The history and evolution of the Denisovan- EPAS1 haplotype in Tibetans

Abstract

Recent studies suggest that admixture with archaic hominins played an important role in facilitating biological adaptations to new environments. For example, interbreeding with Denisovans facilitated the adaptation to high-altitude environments on the Tibetan Plateau. Specifically, the EPAS1 gene, a transcription factor that regulates the response to hypoxia, exhibits strong signatures of both positive selection and introgression from Denisovans in Tibetan individuals. Interestingly, despite being geographically closer to the Denisova Cave, East Asian populations do not harbor as much Denisovan ancestry as populations from Melanesia. Recently, two studies have suggested two independent waves of Denisovan admixture into East Asians, one of which is shared with South Asians and Oceanians. Here, we leverage data from EPAS1 in 78 Tibetan individuals to interrogate which of these two introgression events introduced the EPAS1 beneficial sequence into the ancestral population of Tibetans, and we use the distribution of introgressed segment lengths at this locus to infer the timing of the introgression and selection event. We find that the introgression event unique to East Asians most likely introduced the beneficial haplotype into the ancestral population of Tibetans around 48,700 (16,000–59,500) y ago, and selection started around 9,000 (2,500–42,000) y ago. Our estimates suggest that one of the most convincing examples of adaptive introgression is in fact selection acting on standing archaic variation.

Darwin’s finches - an adaptive radiation constructed from ancestral genetic modules

“…Intermediate frequencies, indicative of balanced polymorphism, provide the underlying variation for selection to sort adaptive haplotypes during speciation. Our findings support previous suggestions that ancestral variants contribute to phenotypic diversity, as indicated for pigmentation phenotypes among other songbird species ( 8, 13 ), colour morphs in the common wall lizard ( 44 ), colour patterns in Heliconius butterflies ( 11 ), various phenotypic traits in cichlids ( 7, 9 ), craniofacial morphology in pupfish ( 45 ), winter coat in snow-shoe hares ( 46 ), and adaptation to high altitude in humans ( 47 ). That ancestral variation can be retained in large populations preceding speciation is illustrated in Atlantic herring and stickleback where ecotypes show differences in the frequency of haplotype blocks at hundreds of loci, all underlying ecological adaption ( 48, 49 ).…”

On the Apportionment of Archaic Human Diversity

“…The only exception are Denisovan-unique variants, where the majority of alleles are unique to South Asia and to a smaller degree East Asia (Figure 3C). There is evidence of at least two distinct introgression events in the history of modern human populations, from highly diverged Denisovan-like populations, and Denisovan ancestry of early East Asians correlates with that in present-day East Asian and Austronesian populations, but not South Asian ones [18,20,54,55,63]. This suggest that it is possible that East Asian and South Asian populations received genomic contributions from distinct Denisovan populations.…”

The evolution of human music in light of increased prosocial behavior: a new model

“…Recently, ancient mitochondrial DNA from Denisovans was detected in the sediments from Baishiya Karst Cave on the northeastern edge of the Tibetan Plateau, Gansu, China, indicating the Denisovan presence at about 100, 60, and possibly 45 kya [319]. The presence of a Denisovan EPAS1 gene that aids highaltitude survival in modern-day Tibetans suggests that Denisovans were mountain-dwellers [320]. The nuclear DNA sequence diversity among the Denisovans exceeded that of Neandertals, but was much lower than among present-day humans, which indicates that Denisovans were more successful than Neanderthals in adapting to the harsh Siberian climate -persisting in the Altai region for at least 60,000 years [321].…”