Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

Abstract

The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered.It is currently known that AMH introgressed with archaic hominins once they left the African continent. Current out of African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.Keywords: archaic introgression, fitness, natural selection, Neanderthal, Denisova, anatomically modern humans. Peer-reviewed version available at Genes 2018, 9, 358; doi:10.3390/genes9070358 2 Widespread interbreeding between homininsThe demographic history of anatomically modern humans (AMH) is complex, and involves a large number of migrations, genetic admixtures and introgressions, population extinctions and genetic adaptations, which overlap both in time and in space (see Figure 1). Due to this complexity, the evolutionary history of humankind is still far from being fully understood (Nielsen et al., 2017). During the last 30 years, the most accepted demographic scenario for explaining recent evolution of AMH has been the Out of Africa model (OOA). According to this model, AMH evolved in Africa around 100-200 thousands years ago (kya) in East Africa and migrated to the rest of the world. Classical "pure" OOA assumes that admixture with other archaic populations such as Neanderthals or Denisovans, present at the time of the rise of AMH, either did not occur or was negligible (Lalueza-Fox & Gilbert, 2011). Figure 1. Family tree of the four groups of early humans living in Eurasia 50,000 years ago and the inferred gene flow between the groups due to interbreeding (based on Prüfer et al., 2014;Mondal et al., 2016;Hsieh et al., 2016; Medina-Gomez et al., 2017). The direction and estimated magnitude of inferred gene flow events are shown. Branch lengths and timing of gene flows are not scaled. The dashed line indicates that it is uncertain whether Denisovan gene flow into modern humans in mainland Asia occurred directly or via Oceania. Light violet color indicates introgression events from unknown archaic populations (Ghost).However, genomic studies of ancient DNA have revealed that AMH interbred with other hominid lineages, such as Neanderthals and Denisovans, present in Eurasia up to ∼30,000-50,000 years ago Quach & Quintana-Murci, 2017;Vattathil & Akey, 2015 New studies based on current genetic diversity are suggesting that the events of archaic introgression in AMH did occur out of Africa with other hidden "ghost" archaic populations (Mondal et al., 2016). Furthermore, there i...

Genomics of a complete butterfly continent

“…Although many introgressed genes may be selected against and are being eliminated from modern human genomes with time (75), a fraction of them may be beneficial, increasing their frequency as a result of selection (72). These introgressed genes were proposed to help modern humans adapt to diverse climates (76,77) and fight against pathogens (78,79).…”

What Can Earth History and Evolution Tell About the Creator of the Universe?

“…When this asteroid hit the Earth, it produced the Chicxulub crater in the north of the Yucatan peninsula in Mexico. 32 While the dinosaurs lived, the mammals were small and only of minor importance. Maor et al believe that nocturnality may have allowed mammals to avoid antagonistic interactions with diurnal dinosaurs.…”

“…35 Shortly after this group of Homo sapiens emigrated from Africa, about 55,000-60,000 years ago, they interbred with the Neanderthal Homo neanderthalensis in the Near or Middle East. 36 Hence, all non-Africans today have about 2% 32 of their genetic material from the Neanderthals. 37 This introgression of Neanderthal DNA into modern human genome brought us many advantages, such as an improvement of our immune system 38 and an expansion of our genetic diversity, which had been drastically reduced in the course of emigration from Africa.…”

Inferring archaic introgression from hominin genetic data

“…On the other hand, from the viewpoint of medical genetics and genome wide association studies, it has been argued that archaic introgression contributed variants that underlie several deleterious traits 89 and has been directly selected against 59,84 . While not mutually exclusive, these perspectives highlight another open question in the study of archaic introgression 90 …”