Interbreeding between archaic human groups and anatomically modern humans commonly occurring in prehistory

Abstract

A hominin bone fragment from Denisova Cave (Russia) was identified among very few archaic human specimens (i.e., Neanderthals and Denisovans) as being the first-generation offspring of a Neanderthal mother and a Denisovan father. The ancient genomic study of this individual, together with previous evidence of interbreeding, suggests that admixture between archaic and modern humans was common. Here, we review the evidence for hominin interbreeding and the impact of introgressed archaic human DNA on modern humans. As the recovery of human remains in the Pleistocene is extremely rare, a collagen fingerprinting method, often referred to as Zooarchaeology by Mass Spectrometry (ZooMS), was applied to identify over 2000 fragmented bones from Denisova Cave with one being of hominin origin. This individual, named Denisova 11, had her genome sequenced to an average coverage of 2.6-fold. Her mitochondrial DNA was found to be of the Neanderthal type and direct radiocarbon dating showed her to be more than 50000 years old. Approximately equal proportions of Neanderthal-like and Denisovan-like alleles were found in the Denisova 11 individual. This can be explained by her belonging to a population with mixed Neanderthal and Denisovan ancestry, or by her parents being from each one of these two groups. After excluding any accidental mixing of DNA in the laboratory or systematic errors in data processing, analysis of the individual’s alleles carried by two randomly drawn DNA fragments indicated that she had a Neanderthal mother and a Denisovan father. Interbreeding between archaic and modern humans outside Africa was confirmed by a series of studies since the draft sequence of the Neanderthal genome was published in 2010; non-Africans today are the products of this mixture. The proportion of Neanderthal ancestry is significantly higher in present-day East Asians (2.3%−2.6%) than in Western Eurasians (1.8%−2.4%). This has been explained by two independent Neanderthal gene flow events, a later out-of-Africa migration that diluted the proportion of Neanderthal ancestry in Western Eurasian ancestors, or by purifying selection in different population groups. A recent study found that African populations have more Neanderthal ancestry than previously thought, which can be explained by back-migration of Europeans carrying Neanderthal ancestry into Africa. Another widely-known archaic human group, the Denisovans, was identified by the ancient DNA extracted from a finger bone found in Denisova Cave. Along with the high proportion (~5%) of ancestry contributed to present-day Melanesians in Oceania, Denisovans also contributed ~0.2% to the ancestry of mainland Asian and Native American populations. Genes flow into Denisovans from Neanderthals and an unknown hominin (“super-archaic”) were also suggested by ancient DNA studies. Archaeological, ancient genomic, and ancient protein studies suggest Denisovans may have had a wide ecological and geographic distribution. Overall, frequent admixture among different human groups resulted in ~2% Neanderthal ancestry in all non-African humans and up to 5% Denisovan ancestry in some present-day Oceanians. The introgressed archaic human DNA in present-day humans have been affected by natural selection, and inferences about the functional, evolutionary, and phenotypic significance reveal both positive and negative effects. Functional regions of modern human genomes have fewer archaic alleles than expected under a neutral demographic model, which suggests a reduced fitness of some archaic alleles in modern humans. Many Neanderthal variants associated with phenotypes and susceptibility to diseases have been identified in present-day non-Africans, such as type 2 diabetes, lupus, biliary cirrhosis, etc. However, many of the introgressed tracts are also functionally important and possibly helped modern humans adapt to different environments, such as high altitude and latitude areas. For example, the EPAS1 and WARS2/TBX15 , are associated with a high-altitude and high-latitude adaptation in Tibetans and Greenlandic Inuits, respectively. These findings illustrate that admixture with archaic humans has provided genetic variation that helped humans adapt to new environments and has continued to shape our biology. We expect that in the future there will be more evidence of interbreeding between humans in different areas and time periods, adding more details to human genetic history.