF1 responsiveness and enhancer activity in cultured human keratinocytes. Mice carrying ancestral or derived variants of the human KITLG enhancer exhibit significant differences in hair pigmentation, confirming that altered regulation of an essential growth factor contributes to the classic blond hair phenotype found in northern Europeans.

The study, quite technical, is mostly about mice (a close relative of primates and hence humans) in which a SNP in the same non-coding upstream position relative to the Kitl gene (equivalent to the human KITLG) causes white hair coloration. In the case of some humans it seems to work almost exactly the same way, causing blond coloration of hair, a change already apparent in the mouse embryos.

Figure 1: A distant regulatory region upstream of the KITLG gene controls hair pigmentation in humans and mice.
(b) Frequency distribution of rs12821256 in different populations. The G allele associated with blond hair (yellow) is most prevalent in northern Europe. Green color represents the frequency of the ancestral A allele.

The distribution of the rs12821256-G allele is consistent with the presence of blond hair, including a small slice in SE Asia, where blond hair is known to happen even if rarely. 

However looking particularly at West Eurasia there is still a lot of unexplained blond hair: this allele is most common in England, which is not such an outstanding region for blond hair pigmentation, with highest phenotype frequencies concentrated around the Baltic instead. Basque blondes (which are quite a few) are absolutely unexplained by this particular allele, for example. 

So there must be necessarily other SNPs involved in blond hair formation. One of them was discovered in 2012 among Australasians but it is not found in the mainland apparently. The rest are still unknown.

Central European farmers, but also Danish "hunter-gatherers" had domestic pigs

It's often difficult to discern in the archaeological record wild boar remains from those of domestic pigs. Luckily archaeogenetics can solve the problem, sometimes producing striking results.

Ben Krause-Kyora et al., Use of domesticated pigs by Mesolithic hunter-gatherers in northwestern Europe. Nature Communications 2013. Open access → LINK [doi:10.1038/ncomms3348]

Abstract

Mesolithic populations throughout Europe used diverse resource exploitation strategies that focused heavily on collecting and hunting wild prey. Between 5500 and 4200 cal BC, agriculturalists migrated into northwestern Europe bringing a suite of Neolithic technologies including domesticated animals. Here we investigate to what extent Mesolithic Ertebølle communities in northern Germany had access to domestic pigs, possibly through contact with neighbouring Neolithic agricultural groups. We employ a multidisciplinary approach, applying sequencing of ancient mitochondrial and nuclear DNA (coat colour-coding gene MC1R) as well as traditional and geometric morphometric (molar size and shape) analyses in Sus specimens from 17 Neolithic and Ertebølle sites. Our data from 63 ancient pig specimens show that Ertebølle hunter-gatherers acquired domestic pigs of varying size and coat colour that had both Near Eastern and European mitochondrial DNA ancestry. Our results also reveal that domestic pigs were present in the region ~500 years earlier than previously demonstrated.

The most striking result is surely not the demonstration of pigs being in Central Europe a few centuries than previously confirmed but that Ertebølle hunter-gatherers of Denmark had them as well, quite radically casting doubt on their status as hunter-gatherers and placing them fully in the Neolithic context, even still rather marginal and peripheral. 

Figure 1: Map depicting the location of the archaeological Sus samples from which mtDNA haplotypes were obtained.
Samples were recovered from Neolithic LBK, post-LBK and Mesolithic Ertebølle sites dated between 5500 and 4000 cal BC. Each symbol corresponds to a single sample (triangle, square and circle). Domestic (triangle) and wild (square) pigs discussed in the text are labelled; circles represent Sus specimens of unknown domestication status. The red colour indicates the European haplotypes C and A, and yellow the Near Eastern haplotypes Y1 and Y2.

HERC2 haplotypes worldwide study at Kurdish DNA

I must congratulate again Palisto of Kurdish DNA blog for his excellent work on the description of HERC2 haplotypes and their frequency across world populations. It is not a peer-reviewed academic paper but it could well be, and within the high quality sector.

