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.

More details on the Neanderthal legacy in modern humans

Is straight hair Neanderthal?

A quick note on two recent studies on the relevance of Neanderthal introgression on modern Humankind, notably the "out of Africa" branch.

Sriran Sankararaman et al., The genomic landscape of Neanderthal ancestry in present-day humans. Nature 2014. Pay per view → LINK [doi:doi:10.1038/nature12961]

Abstract

Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture1, 2. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci1, 3, 4, 5, 6, 7, 8. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans9. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes10, 11, 12. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

→ Synthesis at Science Daily.

B. Bernot & J.M. Akey, Resurrecting Surviving Neandertal Lineages from Modern Human Genomes. Science 2014. Pay per view → LINK [doi:10.1126/science.1245938]

Abstract

Anatomically modern humans overlapped and mated with Neandertals such that non-African humans inherit ~1-3% of their genomes from Neandertal ancestors. We identified Neandertal lineages that persist in the DNA of modern humans, in whole-genome sequences from 379 European and 286 East Asian individuals, recovering over 15 Gb of introgressed sequence that spans ~20% of the Neandertal genome (FDR = 5%). Analyses of surviving archaic lineages suggests that there were fitness costs to hybridization, admixture occurred both before and subsequent to divergence of non-African modern humans, and Neandertals were a source of adaptive variation for loci involved in skin phenotypes. Our results provide a new avenue for paleogenomics studies, allowing substantial amounts of population-level DNA sequence information to be obtained from extinct groups even in the absence of fossilized remains.

→ Synthesis at Science Daily.

I don't have access to the papers (update: I do have the second one now) but, honestly, I don't have time either, so, even with full access, I would have to be rather shallow, given the complexity of the matter.

Nevertheless I would highlight the following:

Fitness costs

Areas of dense gene presence tend to be more depleted of Neanderthal inheritance, meaning that, at least in many cases Neanderthal genes were deleterious (harmful) in the context of the H. sapiens genome. It's probable that they worked better in their "native" context of the Neanderthal genome but we must not understimate the risks of low genetic diversity, a problem that affected Neanderthals as well as H. heidelbergensis (species probably including Denisovans or at least their non-Neanderthal ancestry).

Partial hybrid infertility

The areas of very low Neanderthal genetic influence include those of reproductive relevance, including genes affecting the testes and the chromosome X. This is typical of the hybrid infertility phenomenon, which is part of species divergence, making more difficult or even impossible that hybrids can reproduce. This particular item emphasizes that the differential speciation of Neanderthals and H. sapiens was in a quite advance stage already some 100 Ka ago, what does not seem too consistent with the lowest estimates for the divergence of both human species (H. sapiens have been diverging for some 200 Ka and are still perfectly inter-fertile). 

Adaptive Neanderthal hair introgression

On the other hand the Neanderthal genetic legacy has been best preserved in genes that appear to affect keratin (affecting skin, nails and hair). This bit I consider of particular interest because, based on the modern distribution of hair texture phenotypes, I have often speculated that straight hair may be a Neanderthal heritage and this finding seems supportive of my speculation.

It's possible that straight hair conferred some sort of advantage in some of the new areas colonized by H. sapiens, maybe providing better insulation against rain or cold (the ancestral Sapiens thinly curly hair phenotype is probably an adaption to tropical climate, allowing for a ventilated insulation of the head).

Some 20% of the Neanderthal genome still lives in us

Collectively, that is. The actual expressed genes are probably a quite less important proportion anyhow and the actual individual Neanderthal legacy (expressing genes and junk together) seldom is greater than 3% in any case.

Elephant hair density helps cooling

The low density of elephant hair has been demonstrated to help cooling:

Conor L. Myrvhold. What Is the Use of Elephant Hair? PLoS ONE 2012. Open access ··> LINK [doi:10.1371/journal.pone.0047018]

At low densities, hair has almost no effect on air flow and does not trap an insulating air layer near the skin, but the extended hair acts as a pin fin that increases thermal exchanges with the surrounding air. Thus, as the hair density decreases from that of very furry animals, a break-even point is reached where the hair function switches from an insulator to a heat exchanger. This break-even point occurs at a density of about 0.3 million hairs/m² [26] for thick hair covers with creeping flow in between (recall that 1500 hairs/m² is about the maximum density of elephants). For comparison, the hair density of the human head is about 2 million hairs/m² (see Methods and Discussion S1).

These heat dispersal properties were already known for plants (leaf hair, cactus' spines) but it is the first time to be demonstrated for an animal, more specifically a mammal like us. 

Figure 1. Pictures of elephant hair on the top of the back of an Asian elephant, (A) and an African elephant’s head (B).

The presence of hair on elephants was first noted by van Leeuwenhoek [30]. Photos taken by Conor L. Myhrvold in the Woodland Park Zoo, Seattle, Washington, from outside of the elephant enclosure, with permission from the Zoo.

I searched online for hair density on human body (the question we all have in mind, right?) and I could only find a commercial reference (I'd appreciate a better one if you know one). Still it seems that the hair density on tights and legs (and therefore probably on most of the body) in humans is 50 hairs/cm², what translates as 0.5 million hairs/m², somewhat (but not a lot) above the threshold mentioned above.

I'd dare suspect that this means that human body hair (vellus) is for most people thermally neutral but then I wonder how it works with sweat, which is a key part of our tropical thermo-regulatory natural design. Elephants and plants do not sweat (although they do get wet on occasion), so it may well work somewhat different for them.

That seems to be an interesting challenge to explore.