Evolution for extreme living: variation in mitochondrial cytochrome c oxidase genes correlated with elevation in pikas (genus Ochotona).

The genus Ochotona (pikas) is a clade of cold-tolerant lagomorphs that includes many high-elevation species. Pikas offer a unique opportunity to study adaptations and potential limitations of an ecologically important mammal to high-elevation hypoxia. We analyzed the evolution of 3 mitochondrial genes encoding the catalytic core of cytochrome c oxidase (COX) in 10 pika species occupying elevations from sea level to 5000 m. COX is an enzyme highly reliant on oxygen and essential for cell function. One amino acid property, the equilibrium constant (ionization of COOH), was found to be under selection in the overall protein complex. We observed a strong relationship between the net value change in this property and the elevation each species occupies, with higher-elevation species having potentially more efficient proteins. We also found evidence of selection in low-elevation species for potentially less efficient COX, perhaps trading efficiency for heat production in the absence of hypoxia. Our results suggest that different pika species may have evolved elevation-specific COX proteins, specialization that may indicate limitations in their ability to shift their elevational ranges in response to future climate change.