Adaptation across an extreme elevational gradient in Andean leaf-eared mice, the world's highest-dwelling mammal.
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| Title: | Adaptation across an extreme elevational gradient in Andean leaf-eared mice, the world's highest-dwelling mammal. |
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| Authors: | Liphardt, Schuyler (AUTHOR), Bautista, Naim M. (AUTHOR), Quiroga-Carmona, Marcial (AUTHOR), Herrera, Nathanael D. (AUTHOR), Blumer, L. Moritz (AUTHOR), Opazo, Juan C. (AUTHOR), Hoffmann, Federico G. (AUTHOR), Saleem, Ranim (AUTHOR), Somo, Derek A. (AUTHOR), Del Basto Llancaqueo, Francisco (AUTHOR), Thurman, Timothy J. (AUTHOR), Wheeler, Timothy B. (AUTHOR), Shaw, Daniel E. (AUTHOR), Walt, Hunter K. (AUTHOR), Harter, Till S. (AUTHOR), McClelland, Grant B. (AUTHOR), Scott, Graham R. (AUTHOR), Sabat, Pablo (AUTHOR), Cheviron, Zachary A. (AUTHOR), D'Elía, Guillermo (AUTHOR) |
| Source: | Science. 7/9/2026, Vol. 393 Issue 6807, p1-20. 20p. |
| Subjects: | Mice, Altitudes, Biotransformation (Metabolism), Hypoxemia, Oxidative phosphorylation, Population genetics, Heat capacity, Biological adaptation |
| Geographic Terms: | Andes |
| Abstract: | Andean leaf-eared mice (Phyllotis vaccarum) live at the highest elevations of any mammal, and they also have the broadest elevational range, from sea level to mountain summits of >6700 meters. Highland populations have evolved an enhanced thermogenic capacity in hypoxia relative to lowland conspecifics, and this improved physiological performance is associated with an increased mitochondrial respiratory capacity in skeletal muscle. Population genomic analyses identified mechanisms of hypoxia adaptation and revealed an unanticipated dimension of environmental adaptation in P. vaccarum because selection on biotransformation pathways suggests an evolved capacity to metabolize plant-derived dietary toxins. The world's highest-dwelling mammal has adapted to habitats at both the low- and high-elevation limits of its range, and much of the elevation-related selection relates to previously unappreciated aspects of feeding ecology. Editor's summary: Ecosystems at extremely high elevations present challenges that restrict animals from living there. The Andean leaf-eared mouse occupies the highest elevations of any known mammal but also lives at sea level. Liphardt et al. studied these mice across their elevational range and found that the ones living at the highest elevations had enhanced thermogenic capacity in hypoxia and increased mitochondrial capacity, and this local adaptation was maintained in the face of gene flow (see the Perspective by Dearing). The mice have also evolved the ability to eat toxic plants, further facilitating their existence in especially harsh environments. —Sacha Vignieri INTRODUCTION: Andean leaf-eared mice (Phyllotis vaccarum) live on the summits of >6700-m volcanoes in the Puna de Atacama, far surpassing the known elevational range limits of all other terrestrial vertebrates. Such elevations were previously thought to be uninhabitable by mammals owing to severe hypoxia and frigid temperatures. In addition to holding the record as the highest-dwelling mammal, P. vaccarum also has the broadest elevational range because it is distributed from sea level along the desert coast of northern Chile up to the crest of the Andean Cordillera. In this work, we integrate physiological experiments and genomic analyses to gain insights into mechanisms of physiological adaptation to extreme elevations in P. vaccarum. RATIONALE: The notable distribution of P. vaccarum provides an opportunity to investigate physiological mechanisms of local adaptation, including evolved mechanisms of resistance to hypoxic cold stress at the extreme upper limits of the species' elevational range. RESULTS: Analysis of whole-genome sequence variation revealed that P. vaccarum exhibits an unexpected lack of population structure across a >6700-m sea-to-summit elevational gradient on the western slope of the Andes. The lack of population structure indicates that local adaptation to different elevational zones would require very strong divergent selection to counteract the homogenizing effect of gene flow. To assess phenotypic evidence of local adaptation, we tested for elevational differentiation in whole-animal performance (thermogenic capacity) and subordinate physiological traits that contribute to resistance to hypoxic cold stress. At simulated elevations up to 7000 m, common-garden experiments revealed that highland P. vaccarum mitigated the expected decline in thermogenic capacity more effectively than both lowland conspecifics and the strictly lowland congener, P. darwini. Consistent with population differences in whole-animal aerobic performance in hypoxia, highland natives also exhibited a significantly higher mitochondrial respiratory capacity in skeletal muscle. To dissect the genetic basis of local adaptation, we surveyed whole-genome sequence variation to identify candidate genes for elevation-related selection. Identified candidates for high-elevation adaptation were enriched for genes involved in lipid oxidation and synthesis and mitochondrial oxidative phosphorylation, consistent with measured metabolic phenotypes in highland mice. The population genomic analyses also revealed notable evidence for elevation-related selection on biotransformation genes that play key roles in antioxidant defense and the metabolism of dietary toxins, and such genes showed evidence for local adaptation associated with both low- and high-elevation environments. Genomic and transcriptomic variation across the elevational gradient suggest that variation in biotransformation pathways may reflect elevational variation in the composition of food plants that are defended by different sets of toxic secondary compounds. CONCLUSION: We discovered mechanisms of adaptation to hypoxic cold stress, and our experiments provide insights into the physiological features that make up an adaptive metabolic phenotype at extremely high elevations. Our genomic analysis also revealed an unanticipated dimension of environmental adaptation in P. vaccarum because pervasive selection on biotransformation pathways suggests an evolved capacity to metabolize plant-derived dietary toxins. The world's highest-dwelling mammal has adapted to habitats at both the low- and high-elevation limits of its range, and much of the elevation-related selection relates to previously unappreciated aspects of feeding ecology. Physiological experiments and genomic analyses reveal mechanisms of adaptation to extreme elevations in Andean leaf-eared mice.: On the western slope of the Andes, these mice have an extraordinarily broad elevational distribution, from sea level to >6700-m mountain summits. Highland natives have evolved an enhanced thermogenic capacity in hypoxia in conjunction with changes in underlying metabolic phenotypes. Genomic analysis identified candidate genes for elevation-related selection. VO2max, maximal rate of O2 consumption; COX, cytochrome c oxidase; PBE, population branch excess. