Ancient DNA research reveals a new environmental adaptation profile in human populations

Abstract

The origin, peopling and evolution of human beings have all contributed greatly to shaping the genetic diversity of present human populations, and are the research focus of multiple disciplines. Molecular genetics has tried to deduce the human history through genetic analysis of modern human populations. It proposed the well-recognized out of Africa human origin model with Homo sapiens replaced all the other human species. As modern humans migrated out of Africa, they encountered multiple environmental conditions which could exert selection pressure upon them, as exemplified by the evolutionary elucidation of human phenotypes like skin pigmentation and height as well as physiological traits like lactase tolerance, starch digestion, immune response and hypoxia adaptation. However, this indirect approach could be largely influenced by undetected population structure and model parameter settings, still cannot fully reveal the genuine human history, and sometimes could even produce misleading results based on Occam’s razor theory. Recently, whole genome resequencing is used to directly analyse ancient DNA samples collected from different time periods to investigate a specific history event. In addition, the genetic data from both ancient and modern human populations are systematically compared to obtain a more straightforward elucidation of human history. To be more specific, analyses from archaic human populations have demonstrated strong evidence of gene flow between Homo sapiens and other extinct human species, e.g. Neanderthals and the Danisova hominin, which gave rise to a leaky replacement model. That is, other ancient human species also have contributed to modern human populations. Together with the remaining Homo sapien s genome, the introgression from ancient human species went through genetic drift and natural selection. For example, the EPAS1 gene encoding endothelial Per-Arnt-Sim (PAS) domain protein 1 has been indicated to play an important role in hypoxia adaptation among Tibetan individuals. 31 SNPs of this gene are significantly associated with haemoglobin (Hb) levels, and the Tibetan dominant alleles are significantly associated with low Hb levels, a trait featured in Tibetan hypoxia adaptation. Interestingly, the dominant Tibetan haplotype can only be observed in Tibetans and Danisova hominin with high frequency, and further genetic analysis revealed this gene was from Danisova hominin. Similar stories could also be observed for other human phenotypes and physiological traits. Therefore, as demonstrated by the illustrious example of EPAS1 gene, ancient DNA research is revealing a human history far more complex than what we have inferred from parsimonious models based on modern DNA. In this review, we will briefly overview some key events in human environmental adaptation in the light of ancient DNA findings, and discuss new evidence how natural selection has shaped human populations, which might provide clues for future studies.