Mitochondrial Changes and Sequence Migration to the Nucleus

Mitochondria are organelles located with the eukaryotic cell that are involved in energy production, and are thought to originate from bacteria ancestrally engulfed by eukaryotic cells. Mitochondrial DNA (mtDNA) is circular, transcribed separately from nuclear DNA, and has a comparatively high mutation rate (10 times or more higher than nuclear DNA in mammals). One consequence is co-evolution of nuclear- and mtDNA-encoded electron transport chain genes, preventing nuclear transfer between many primates and possibly compromising nuclear transplantation within human lineages. It is inherited maternally in the majority of eukaryotes, and analyses of mtDNA are used to probe phylogeny among closely related species and lineages within humans. Humans have elevated mtDNA transition (but not transversion) mutation rates compared to other primates examined. mtDNA has inserted into the nucleus and become incorporated into nuclear genomic DNA at multiple points during eukaryotic evolution, and these mitochondrial pseudogenes in the nuclear genome (NUMTs) have duplicated further in primates in the setting of nuclear segmental duplications. Multiple original mtDNA insertions and NUMT duplications are unique to the human lineage and 27 NUMTs have been identified that are human-specific. A recent review of the subject has also evaluated mitochondrial divergence since the pan-homo split. Within the hominin lineage, sequence analyses of the Denisovan, Neanderthal and modern human mitochondrial genomes suggest that Denisovans diverged from the Neanderthal-human lineage substantially earlier than the Neanderthals. Analyses of nuclear DNA, meanwhile, suggests that Neanderthals and Denisovans may be less distant from one another, highlighting the utility of analyzing both mitochondrial and nuclear DNA when determining evolutionary relationships.