Identification of human-specific adaptation sites of ATP6.

Mitochondria play an essential role in forming ATP and generating heat. The proportion of these two depends on the coupling efficiency of electrochemical gradient to synthesize ATP. Therefore, an increased basal metabolic rate caused by partial uncoupling of the mitochondria can be balanced by a high caloric intake provided by a high-fat diet. The recent study by Mishmar et al. (Proc. Natl. Acad. Sci. USA 2003; 100: 171-176) suggested that ATP6 was the most variable gene among human mitochondrial DNAs and probably resulted from the adaptation of Homo sapiens to the colder climate during the migration out of Africa. According to this adaptation theory, the ATP6 of Homo sapiens (omnivorous animals consuming fat-containing diet) should be significantly different from that of other primates for permitting human adaptation to the dietary conditions. On the basis of this rationale, we analyzed ATP6 sequences of 136 unrelated Taiwanese subjects, which then were compared with 1,130 reported sequences. The obtained human consensus from 1,266 individuals was compared with that derived from 42 species of primates other than human. The alignment showed that human ATP6 harbored 80 variable residues, among which 25 amino acids were conserved in other primates, suggesting that adaptation constraints operating at the amino acid level results in the species-specific difference of ATP6. Therefore, these 25 amino acids are probably the human-specific adaptation residues of ATP6.