Mar 052012

A new paper in Human Genetics reports:

We have surveyed 15 high-altitude adaptation candidate decision’s for signals of positive selection in North Caucasian highlanders using targeted re-sequencing. A total of 49 unrelated Daghestani from three ethnic groups (Avars, Kubachians, and Laks) living in ancient villages located at around 2,000 m above sea level were chosen as the study population. Caucasian (Adygei living at sea level, N = 20) and CEU (CEPH Utah residents with ancestry from northern and western Europe; N = 20) were used as controls. Candidate genes were compared with 20 putatively neutral control regions resequenced in the same individuals. The regions of interest were amplified by long-PCR, pooled according to individual, indexed by adding an eight-nucleotide tag, and sequenced using the Illumina GAII platform. 1,066 SNPs were called using false discovery and false negative thresholds of ~6%. The neutral regions provided an empirical null distribution to compare with the candidate genes for signals of selection. Two genes stood out. In Laks, a non-synonymous variant within HIF1A already known to be associated with improvement in oxygen metabolism was rediscovered, and in Kubachians a cluster of 13 SNPs located in a conserved intronic region within EGLN1 showing high population differentiation was found. These variants illustrate both the common pathways of adaptation to high altitude in different populations and features specific to the Daghestani populations, showing how even a mildly hypoxic environment can lead to genetic adaptation.

For some perspective, Denver is 1600 m above sea level, Kabul’s 1800 m, Mexico City’s 2200 m, and the Tibetan Plateau is on average 4500 m.

If you’re familiar with chronic mountain sickness and increased risk of miscarriage for lowland migrants in Tibet or the Andes but aren’t aware of any outcomes worse than marathon victory for highlanders going the other way, this segment should be especially interesting:

When populations of highlanders moved to the lowlands as a consequence of a Soviet government decision [is there any more deadpan a way to put it?] the mortality rate increased dramatically. Although this increased mortality could be partly explained by novel pathogens encountered in the lowlands, it could not be entirely accounted for in this way (Bulaeva et al. 1995, 1996), so might also reflect a reduction of low-altitude fitness due to genetic adaptation to the high altitude or low genetic diversity in these populations.

Bulayeva et al. (2008) have the numbers:

Migrants from highlands to the lowlands experienced dramatically increased morbidity and mortality in 1944–1947: up to 65–70% of total migrants had suffered malaria, typhus and other new infections and about 35–37% of total migrants had died. Genetic-epidemiological study support that non-survived migrants were characterized by a higher inbreeding rate, lower heterozygosity and higher physiological sensitivity to the environmental stress. This inter-connected complex had advantage for adaptation of the highlanders to the native environment but diminished their adaptability in the new and/or changing environment.

And it’s not just men:

As [Tibetan] horses were adjusted [and more than merely acclimated] to life in the mountains, they were inferior to the bigger horses of the steppes and did not stand life in humid plains too well. Therefore, Tibetans fighting in China proper were mostly infantry warriors.

Pagani, L., Ayub, Q., MacArthur, D. G., Xue, Y., Baillie, J. K., Chen, Y., Kozarewa, I., Turner, D. J., Tofanelli, S., Bulayeva, K., Kidd, K., Paoli, G., Tyler-Smith, C. (2012). High altitude adaptation in Daghestani populations from the Caucasus. Hum. Genet., 131, 423-433.

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