Evolution and plasticity of the control of breathing in high-altitude natives: Insights from deer mice

pressure. In contrast, high-altitude populations do not express VAH, but instead exhibit a fixed increase in total ventilation in hypoxia and a deeper more effective breathing pattern than lowlanders. Studies of F2 inter-population hybrids suggested that these evolved changes in breathing in highlanders could be largely attributed to sequence variants in two genes. Specifically, the more effective breathing pattern of highlanders was associated with genetic variation in α-globin, whereas the lack of VAH was associated with variation in the hypoxia-inducible factor 2α (HIF-2α) gene Epas1. However, in contrast to the lack of plasticity in highlanders during adulthood alone, life-long hypoxia exposure throughout development and adulthood has a strong effect on the HVR, further augmenting total ventilation and tidal volume. Altogether, these findings in deer mice suggest that the control of breathing in high-altitude natives is shaped by the integration of their unique genotype and developmental environment, improving resilience to harsh and hypoxic environments.