Contributions of Neaderthal DNA to phenotypic variation in the modern human

Neanderthals (Homo neanderthalensis) diverged from the modern human (Homo sapiens) lineage ~600,000 years ago in southeast Africa. This diagram should be helpful to “see” the various branches of the Homo tree []:
Interbreeding between Neanderthals and early modern humans appears likely to have occurred in the time from less than ~200,000 years ago, almost up until the time of Neaderthal extinction (which occurred in what is now Europe, ~25,000 years ago). In the genomes of present-day non-Africans, this interbreeding has resulted in ~2% Neanderthal DNA. This Neanderthal DNA can have both positive and negative effects. Together with the rapid decrease in Neanderthal ancestry after introgression, depletion of Neanderthal DNA around functional genomic elements in present-day human genomes suggests that a large fraction of Neanderthal alleles (defined as a gene or DNA segment on at least one chromosome of the chromosome pair) are deleterious to us modern humans. However, recent studies have also identified a number of introgressed Neanderthal alleles that have increased in frequency in modern humans and which might contribute to genetic adaptation to new environmental signals: adaptive variants in genes associated with immunity, skin and hair pigmentation, and metabolism have been identified.

The majority of Neanderthal alleles in the genomes of modern humans today are, however, not strongly adaptive and are therefore present at low frequencies (<2%) in present-day populations. To date, the number of individuals for whom genotype and phenotype information is available has been limited, making it difficult to study archaic alleles that are at such low frequencies or to link them to phenotypic variation (showing different traits). A recent study [Science 2o16; 351: 737–741] used the electronic medical records (EMRs) and genotypes of 28,000 individuals to address the contribution of these less frequent Neanderthal alleles to clinical traits in modern humans. That study showed a large number of Neanderthal variants at different loci influence risk of a number of disease traits –– including depression, skin lesions, and blood-clotting disorders, and that Neanderthals contributed both risk alleles and protective alleles for these traits. However, evaluating the broader contribution of Neanderthals to common phenotypic variation in modern humans, or inferring Neanderthal phenotypes, has not been possible, largely because of the limited number of studies that collect genotype data together with common phenotype information. In addition to collecting genotype data via a custom genotyping array, the UK Biobank has collected baseline phenotypes, including traits related to physical appearance, diet, sun exposure, and behavior, as well as disease, for more than 500,000 people. A pilot dataset including genotypes and phenotypes for more than 150,000 of these individuals was recently made available for study. Using these data, authors [see attached] studied the contribution of Neanderthals to common human phenotypic variation in 112,338 individuals from the UK Biobank –– to determine the set of traits to which Neanderthals have contributed and to evaluate relative contribution of archaic and non-archaic alleles to common phenotypic variation in modern humans. Authors found that Neanderthal DNA affects skin tone, hair color, height, sleeping patterns, mood, and smoking status in present-day Europeans. Intriguingly, multiple Neanderthal alleles at different loci contribute to skin and hair color in present-day Europeans: these alleles contribute to both lighter and darker skin tones and hair color. These data suggest that Neanderthals themselves were most likely variable in these traits.

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