Palisto, The color of the eyes: at least 17 HERC2 variants in Human gene pool. Kurdish DNA 2013. Freely accessible blog article → LINK

After initially detecting seven haplotypes in the Kurdish genetic pool (which were named ht1-7) and then studying these in the Eurasian gene pool, he decided to study the African haplotypes, largely in the "other" category, as well as comparing them all with the known Neanderthal and Denisovan sequences, at the very least to infer a root. The main result is this tree:

So the ancestral haplotype is ht13, found not just among Neanderthals and Denisovans, but also among scattered populations of H. sapiens both in Africa as in Eurasia-plus. 

From it hang ht8 (Homo sapiens, found in and outside Africa) and ht18 (Neanderthal-exclusive).

This main branch has two major sub-haplogroups, which I will label D and E for convenience (A would be ht13, B ht8, and C Neanderthal-only ht18). Haplogroup D (hts 11, 16 and 17) seems to have remained in Africa (only ht 11 was detected at low frequencies in Lebanon), while haplogroup E (all the rest) massively participated in the migration out of Africa (OoA).

However it must have done already in highly diversified form, as most named haplotypes are found at significant frequencies both outside and inside Africa. There are four exceptions only:

1. Ht9 is only found in Africa (with a minor Arabian exception), so this haplotype did not took part in the OoA.
2. Ht15 has not been found in Africa instead, so it is possible that it evolved already in Eurasia.
3. Ht2 and its descendant ht1 (both of which cause blue eyes, albeit in recessive manner) don't seem to exist in Africa either (with the exception of the HGDP San sample, which seems notably admixed with Europeans, at levels of almost 20%, not your typical Bushmen really), so again they probably arose already in Eurasia. 

These are the wider regional frequencies:

However at the original article there is a much more detailed list, which is probably more interesting to use when pondering each haplotype. For example the overall data for America is pretty much irrelevant, as it groups native peoples with mixed creole ones.

For example we can see that "blue eyes" ancestral haplotype ht2 looks like originated in West Asia, and it may also be the case of its descendant ht1. 

Ht 15 in turn may well have coalesced in Altai, from where it spread to mostly Native American peoples (represented by Mestizo Colombians). A similar pattern can be seen in ht14, however this must be original from Africa (the Biaka have it, as do Mozabites) and therefore it is found also in some other scattered populations like Cambodians, Sindhi, etc.

Something I wonder about is the low diversity displayed by East Asians in this haplotype. Or inversely, why did West Eurasians evolve so all non-African novel variants? While there is still some left to analyze in the ND box, it is very small in East Asia. I wonder if it has some relation with skin pigmentation pathways indirectly influencing this change somehow.

HERC2 haplotypes, phylogeny and frequencies

Palisto at Kurdish DNA has a most interesting report of his own production on the eye color gene HERC2, its variant haplotypes, their phylogeny and their frequency in West Eurasian and Pakistani populations.

Based on Kurdish haplotypes, he developed the following phylogeny:

 

All branches produce dark eye color, excepted the two colored in blue, which are associated with light eye color. 

The defining transitions from branch#3 to branch#1 are rs1129038 and rs12913832 (demonstrated to cause blue eyes in 99% of cases) while the transition to branch#2 is found at rs11636232. 

He also produced haplotype frequency tables for the two light eye color haplotypes (here the one sorted by branch#1 frequencies):

	Branch#1	Branch#2
Brahui	2%	2%
Balochi	8%	2%
Balochi	12%	6%
Kalash	12%	16%
Sardinian	16%	4%
Palestinian	18%	3%
Burusho	18%	12%
Basque	19%	21%
Italians	25%	19%
Adygei	26%	6%
Orcadian	28%	41%
Galician	30%	17%
French	32%	30%
Russians	36%	46%
Italians	42%	27%
Swedes	42%	54%
Germans	46%	33%
Danes	52%	32%
Austrian	55%	28%
Swiss	69%	25%

In West Asia and Pakistan (the most plausible ancient origin of the trait), we see how the ancestral #1 variant is generally dominant, with the only exception of the Kalash, reaching the highest frequencies (18%) among the Burusho and Palestinians, among the studied populations. 

This pattern is continued (at overall quite higher frequencies) in Central Europe, Denmark, Italy and Galicia, with peak among the Swiss (69%). Instead the derived haplotype #2 seems dominant among Swedes, Russians and Orcadians. French and Basques are balanced for both types.


