Altitude adaptation in Tibet caused by introgression of Denisovan-like DNA

By E. Huerta-Sánchez, Xin Jin, Asan, Zhuoma Bianba, B. Peter, N. Vinckenbosch, Yu Liang, X. Yi, Mingze He, M. Somel and 15 more. Nature, 2014

962 citations recorded by the source corpus.

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.

Subfields: Clinical Biochemistry, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9d067f608295f3eab689ea91400a0f8baf468d8d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

A framework for incorporating evolutionary genomics into biodiversity conservation and management (2015, background): “With our own species, researchers estimate that whilst less than 7% of our genome is introgressed with the DNA of extinct hominid species, the captured DNA sequences have helped humans adapt to a variety of climates and resist pathogens [211,212,218].”
Using the Neandertal genome to study the evolution of small insertions and deletions in modern humans (2017, neutral): “We calculated the probability of a region to retain a length of at least ~180 kb if it was generated by incomplete lineage sorting (see [9, 38]) and found that this scenario is unlikely (p = 0.”
Demographic History and Genetic Adaptation in the Himalayan Region Inferred from Genome-Wide SNP Genotypes of 49 Populations (2018, background): “None of the top selection candidate regions, apart from EPAS1 (Huerta-Sanchez et al. 2014; Hu et al. 2017), show signatures of adaptive introgression from archaic Denisovans or Neanderthals according to published introgression maps (Sankararaman et al. 2016).”
Ancient DNA and the rewriting of human history: be sparing with Occam’s razor (2016, background): “Allele frequencies in ancient populations are replotted f from theoretical models of selection based only on present-day population alleles in Eurasians in the past was similar to that in present-day Near Easte started in Paleolithic times (SLC24A5) or in Neolithic times (TLR1, NOD2 and Denisovans [”
An Evolutionary Anthropological Perspective on Modern Human Origins (2015, background): “The fossil hominins from Sima de los Huesos (Atapuerca, Spain) have morphological affinities to Neanderthals (Stringer 2012) but genetically group closer with Denisovans (Meyer et al 2014) and are imprecisely dated from ~600-300 ka.”
Robust and scalable inference of population history from hundreds of unphased whole-genomes (2016, background): “Apart from its intrinsic interest, such knowledge is useful for understanding patterns of historical migration 1–4 , natural selection 1,5,6 , the relationship between humans and other hominids 7–10 , and even distantly related phenomena like global climate change 11,12 .”