Evidence for positive selection in relation to tuberculosis in Ecuadorian high-altitude populations before European contact. Ecuador High-Altitude Genomes

Despite ongoing genomic studies from the Andean highlands of Peru, high-altitude adaptation in the region is still poorly understood from a genetic standpoint. To grasp a more diverse perspective of Andean adaptive evolutionary history, we present whole genomes from high-altitude Indigenous populations from Ecuador. Utilizing haplotype, allele-frequency, and admixture-aware methods, we scanned the genomes for putative signals of selection that may correlate with the hypoxia adaptation. We identified regions of the genome that show signals of strong selection to both cardiovascular and hypoxia pathways, which are distinct from those uncovered in Peruvian populations. However, the strongest signals of selection were not related to these pathways but instead to genomic regions involved in the immune response to M. tuberculosis. We further present evidence that the timing of the selection event occurred thousands of years before European contact, suggesting that M. tuberculosis was not only present in the Andean highlands but also that the local Indigenous people were adapted to this bacterium before the arrival of Europeans.