Update (Jun 25): map:

Includes also Kurdish data from Palisto's update.

The two Balochi samples are pooled in one (same weight for each), instead the two Italian samples were retained separated and assumed to be from South and North Italy respectively (not sure but makes sense). 



See also:

• Eye and skin pigmentation genetics: Cape Verdeans as informative population
• Causes of skin and hair color variance in Europeans remain undetermined (includes data for eye color)

Update (Jun 27): Kurdish DNA just published the HERC2 data a much wider sample of populations from all Eurasia and not anymore focusing only on the blue eye haplotypes but all them instead.

It is very interesting that ht3, ancestral to blue eyes' haplotypes ht1 and, through this one, also ht2 , is widespread through the continent with very few exceptions: Russians, Belorussians, Lithuanians and a Mordvin tribe in Europe, as well as the Kurmi, Nihali, Chenchu and Puliyar in India.

Ht5 and ht6 are also very common in Eurasia, ht7 is rare in most groups but dominant in a few (Kurmi, Melanesians) while ht4 (ancestral to ht3) is rather rare as well (highest in South and Central Asia, as well as Lebanon). Other (undetermined) haplotypes are also concentrated in some populations like the Chenchu and have some importance across Asia.

Eye and skin pigmentation genetics: Cape Verdeans as informative population

Cape Verde from space

Still getting updated with the backlog. Here there is an interesting study on human pigmentation using the heavily admixed Cape Verdean (essentially West African + West Iberian) population as reference.

Sandra Beleza et al., Genetic Architecture of Skin and Eye Color in an African-European Admixed Population. PLoS Genetics 2013. Open access → LINK [doi:10.1371/journal.pgen.1003372]

Abstract

Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10−62, SLC24A5 P = 9.6×10−9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10−27, TYR P = 1.1×10−9, APBA2[OCA2] P = 1.5×10−8, SLC45A2 P = 6×10−9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

Children of Praia
(CC by Otimarte)

Most interestingly maybe the authors conclude that KITLG, a gene which displays large differences in allele frequency between Africa and Eurasia and has been therefore suggested to be a cause of pigmentation differences, does not actually play any obvious role in this matter.

HERC2 (OCA2) is confirmed to be very important in eye color (semi-recessive inheritance for blue color), the only other gene known to affect eye color is SLC24A5, which is mostly involved in skin pigmentation however.  

SLC24A5 and SLC45A2 are confirmed as important pigmentation genes. However two otherwise unsuspecting genes, APBA2 (near OCA2) and GRM5-TYR, are found to have also important impact in skin pigmentation.

Still most (~3/5) of the inherited pigmentation traits remain unexplained and are probably caused by some sort of complex interactions. Eye and skin pigmentation have no strong genetic correlation apparently.

Some interesting images from the paper:

Figure 1. Relationship of geography and ancestry to skin and eye color.
Individual ancestry proportions for Cape Verdeans displayed on all four panels were obtained from a supervised analysis in frappe with K = 2 and HapMap's CEU and YRI fixed as European and African parental populations. (a) Bar plots of individual ancestry proportions for Cape Verdeans across the islands. The width of the plots is proportional to sample size (Santiago, n = 172; Fogo, n = 129; NW cluster, n = 192; Boa Vista, n = 27). The proportion of African vs. European ancestry of the individuals is indicated by the proportion of blue vs. red color in each plot. (b) Individual African ancestry distribution in the total cohort of 685 Cape Verdeans (histogram) and in 802 African Americans (kernel density curve) from the Family Blood Pressure Program (FBPP) [21]. (c) Scatter-plot of skin color vs. Individual African ancestry proportions. Skin color is measured by the MM index described in Material and Methods. (d) Scatter-plot of eye color vs. Individual African ancestry proportions. Eye color is measured by the T-index, described in Figure 2 and Material and Methods. Points in scatter-plots are color coded according to the island of origin of the individuals.

