Genomic and functional evidence reveals convergent evolution in fishes on the Tibetan Plateau.

High-altitude environments are strong drivers of adaptive evolution in endemic organisms. However, little is known about the genetic mechanisms of convergent adaptation among different lineages, especially in fishes. There are three independent fish groups on the Tibetan Plateau: Tibetan Loaches, Schizothoracine fishes and Glyptosternoid fishes; all are well adapted to the harsh environmental conditions. They represent an excellent example of convergent evolution but with an unclear genetic basis. We used comparative genomic analyses between Tibetan fishes and fishes from low altitudes and detected genomic signatures of convergent evolution in fishes on the Tibetan Plateau. The Tibetan fishes exhibited genome-wide accelerated evolution in comparison with a control set of fishes from low altitudes. A total of 368 positively selected genes were identified in Tibetan fishes, which were enriched in functional categories related to energy metabolism and hypoxia response. Widespread parallel amino acid substitutions were detected among the Tibetan fishes and a subset of these substitutions occurred in positively selected genes associated with high-altitude adaptation. Functional assays suggested that von Hippel-Lindau (VHL) tumour suppressor genes from Tibetan fishes enhance hypoxia-inducible factor (HIF) activity convergently under hypoxia compared to low-altitude fishes. The results provide genomic and functional evidence supporting convergent genetic mechanisms for high-altitude adaptation in fishes on the Tibetan Plateau.