Inferring human phenotypes using ancient DNA: from molecules to populations

Abstract

The increasing availability of ancient DNA (aDNA) from human groups across space and time has yielded deep insights into the movements of our species. However, given the challenges of mapping from genotype to phenotype, aDNA has revealed less about the phenotypes of ancient individuals. In this review, we highlight recent advances in inferring ancient phenotypes — from the molecular to population scale — with a focus on applications enabled by new machine learning approaches. The genetic architecture of complex traits across human groups suggests that the prediction of individual-level complex traits, like behavior or disease risk, is often challenging across the relevant evolutionary distances. Thus, we propose an approach that integrates predictions of molecular phenotypes, whose mechanisms are more conserved, with nongenetic data.