Figure 3. GWAS results for skin and eye color in the total Cape Verdean cohort.
Results are shown as −log₁₀(P value) for the genotyped SNPs. Plots are ordered by chromosomal position. (a,c) Genotype and admixture association scan results for skin color. (b,d) Genotype and admixture association scan results for eye color. (a,b) show the P values obtained in the initial scans and (c,d) the P values of the following scans adjusting for the strongest associated SNP (in SLC24A5 for skin color and in HERC2 for eye color). Dashed red lines correspond to the genome-wide significance threshold (P<5×10⁻⁸ in the genotype scan; P<7×10⁻⁶ in the ancestry scan [see Material and Methods]). The location and identity of candidate genes are colored to correspond with chromosomal location; individual SNPs are given in Table 1.

Figure 7. Genetic architecture of skin color variation.

(a) Effect sizes of the loci associated with skin color. Effect values represent the beta values obtained from a regression model containing the four associated loci plus ancestry. (b) The pie chart represents the proportion of phenotypic variation accounted for by the different components, including non-heritable factors (~20%), the four major loci (~35%, color-coded as in [a]), and average genomic ancestry (44%). The heritable contributions were estimated by regression and variance decomposition as described in Material and Methods, and are also represented below the pie chart separately as grey (genomic ancestry) or open (four major loci) areas. However, because of admixture stratification, the heritable contributions overlap as described in the text.

Eye color, face shape and perception of trustworthiness

An old popular Galician song said:

Ollos verdes son traidores...
azules son mentireiros,
os negros e acastañados son firmes e verdadeiros.

Translated:

Green eyes are treacherous...
blue ones are deceitful,
the black and brown ones are loyal and truthful.

Just word of a silly mariner song? Intriguingly science confirms now, in a way, part of this perception (at least for blue and brown eyes).

But notice please that it is the precisely the perception what is being confirmed: people seem to perceive blue eyes in general as somewhat less trustworthy. The study says nothing about people with blue eyes being untrustworthy in fact, just that we tend to distrust them more than people with brown eyes.

Karel Kleisner et al., Trustworthy-Looking Face Meets Brown Eyes. PLoS ONE 2013. Open access → LINK [doi:10.1371/journal.pone.0053285]

Abstract

We tested whether eye color influences perception of trustworthiness. Facial photographs of 40 female and 40 male students were rated for perceived trustworthiness. Eye color had a significant effect, the brown-eyed faces being perceived as more trustworthy than the blue-eyed ones. Geometric morphometrics, however, revealed significant correlations between eye color and face shape. Thus, face shape likewise had a significant effect on perceived trustworthiness but only for male faces, the effect for female faces not being significant. To determine whether perception of trustworthiness was being influenced primarily by eye color or by face shape, we recolored the eyes on the same male facial photos and repeated the test procedure. Eye color now had no effect on perceived trustworthiness. We concluded that although the brown-eyed faces were perceived as more trustworthy than the blue-eyed ones, it was not brown eye color per se that caused the stronger perception of trustworthiness but rather the facial features associated with brown eyes.

So the authors conclude that it is not eye color but associated face shape what drives untrustworthiness because the phenotype associated with blue eyes is more angular, less rounded, at least for males:

Figure 2. Shape changes associated with eye color and perceived trustworthiness.
Thin-plate spline visualizations of the way face shape correlates with eye color (a–f) and trustworthiness (g–i). Generated face shapes of blue-eyed woman (a) and brown-eyed woman (c) compared to average female face (b). Generated face shapes of blue-eyed man (d) and brown-eyed man (f) compared to average male face (e). Generated face shapes of untrustworthy-looking man (g) and trustworthy-looking (i) man compared to average male face (h). The TPS grids of perceived trustworthiness for women are not shown because shape analysis did not meet statistical significance. The generated facial images (a–f) were magnified 3x for better readability.

They claim that they found no correlation with facial shape for women but I find in the image above almost exactly the same pattern for men and women and not only what they detected: notably the blue eyed people (both genders) and the less trusted men all have in my opinion:

• Smaller eyes
• More serious (defiant, analytic, unsympathetic) expression
• Proportionally broader face or at least jaws

In general the faces to the left look significantly colder, less empathic, a perception that blue eyes can only enhance.

The authors ponder if there is a phenotype linkage disequilibrium associating face and eye color, what seems plausible. But then go on speculating about sexual selection and what not. 

