EXPANDING THE FUNCTIONAL HUMAN MITOCHONDRIAL-DNA DATABASE BY THE ESTABLISHMENT OF PRIMATE XENOMITOCHONDRIAL CYBRIDS

The nuclear and mitochondrial genomes coevolve to optimize approximate ly 100 different interactions necessary for an efficient ATP-generatin g system, This coevolution led to a species-specific compatibility bet ween these genomes, We introduced mitochondrial DNA (mtDNA) from diffe rent primates into mtDNA-less human cells and selected for growth of c ells with a functional oxidative phosphorylation system, mtDNA from co mmon chimpanzee, pigmy chimpanzee, and gorilla were able to restore ox idative phosphorylation in the context of a human nuclear background, whereas mtDNA from orangutan, and species representative of Old-World monkeys, New-World monkeys, and lemurs were not, Oxygen consumption, a sensitive index of respiratory function, showed that mtDNA from chimp anzee, pigmy chimpanzee, and gorilla replaced the human mtDNA and rest ored respiration to essentially normal levels, Mitochondrial protein s ynthesis was also unaltered in successful ''xenomitochondrial cybrids, '' The abrupt failure of mtDNA from primate species that diverged from humans as recently as 8-18 million years ago to functionally replace human mtDNA suggests the presence of one or a few mutations affecting critical nuclear-mitochondrial genome interactions between these speci es, These cellular systems provide a demonstration of intergenus mtDNA transfer, expand more than 20-fold the number of mtDNA polymorphisms that can be analyzed in a human nuclear background, and provide a nove l model for the study of nuclear-mitochondrial interactions.