The phenotypic adaptations of high altitude dwellers — Tibetans, Andeans, and Ethiopian highlanders — have been studied for decades. But with recent advances that make genetic sequencing faster and cheaper, Emilia and her colleagues thought that they could throw new light on the problem, perhaps uncovering the genetic basis of the physiological traits that had already been investigated. Next-generation sequencing techniques would allow them to sequence all the genes (technically, all the exons) of a large group of Tibetans and compare them to the same genes in a group of non-altitude-adapted individuals. The Beijing Genomics Institute would collect DNA samples and sequence them; Emilia and her colleagues would do the analytic and statistical work to identify the relevant genes.2
To find the genes involved in altitude adaptation, the researchers decided to look for regions of the genome that showed a “signature of selection” — a sign that the region has recently experienced natural or sexual selection. Their basic approach was to look for alleles that were frequent among highland Tibetans and rare in a nearby lowland population from Beijing, the Han Chinese. The team reasoned that, because the two populations are so closely related, differences in allele frequency between the two were likely caused by recent selection — perhaps the result of the different altitudes at which the two populations live.
2Yi, X., Y. Liang, E. Huerta-Sánchez, X. Jin, Z.X.P. Cuo, J.E. Pool, … and J. Wang. 2010. Sequencing of 50 human exomes reveals adaptation to high altitude. Science 329:75-78.