In this sense Razib has an interesting critical analysis questioning if selection is behind the blue eye incomplete sweep in West Eurasia or Europe. If I understand him correctly he seems to suggest, never clearly naming it, that blue eye may have been favored because of the associated skin pigmentation trait, a key adaptive value in the dark winters of Europe and very especially the northern half of it.


Update: is this a peculiarity of Central Europe or the Czech Republic?

A reader sent me an email in which it was questioned if this association is peculiar of the Czech Republic, where the study was performed, and can't be extended for example to Britain. Examples of soft-faced blue-eyed Britons mentioned were Hugh Grant and Alec Baldwin (I'm not sure if Baldwin is such a good counter-example but Grant is for sure one such case). 

I find it a very good criticism and hope that entices debate.



See also: Causes of skin and hair color variance in Europeans remain undetermined.

Causes of skin and hair color variance in Europeans remain undetermined

Portuguese & N. Irish

Our ability to predict pigmentation traits from genetic loci remains limited but this new paper adds some honest research on the matter:

Sophie I. Candille et al., Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations. PLoS ONE, 2012. Open access ··> LINK [doi:10.1371/journal.pone.0048294]

One of the findings is that women have darker skin shades than men in Europe (but not among peoples with dark skin from several continents, where men are darker). Another unstated but curiously counterintuitive finding is that Portuguese (from Porto) have on average the same skin tone as Polish (from Warsaw) do:

Table 1. Skin, hair, and eye pigmentation by sex and country.

However for hair and eye color, Polish have lighter shades, approaching the Irish (Dublin) extreme values, while Portuguese approach Italians (Rome) in hair color and show darker eyes on average than anybody else among the sampled populations.

Another curiosity of the survey is that Irish women show significantly lighter hair shades than Irish men, a phenomenon not appreciable elsewhere.

The authors found that, in general:

... in this European sample, pigmentation phenotypes are mainly stratified by country, whereas height is mainly stratified by sex.

They also found that:

Skin and eye pigmentation are correlated in Ireland. Hair and eye pigmentation are correlated in Portugal. Skin and hair pigmentation are correlated in Poland and Italy (Table S2).

What I find rather curious and suggestive of complex genetic influences affecting more than just one pigmentation trait at the same time. But which ones? And why do they seem to operate differently in different populations?

The GWAS analysis found these loci as significant:

Table 2. GWAS, replication, and combined association results for all signals with p-value<10⁻⁵ in the GWAS.

Apparently neither the SCIN nor the FLNB genes have been related with pigmentation before. Therefore the authors applied a strong test of reliability (replication in the table), correcting for geographical structure, which actually discarded all loci except the already known ones for eye color in relation to OCA2/HERC2, which were: rs1667394, rs8039195, rs1635168, rs16950987, and rs8028689.

However further analysis showed that rs1667394 is in linkage disequilibrium (LD) with rs12913832 (OCA2), which is the actual culprit of blue eyes (a well known SNP that explains some 45% of the eye color variance among Dutch).

In regard to the failure to detect markers of skin and hair color variance, they conclude that:

The fact that we did not detect reproducible associations with skin or hair color suggests that, unlike eye color, skin and hair pigmentation variation in Europe are not determined by major loci.

Furthermore, genes that have been shown to contribute to skin color variance in South Asians (rs1426654 SLC24A5, rs16891982 SLC45A2, and rs1042602 TYR) or in African-European admixed populations (rs1426654 in SLC24A5 again), fail to show any importance in intra-European variance for this trait. However rs1426654 is fixated in Northern Europeans (CEU), so it cannot show any variation.

Other SNPs (rs16891982 and r183671 in SLC45A2, which are in LD) may contribute to skin pigmentation, however the pattern mentioned (in which Italians and Portuguese are contrasted with Polish and Irish) rather reminds me of the variation for hair and eye color instead.

They also mention that rs885479 in MC1R has not provided any clear association in previous studies but that they did find some association with skin color, however they did not practice the replication test for this SNP.

In the end not much new other than some cold water but an straightforward study for the record.

