July 2, 2014

Altitude-adaption in Tibetans is "Denisovan-like"

It seems that archaic humans left a small but critical legacy among us:

Emilia Huerta Sánchez et al., Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature 2014. Pay per viewLINK [doi:10.1038/nature13408] 

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 plateau1, 2, 3. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans4, 5, 6, 7, 8, 9, 10, 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.

Figure 3: A haplotype network based on the number of pairwise differences between the 40 most common haplotypes.
The haplotypes were defined from all the SNPs present in the combined 1000 Genomes and Tibetan samples: 515 SNPs in total within the 32.7-kb EPAS1 region. The Denisovan haplotypes were added to the set of the common haplotypes. The R software package pegas23 was used to generate the figure, using pairwise differences as distances. Each pie chart represents one unique haplotype, labelled with Roman numerals, and the radius of the pie chart is proportional to the log2(number of chromosomes with that haplotype) plus a minimum size so that it is easier to see the Denisovan haplotype. The sections in the pie provide the breakdown of the haplotype representation amongst populations. The width of the edges is proportional to the number of pairwise differences between the joined haplotypes; the thinnest edge represents a difference of one mutation. The legend shows all the possible haplotypes among these populations. The numbers (1, 9, 35 and 40) next to an edge (the line connecting two haplotypes) in the bottom right are the number of pairwise differences between the corresponding haplotypes. We added an edge afterwards between the Tibetan haplotype XXXIII and its closest non-Denisovan haplotype (XXI) to indicate its divergence from the other modern human groups. Extended Data Fig. 5a contains all the pairwise differences between the haplotypes presented in this figure. ASW, African Americans from the south western United States; CEU, Utah residents with northern and western European ancestry; GBR, British; FIN, Finnish; JPT, Japanese; LWK, Luhya; CHS, southern Han Chinese; CHB, Han Chinese from Beijing; MXL, Mexican; PUR, Puerto Rican; CLM, Colombian; TSI, Toscani; YRI, Yoruban. Where there is only one line within a pie chart, this indicates that only one population contains the haplotype.

See also this entry on Neanderthal introgression being subject to positive and negative selection.


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