The naked carp (Gymnocypris przewalskii) is a native teleost of Lake Qinghai (altitude, 3.2 km) on the Qinghai-Tibet Plateau in China. Hypoxia-inducible factor (HIF)-1alpha of Gymnocypris przewalskii was cloned and a phylogenetic tree for vertebrate HIF-1alpha was constructed. By analysis of maximum likelihood models of codon substitutions for HIF-1alpha, three positive sites in the branch lineages of crucian carp, eelpout, and flounder, and a higher proportion of neutral sites in naked carp, antarctic eelpout, rainbow trout, and grayling, were detected among all teleosts. It seems that low habitat temperatures relax the purifying selection of HIF-1alpha in these stenothermal coldwater fish, and both cold and hypoxic lake water contributed to the evolution of the HIF-1alpha gene in the naked carp. Furthermore, Glut 1 mRNA, a gene downstream from HIF-1alpha, has a time-course- and tissue-specific dependent response to hypoxic challenge.
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