See also:

• Predicting pigmentation phenotypes with genetic information (at Yan Klimentidis blog)
• Some population structured SNPs and also one epigenetic factor
• Category "Pigmentation"
• The height of Europeans and the myth of the North-South cline

Blond hair in Melanesia genetically distinct from that of Europeans

Anthropology.net calls my attention today to this paper:

Eimear E. Kenny et al., Melanesian Blond Hair Is Caused by an Amino Acid Change in TYRP1. Science 2012. Pay per view. 

Abstract
Naturally blond hair is rare in humans and found almost exclusively in Europe and Oceania. Here, we identify an arginine-to-cysteine change at a highly conserved residue in tyrosinase-related protein 1 (TYRP1) as a major determinant of blond hair in Solomon Islanders. This missense mutation is predicted to affect catalytic activity of TYRP1 and causes blond hair through a recessive mode of inheritance. The mutation is at a frequency of 26% in the Solomon Islands, is absent outside of Oceania, represents a strong common genetic effect on a complex human phenotype, and highlights the importance of examining genetic associations worldwide. 

Actually natural blond hair is also found in West and Central Asia and North Africa, and red hair even in the Horn of Africa now and then. But I guess that's what the authors mean by "Europe", duh! It's also found occasionally among South Asians, specially the young, and among SE Asians regardless of age.

Whatever the case with the authors ethno-geographic misconceptions, the results are still most interesting: the gene causing blond hair among Melanesians (and some relatives like Fijians) is not the same as those involved in blond hair in Europe. Mind you that it is not clear yet which are these European genes of blondism but it is clear that the Melanesian allele is not it either. 

There is also an article at New Scientist.

Brown eyed Neanderthals of Croatia

Since years ago, when one Neanderthal individual from Gibraltar was identified as having reddish hair color (but not via the Homo sapiens alleles but a different one of their own), some authors have idealized Neanderthals as hyper-white. For example the Gibraltar kid whose reconstruction is pictured at the right, whose skin looks unhealthily way too pale to be living in Andalusia (the Ice Age would not affect solar radiation in principle, only temperature).

Now other researchers have inferred that the Neanderthals from Vindija cave (Croatia) probably had brown eyes, hair and even skin, which is described as tawny, a light brown/orange shade.

Caio C. Cerqueira et al., Predicting homo pigmentation phenotype through genomic data: From neanderthal to James Watson. American Journal of Human Biology 2012. Pay per view. 

The paper is widely discussed at a free article in Science magazine, titled: Were some Neanderthals blue eyed girls?, where the likes of Lalueza-Fox and John Hawks ponder the conclusions, rather critically. 

Of course, the conclusions are far from straightforward:

One complication is that traits such as hair color are controlled by multiple genes. To determine the cumulative impact of multiple genes on one trait, the authors assumed they could simply add together the impact of individual genes. The female Neandertal known as Vi33.26, for example, had seven genes for brown eyes, one for "not-brown" eyes, three for blue eyes, and four for "not-blue eyes." By the researchers' reckoning, that means a six-gene balance in favor of brown and a negative balance for blue, so Vi33.26's eyes were probably brown. According to this method, all three Neandertals had a dark complexion and brown eyes, and although one was red-haired, two sported brown locks. 

They may well be right in regards to the eyes, although we really know way too little on human pigmentation as of now, never mind Neanderthal peculiarities, to be certain at all. In any case, considering that modern Europeans also display variety of eye and hair colors, I see no reason not to imagine that Neanderthals also had dark eyes and hair.

Those traits are after all non-adaptive or mostly so. Instead skin color is key for survival. So I am reluctant to accept tawny as a valid answer for skin color, at least in most of the shades suggested. Very few people if any have tawny skin color today at 45 degrees North, roughly the latitude of Vindija. And that is because of an adaptive reason: the human need to synthesize normally vitamin D using solar energy at the skin (it can also be ingested from fish mostly but it's not as reliable in the long run).

Surely Neanderthals were also biological conditioned in that same way. Although now that I think of it I have never seen a paper stating it, just the same that I have never seen a paper that conclusively argues that Neanderthals lacked fur as we do, being our nearest cousins it is logical to think that they were a lot like ourselves. 

But regardless of the thornier issue of skin color, it's probable that at least many Neanderthals had brown eyes and dark hair and also a less hyper-pale skin shade than often misrepresented. In this sense I welcome the news because painting Neanderthals as ultra-Nordics, when they lived largely in Southern Europe and even West Asia was really overdoing it towards the side of pseudoscience. 

