Abstract
Mitochondrial DNA (mtDNA) is predominately uniparentally transmitted. This results in organisms with a single type of mtDNA (homoplasmy), but two or more mtDNA haplotypes have been observed in low frequency in several species (heteroplasmy). In this review, we aim to highlight several aspects of heteroplasmy regarding its origin and its significance on mtDNA function and evolution, which has been progressively recognized in the last several years. Heteroplasmic organisms commonly occur through somatic mutations during an individual’s lifetime. They also occur due to leakage of paternal mtDNA, which rarely happens during fertilization. Alternatively, heteroplasmy can be potentially inherited maternally if an egg is already heteroplasmic. Recent advances in sequencing techniques have increased the ability to detect and quantify heteroplasmy and have revealed that mitochondrial DNA copies in the nucleus (NUMTs) can imitate true heteroplasmy. Heteroplasmy can have significant evolutionary consequences on the survival of mtDNA from the accumulation of deleterious mutations and for its coevolution with the nuclear genome. Particularly in humans, heteroplasmy plays an important role in the emergence of mitochondrial diseases and determines the success of the mitochondrial replacement therapy, a recent method that has been developed to cure mitochondrial diseases.
Highlights
The strict maternal transmission of Mitochondrial DNA (mtDNA) results in homoplasmic individuals, who typically have a single mtDNA haplotype, the maternal one
Heteroplasmy shifts happen due to random segregation of the mtDNA haplotypes to the daughter cells, but, if a mutation has a strong effect on the cellular function, purifying selection will act to eliminate it
It seems that both drift and selection shape heteroplasmy dynamics in individuals and in populations
Summary
The strict maternal transmission of mtDNA results in homoplasmic individuals, who typically have a single mtDNA haplotype, the maternal one. Given that the uniparental transmission of the mtDNA is one of the most general rules in biology and that mtDNA has been extensively used as a genetic marker for phylogenetic studies due to its maternal transmission, the scarce evidence for mtDNA heteroplasmy in the late 1980s and 1990s attracted attention from the scientific community. Heteroplasmy was considered as an interesting exception of the strict maternal mtDNA inheritance. Heteroplasmy has been extensively studied thanks to the modern sequencing techniques. These studies, most of which were conducted in model organisms, revealed that heteroplasmy was more widespread than it was previously believed, as low frequency variants [5], and that both drift and selection play a role in its dynamics within individuals and among generations
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