A mouse that lives higher than any other mammal has evolved unexpected adaptations that allow it to thrive from sea level to Andean summits, researchers report in a new study. According to the findings, the Andean leaf-eared mouse uses a distinct combination of metabolic and genetic adaptations – including an unexpected ability to detoxify poisonous plants – to survive extreme environments. The Andean leaf-eared mouse (Phyllotis vaccarum) is the world’s highest-dwelling mammal and can be found living at elevations exceeding 6,700 meters above sea level. At these highest elevations, air temperatures remain almost permanently below freezing and oxygen levels are only about 44% of those at sea level, creating extreme physiological challenges for mammal survival. However, despite these conditions, leaf-eared mice thrive, occupying habitats spanning from sea level to high-elevation mountain summits. The adaptations that enable this species uniquely to live in such an incredible range of environments, including the thin, freezing air of the Andes, aren’t well understood. Here, Schuyler Liphardt and colleagues analyzed whole-genome sequence data for 167 leaf-eared mice collected from locations across the species’ elevational range. Specimens were collected during 5 extreme high-elevation expeditions in the central Andes and additional low- to mid-elevation surveys. Liphardt et al. compared animals from high elevations with mice from lower elevations and a closely related lowland species. Through laboratory experiments that simulated cold, low-oxygen conditions, they found that high-elevation mice generated significantly more body heat and showed greater activity in both their muscles and heat-producing brown fat, reflecting an enhanced ability to stay warm despite the lack of oxygen. Surprisingly, these mice did not rely on many of the oxygen-transport adaptations seen in other high-altitude mammals, such as changes in hemoglobin. Instead, they appear to depend on a different suite of physiological and genetic adaptations that improve energy production, regulate blood vessels, and help their bodies function under chronic oxygen deprivation. Population genomic analyses found that these adaptations in high-elevation mice are maintained despite substantial gene flow between highland and lowland populations. The authors also found that genomic structural variation does not appear to drive adaptation. Unexpectedly, genomic evidence revealed widespread selection on pathways involved in detoxifying plant-derived compounds, suggesting the species has also evolved the ability to metabolize toxic plants. This indicates that feeding ecology may play a much larger role in elevation-related adaptation than previously recognized.
