Human Disease-Associated Mitochondrial Mutations Fixed in Nonhuman Primates

A number of human disease-associated sequences have been reported in other species, such as rodents, but compensatory changes appear to prevent these deleterious mutations from being expressed. The aim of this work was to compare the mitochondrial DNA of multiple primates to ascertain whether mitochondrial disease-causing sequences in humans are fixed in nonhuman primates. Indeed, 46 sequences related to human pathology were identified in 1 or more of the 12 studied nonhuman primates, the majority of which were associated with late-onset diseases. Most of these sequences can be explained by the presence of secondary compensatory changes that render these mutations phenotypically inert. Nonetheless, and since humans not only are the longest-lived primate but feature the largest brain, one hypothesis is that a gradual optimization of the human mitochondrion occurred in the hominid lineage driven by the need to optimize the aerobic energy metabolism to delay neurodegeneration. Therefore, it is also proposed that some of these disease-associated sequences in nonhuman primates may be linked to the evolution of human longevity and intelligence, indicating a general pattern of selection on longevity in the course of evolution of the human mitochondrion. [Reviewing Editor: Dr. Martin Kreitman]