Echoes from the Past (Mar 16)

You know: the stuff that should have been commented if I was perfect or a paid professional - but was not:

Genetics

Pigmentation reasonably predicted

Yan Klimentidis mentions today that, according to a new paper (Cerqueira 2012, pay per view) as much as 64% of skin pigmentation can be predicted from genes (many of them), reaching to as much as 94% with freckles. The rate of success is much lower however for hair and eye color (44% and 36% respectively).

Are Ethiopians genetically adapted to high altitudes?

I'm generally skeptic of claims of genetic adaption to high altitudes when it does not seem to have ever been demonstrated that this adaption is genetic and not just mere biological flexibility caused by living in the area since childhood. In any case, L. Scheinfeldt 2012 (open access) claims that some candidate genes have been identified for the Amhara.

Taurine cattle could descend from as few as 80 female founders ··> R. Bollognino 2012 (ppv).

Human Evolution

Honey and human evolution: surely you never thought about it before, right? Nutritional anthropologist A. Crittenden thinks that honey may have been more important than meat, based on Hadza practices, which include symbiosis (cooperation) with a bird ··> The Rebel Yell.

Did prehistoric climate change affect human evolution the same as other animals? That is what J.R. Stewart and C.B. Stringer argue in a paper (ppv) ··> Science Daily.

Paleolithic

Speculating about Still Bay culture (South Africa) and climate change ··> article by archaeologist J. Tolleson at Nature.

These marks are the first evidence of humans in Ohio

First evidence of hunting in Ohio c. 13,500 years ago ··> Cleveland Museum of Natural History.

Universal rock art script? David Sánchez mentions again[es] (I commented in 2010 too) the unusual hypothesisi of G. von Petzinger on the possibility that some sort of universal script used by hunter-gatherers around the world, as the markings on the walls appear to be roughly the same everywhere. I am rather skeptic though but curious anyhow. Among the links provided some are in English: video, The Guardian, New Scientist, UVic Space and Cambridge University.

Neolithic and Chalcolithic

One of the dolmens found in Alcónetar

Göbekli Tepe attracted worshipers from 500 kilometers around: from Cappadocia and the border of Armenia ··> Live Science. 

Some Neolithic settlers may have arrived to Iberia from North Africa (specifically Oran area) ··> Archaeology News Network.

Chalcolithic settlement found in Galicia, between Carballo and Berdoias, not far from the mamoa (dolmen) of O Valouco, as a highway was being built ··> La Voz de Galicia[es].

Two dolmens found in Alcónetar (Extremadura, Spain) as the water of the reservoir of Alcántara, one of the largest in Europe, recede because of unprecedented drought ··> Hoy[es].

Problems demonstrating positive selection

This is a very interesting paper not because it offers any new striking discovery but because it brings to doubt previous ones and highlights the difficulties in demonstrating beyond reasonable doubt the functional selection in genes allegedly involved in pigmentation, which is one of the most clear differential adaptions among humans.

Johanna Maria de Gujter et al., Contrasting signals of positive selection in genes involved in human skin color variation from tests based on SNP scans and resequencing. Investigative Genetics 2011. Open access.

Importantly most of the discoveries challenged were made by the same team, what is a outstanding example of scientific commitment and self-criticism. Casting doubts and reducing certainty may not be what makes a Nobel Prize but it is how Science advances in fact.

Abstract (provisional)

Background

Numerous genome-wide scans conducted by genotyping previously-ascertained single nucleotide polymorphisms (SNPs) have provided candidate signatures of positive selection in various regions of the human genome, including in genes involved in pigmentation traits. However, it is unclear how well the signatures discovered by such haplotype-based test statistics can be reproduced in tests based on full resequence data. Four genes, OCA2, TYRP1, DCT and KITLG, implicated in human skin color variation, have shown evidence for positive selection in Europeans and East Asians in previous SNP-scan data. In the current study, we resequenced 4.7-6.7 kb of DNA from each of these genes in Africans, Europeans, East Asians and South Asians.

