Physiology of hypoxia adaptation in the worlds highest-dwelling mammal

This research project is to discover how mice living at extremely high elevations in the Andes are able to survive and function in spite of extreme cold and lack of oxygen (hypoxia). The study species, Phyllotis vaccarum, holds the record as the world’s highest-dwelling mammal, and it also has by far the broadest altitudinal range. The species is continuously distributed from sea level to the crest of the Andes at >6700 m (>22,000’).

Because of its extraordinarily broad elevational range and extreme hypoxia tolerance, Phyllotis vaccarum is an ideal study species to address questions about physiological mechanisms of high-altitude adaptation and the way such mechanisms evolved. The discoveries will provide a basis for comparison with human populations that are native to extremely high elevations in the Andean Altiplano and the Tibetan Plateau, and there is the potential to identify general principles associated with genetic adaptation and physiological acclimatization to extreme environments.

The research is likely to yield novel discoveries because mammals that live at such extreme elevations have never been experimentally studied. The project includes an international exchange program for trainees from the Chilean and North American institutions.

This research project will investigate mechanisms of hypoxia adaptation in an Andean mouse species (Phyllotis vaccarum) that lives at altitudes far higher than any other mammal species in the world and which also has by far the broadest altitudinal range. The research project is designed to address fundamental questions regarding the role of phenotypic plasticity in environmental adaptation and the extent to which acclimatization responses generally align with genetic responses to selection.

Experimental insights into the relative contributions of genetic and environmentally induced changes in hypoxia-responsive phenotypes – and the potential synergy or antagonism between them – will advance our understanding of physiological adaptation and the process by which complex physiological phenotypes evolve. To identify and characterize mechanisms of hypoxia acclimation and adaptation, a common-garden experimental design will be used to examine physiological differences between natural populations of leaf-eared mice sampled from contrasting high- and low-altitude extremes of the species’ range.

The experimental analysis of systemic physiology will involve measurements of whole-animal physiological performance (thermogenic capacity in hypoxia) and a comprehensive set of subordinate traits in pedigreed, captive-bred highland and lowland mice. Since Phyllotis vaccarum lives at altitudes that were previously considered completely uninhabitable, identification of mechanisms of hypoxia adaptation in this vertebrate extremophile will have transformative value in comparative/evolutionary physiology.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.