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Andean leaf-eared mice (Phyllotis vaccarum) live at the highest elevations of any mammal, and they also have the broadest elevational range, from sea level to mountain summits of >6700 meters. Highland populations have evolved an enhanced thermogenic capacity in hypoxia relative to lowland conspecifics, and this improved physiological performance is associated with an increased mitochondrial respiratory capacity in skeletal muscle. Population genomic analyses identified mechanisms of hypoxia adaptation and revealed an unanticipated dimension of environmental adaptation in P. vaccarum because selection on biotransformation pathways suggests an evolved capacity to metabolize plant-derived dietary toxins. The world's highest-dwelling mammal has adapted to habitats at both the low- and high-elevation limits of its range, and much of the elevation-related selection relates to previously unappreciated aspects of feeding ecology. Editor's summary: Ecosystems at extremely high elevations present challenges that restrict animals from living there. The Andean leaf-eared mouse occupies the highest elevations of any known mammal but also lives at sea level. Liphardt et al. studied these mice across their elevational range and found that the ones living at the highest elevations had enhanced thermogenic capacity in hypoxia and increased mitochondrial capacity, and this local adaptation was maintained in the face of gene flow (see the Perspective by Dearing). The mice have also evolved the ability to eat toxic plants, further facilitating their existence in especially harsh environments. —Sacha Vignieri INTRODUCTION: Andean leaf-eared mice (Phyllotis vaccarum) live on the summits of >6700-m volcanoes in the Puna de Atacama, far surpassing the known elevational range limits of all other terrestrial vertebrates. Such elevations were previously thought to be uninhabitable by mammals owing to severe hypoxia and frigid temperatures. In addition to holding the record as the highest-dwelling mammal, P. vaccarum also has the broadest elevational range because it is distributed from sea level along the desert coast of northern Chile up to the crest of the Andean Cordillera. In this work, we integrate physiological experiments and genomic analyses to gain insights into mechanisms of physiological adaptation to extreme elevations in P. vaccarum. RATIONALE: The notable distribution of P. vaccarum provides an opportunity to investigate physiological mechanisms of local adaptation, including evolved mechanisms of resistance to hypoxic cold stress at the extreme upper limits of the species' elevational range. RESULTS: Analysis of whole-genome sequence variation revealed that P. vaccarum exhibits an unexpected lack of population structure across a >6700-m sea-to-summit elevational gradient on the western slope of the Andes. The lack of population structure indicates that local adaptation to different elevational zones would require very strong divergent selection to counteract the homogenizing effect of gene flow. To assess phenotypic evidence of local adaptation, we tested for elevational differentiation in whole-animal performance (thermogenic capacity) and subordinate physiological traits that contribute to resistance to hypoxic cold stress. At simulated elevations up to 7000 m, common-garden experiments revealed that highland P. vaccarum mitigated the expected decline in thermogenic capacity more effectively than both lowland conspecifics and the strictly lowland congener, P. darwini. Consistent with population differences in whole-animal aerobic performance in hypoxia, highland natives also exhibited a significantly higher mitochondrial respiratory capacity in skeletal muscle. To dissect the genetic basis of local adaptation, we surveyed whole-genome sequence variation to identify candidate genes for elevation-related selection. Identified candidates for high-elevation adaptation were enriched for genes involved in lipid oxidation and synthesis and mitochondrial oxidative phosphorylation, consistent with measured metabolic phenotypes in highland mice. The population genomic analyses also revealed notable evidence for elevation-related selection on biotransformation genes that play key roles in antioxidant defense and the metabolism of dietary toxins, and such genes showed evidence for local adaptation associated with both low- and high-elevation environments. Genomic and transcriptomic variation across the elevational gradient suggest that variation in biotransformation pathways may reflect elevational variation in the composition of food plants that are defended by different sets of toxic secondary compounds. CONCLUSION: We discovered mechanisms of adaptation to hypoxic cold stress, and our experiments provide insights into the physiological features that make up an adaptive metabolic phenotype at extremely high elevations. Our genomic analysis also revealed an unanticipated dimension of environmental adaptation in P. vaccarum because pervasive selection on biotransformation pathways suggests an evolved capacity to metabolize plant-derived dietary toxins. The world's highest-dwelling mammal has adapted to habitats at both the low- and high-elevation limits of its range, and much of the elevation-related selection relates to previously unappreciated aspects of feeding ecology. Physiological experiments and genomic analyses reveal mechanisms of adaptation to extreme elevations in Andean leaf-eared mice.: On the western slope of the Andes, these mice have an extraordinarily broad elevational distribution, from sea level to >6700-m mountain summits. Highland natives have evolved an enhanced thermogenic capacity in hypoxia in conjunction with changes in underlying metabolic phenotypes. Genomic analysis identified candidate genes for elevation-related selection. VO2max, maximal rate of O2 consumption; COX, cytochrome c oxidase; PBE, population branch excess. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.aec8347 |