Results

Applying all commonly-used allele frequency distribution neutrality test statistics to the newly generated sequence data provided conflicting results in respect of evidence for positive selection. Previous haplotype-based findings could not be clearly confirmed. The application of Markov Chain Monte Carlo Approximate Bayesian Computation to these sequence data using a simple forward simulator revealed broad posterior distributions of the selective parameters for all four genes providing no support for positive selection. However, when we applied this approach to published sequence data on SLC45A2, another human pigmentation candidate gene, we could readily confirm evidence for positive selection as previously detected with sequence-based and some haplotype-based tests.

Conclusions

Overall, our data indicate that even genes that are strong biological candidates for positive selection and show reproducible signatures of positive selection in SNP scans do not always show the same replicability of selection signals in other tests, which should be considered in future studies on detecting positive selection in genetic data. 

Lack of vitamin D also causes allergies among children

In another example of the critical role that vitamin D plays in human development, it has been demonstrated now that children with low levels of this key nutrient develop allergies.

Vitamin D is relatively difficult to obtain from food (mostly fish) but we make it in our skin when irradiated by sunlight. Skin color variation is directly related to this necessity.

In the past lack of vitamin D in children (or their mothers) has been linked to rickets, incorrect brain development, autoimmune diseases and other immunity related problems. Allergies also fall within the problematic of inappropriate immunity and can well be considered autoimmune diseases, even if often mild and with very specific triggers.

Source: Science Daily.

Ref. Shimi Sharief et al., Vitamin D levels and food and environmental allergies in the United States: Results from the National Health and Nutrition Examination Survey 2005-2006. Journal of Allergy and Clinical Immunology, 2011. Pay per view. 

See also:

• Leherensuge: vitamin D category
• For what they were...: vitamin D category

Vitamin D helps prevent urinary track infections

Vitamin D is one of the most important underlying factors for human pigmentation. We humans need regular supplies of this vitamin, which is seldom found in diet (fish essentially) and therefore Nature has provided us with sort of a photosynthetic skin, which generates the essential nutrient thanks to the energy of the Sun.

That is why humans loss partly their tan as they migrated northwards, where ultra-violet radiation is scarce, at least in winter.

I have on occasion discussed at my old blog Leherensuge several newly found roles of this critical vitamin besides bone formation: brain development, immune system and cholesterol. I have also mentioned a reason for the dark skin dominant in tropical peoples besides sunburns and skin cancer (vitamin B9, folate).

Well, there is yet another reason for the critical importance of vitamin D in our metabolism and coloring, though maybe not too different from one of the above (immune system): an specific defense response has been linked to vitamin D levels:

Olof Hertting et al., Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder. PLoS ONE 2010. Open access.

Abstract

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI.

Some population structured SNPs and also one epigenetic factor

Another more complex, yet still interesting, paper related with population structure in this last issue of PLoS ONE is:

Jingyu Liu et al., Identification of Genetic and Epigenetic Marks Involved in Population Structure. PLoS ONE 2010. Open Access. 

They have detected some SNPs, mostly related to appearance, that seem to weight specially high in population structure at global levels. Interestingly they have also located an epigenetic marker that weights somewhat in the European+African vs. East Asian+Native American axis.

The most relevant population structure SNPs are by this order:

1. Rs16891982, strongly related to the West Eurasian type of depigmentation (SLC45A2), and logically structured along the West Eurasian-Others axis in an almost true/false type of structure, excepting admixed populations.
2. Rs535878, not yet reported at SNPedia. It is structured along the Native American vs. African American+East Asian axis, with West Eurasians and admixed populations being intermediate (but closer to Native Americans). So Native Americans (and West Eurasians to some extent) seem to have the derived allele.
3. Rs13013484, again not reported in SNPedia yet. The structure runs between African Americans and East Asians. With other populations being intermediate (but except Latinos all closer to African Americans). So East Asians (specially) have the derived allele. However notice that the East Asian sample of just one individual is somewhat inconclusive.

There are more SNPs pondered (see table 1) with factor ranking 22nd being 48 methylation sites in 44 genes of 18 chromosomes, affecting specially West Eurasians and Native Americans in opposite senses. In particular the PM20D1 methylated site seems to have some weak but significant selective pressure among West Eurasians (and admixed populations) - see fig.2B.