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Detection of recent natural selection is a challenging problem in population genetics. Here we introduce the singleton density score (SDS), a method to infer very recent changes in allele frequencies from contemporary genome sequences. Applied to data from the UK10K Project, SDS reflects allele frequency changes in the ancestors of modern Britons during the past ~2OOO to 3000 years. We see strong signals of selection at lactase and the major histocompatibility complex, and in favor of blond hair and blue eyes. For polygenic adaptation, we find that recent selection for increased height has driven allele frequency shifts across most of the genome. Moreover, we identify shifts associated with other complex traits, suggesting that polygenic adaptation has played a pervasive role in shaping genotypic and phenotypic variation in modern humans.

Pigmentation is a polygenic trait encompassing some of the most visible phenotypic variation observed in humans. Here we present direct estimates of selection acting on functional alleles in three key genes known to be involved in human pigmentation pathways— HERC2 , SLC45A2 , and TYR —using allele frequency estimates from Eneolithic, Bronze Age, and modern Eastern European samples and forward simulations. Neutrality was overwhelmingly rejected for all alleles studied, with point estimates of selection ranging from around 2–10% per generation. Our results provide direct evidence that strong selection favoring lighter skin, hair, and eye pigmentation has been operating in European populations over the last 5,000 y.

Hair, skin and eye colors are highly heritable and visible traits in humans. We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions—four not previously implicated in the normal variation of human pigmentation—and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2 , and the sixth encompasses previously described variants in MC1R . This is an issue edsumm for 13. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence shows that sea surface temperatures near the North Pole increased from roughly 18 degrees Celsius to over 23 degrees Celsius — such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming.

A complete pre-agricultural European human genome from a ∼7,000-year-old Mesolithic skeleton suggests the existence of a common genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic, and ancestral alleles in several skin pigmentation genes suggest that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Last of the hunter-gatherers The emergence of agriculture is thought to have caused many of the evolutionary changes in human physiology evident in the fossil record. Precisely which changes it is hard to say in the absence of a baseline — a record of human physiology just before the advent of farming. We may now have that in the form of a genome of a Mesolithic hunter-gatherer from Spain, described by Carles Lalueza-Fox and colleagues this week. The genes of this male, who lived around 7,000 years ago, had more in common with ancient genomes from Siberia than with other Europeans, suggesting a wide if thinly spread genetic continuity across Eurasia. He would have been lactose intolerant and less able to digest starchy foods than Neolithic farming people, suggesting that these changes came in with agriculture. He would also have had the unusual combination of dark skin and blue eyes, suggesting that in Mesolithic times, the transition to a lighter, more modern European skin tone was incomplete and that changes in eye colour came first. Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe 1 , 2 , 3 . The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet 4 . However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12 , a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans. Pigmentation variation in humans is influenced by complex genetic architecture in different populations. Here, the authors perform a genome-wide association analysis involving > 6,000 Latin Americans for pigmentation of skin and eyes, and identify known and novel genetic associations.

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.

The eye color of birds, generally referring to the color of the iris, results from both pigmentation and structural coloration. Avian iris colors exhibit striking interspecific and intraspecific variations that correspond to unique evolutionary and ecological histories. Here, we identified the genetic basis of pearl (white) iris color in domestic pigeons ( Columba livia ) to explore the largely unknown genetic mechanism underlying the evolution of avian iris coloration. Using a genome-wide association study (GWAS) approach in 92 pigeons, we mapped the pearl iris trait to a 9 kb region containing the facilitative glucose transporter gene SLC2A11B . A nonsense mutation (W49X) leading to a premature stop codon in SLC2A11B was identified as the causal variant. Transcriptome analysis suggested that SLC2A11B loss of function may downregulate the xanthophore-differentiation gene CSF1R and the key pteridine biosynthesis gene GCH1 , thus resulting in the pearl iris phenotype. Coalescence and phylogenetic analyses indicated that the mutation originated approximately 5,400 years ago, coinciding with the onset of pigeon domestication, while positive selection was likely associated with artificial breeding. Within Aves, potentially impaired SLC2A11B was found in six species from six distinct lineages, four of which associated with their signature brown or blue eyes and lack of pteridine. Analysis of vertebrate SLC2A11B orthologs revealed relaxed selection in the avian clade, consistent with the scenario that during and after avian divergence from the reptilian ancestor, the SLC2A11B-involved development of dermal chromatophores likely degenerated in the presence of feather coverage. Our findings provide new insight into the mechanism of avian iris color variations and the evolution of pigmentation in vertebrates.

Sulem et al . report two previously unknown loci associated with variation in pigmentation in Northern Europeans. In two separate studies, Brown et al . and Gudbjartsson et al . report that some variants affecting human pigmentation, including variants on 20q11.22 near ASIP , also confer risk of cutaneous melanoma and basal cell carcinoma. We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R .

Abstract The iris of the eye shows striking color variation across vertebrate species, and may play important roles in crypsis and communication. The domestic pigeon (Columba livia) has three common iris colors, orange, pearl (white), and bull (dark brown), segregating in a single species, thereby providing a unique opportunity to identify the genetic basis of iris coloration. We used comparative genomics and genetic mapping in laboratory crosses to identify two candidate genes that control variation in iris color in domestic pigeons. We identified a nonsense mutation in the solute carrier SLC2A11B that is shared among all pigeons with pearl eye color, and a locus associated with bull eye color that includes EDNRB2, a gene involved in neural crest migration and pigment development. However, bull eye is likely controlled by a heterogeneous collection of alleles across pigeon breeds. We also found that the EDNRB2 region is associated with regionalized plumage depigmentation (piebalding). Our study identifies two candidate genes for eye colors variation, and establishes a genetic link between iris and plumage color, two traits that vary widely in the evolution of birds and other vertebrates.

Birds exhibit striking variation in eye color that arises from interactions between specialized pigment cells named chromatophores. The types of chromatophores present in the avian iris are lacking from the integument of birds or mammals, but are remarkably similar to those found in the skin of ectothermic vertebrates. To investigate molecular mechanisms associated with eye coloration in birds, we took advantage of a Mendelian mutation found in domestic pigeons that alters the deposition of yellow pterin pigments in the iris. Using a combination of genome-wide association analysis and linkage information in pedigrees, we mapped variation in eye coloration in pigeons to a small genomic region of ~8.5kb. This interval contained a single gene, SLC2A11B , which has been previously implicated in skin pigmentation and chromatophore differentiation in fish. Loss of yellow pigmentation is likely caused by a point mutation that introduces a premature STOP codon and leads to lower expression of SLC2A11B through nonsense-mediated mRNA decay. There were no substantial changes in overall gene expression profiles between both iris types as well as in genes directly associated with pterin metabolism and/or chromatophore differentiation. Our findings demonstrate that SLC2A11B is required for the expression of pterin-based pigmentation in the avian iris. They further highlight common molecular mechanisms underlying the production of coloration in the iris of birds and skin of ectothermic vertebrates.