Signatures of an archival legacy

April 10, 2021 0 By S Harachand

Neandertals evolved in western Eurasia about half a million years ago. They lived largely separated from the ancestors of modern humans in Africa.

However, interbreeding between Neandertals and early modern humans has been shown to have contributed about 2% Neandertal DNA to the genomes of most living humans, with higher amounts of Neandertal ancestry found outside of Africa.

These archaic hominins continue to have a biological impact on human physiology today through genetic contributions to modern human populations that occurred during the last tens of thousands of years of their existence, according to a study titled The Contribution of Neandertals to Phenotypic Variation in Modern Humans that appeared in AJHG.

Neandertals and other archaic populations inhabited Eurasia for several hundred thousand years and were likely well adapted to their environments. Therefore, some genetic variation inherited from these archaic humans may have been adaptive in modern humans, particularly across phenotypes that are strongly influenced by direct interactions with the surrounding environment, such as the immune response to infectious agents.

The inherited Neandertal DNA has apparently had both positive and negative effects.

The Neandertal ancestry rapidly decreased after introgression. The depletion of Neandertal DNA around functional genomic elements in present-day human genomes suggests that a large fraction of Neandertal alleles are deleterious in modern humans.

Though studies assume that there may have been widespread purifying selection against Neandertal ancestry in humans, some recent research has also identified a number of introgressed Neandertal alleles that have increased in frequency in modern humans. Adaptive variants in genes related to immunity, skin and hair pigmentation, and metabolism have been identified.

The majority of Neandertal alleles in the genomes of people today are, however, not strongly adaptive and are therefore present at low frequencies (<2%) in present-day populations.

A large number of Neandertal variants at different loci influence the risk of a number of disease traits, including depression, skin lesions, and blood-clotting disorders, found a study using the electronic medical records and genotypes of 28,000 individuals to address the contribution of these less frequent Neandertal alleles to clinical traits in modern humans. It showed that Neandertals contributed both risk and protective alleles for these traits.

Largely on the basis of disease cohorts and signatures of positive selection, a number of immune, skin, metabolic, and behavioural phenotypes have been suggested to be influenced by archaic ancestry.