PMC

Population branch statistic (PBS) across chromosome 19 in the Oromos population compared to both the Luhya (LWK) and European (CEU) populations. The red line represents a genome-wide 0.1% FDR. Three distinct regions exceed this cutoff, two of which are near the centromere and were thus not prioritized. The bottom panel shows the SNP frequency profile in the prioritized region for Oromos (blue) and LWK (brown, inverted). Genes with Drosophila orthologs (on which RNAi experiments were conducted) are shown in black below the frequency profiles. As can be seen, variant frequencies in this region are considerably higher in the highlanders than in a nearby lowlander population.

RNAi-mediated knockdown of candidate human gene orthologs enhanced hypoxia tolerance in D. melanogaster. The available UAS-RNAi lines for cic (ortholog of human CIC), Hsl (ortholog of human LIPE) and Paf-AHα (ortholog of human PAFAH1B3) were crossed with the daughterless (da)-GAL4, a driver strain that expresses GAL4 ubiquitously. The level of hypoxia tolerance was determined by measuring eclosion rate in an atmosphere chamber containing 5% O₂. The UAS-RNAi stocks without cross were used as a negative control (open bars). Two different UAS-RNAi lines targeting each candidate gene were used in each experiment to minimize off-target effects. Each bar represents the mean ± standard error of the mean value of three separate tests; *P < 0.05.