No evidence for intermolecular recombination in human fibroblast and blood mtDNA from individuals with biparental mtDNA transmission

Abstract

Strictly maternal inheritance and lack of intermolecular recombination of the human mitochondrial genome (mtDNA) are the assumed preconditions for molecular evolution studies, phylogenetic reconstruction and population genetic analyses. This hypothesis, however, has been challenged by investigations providing evidence for genetic recombination of mtDNA, thus sparking controversy. Using single-molecule real-time (SMRT) sequencing technology, we sequenced the entire mtDNA from blood and fibroblast cells from five individuals with biparental mtDNA transmission in three separate, multiple-generation families. After phasing the single nucleotide polymorphism (SNP) genotypes of mtDNA, no intermolecular recombination between paternal and maternal mtDNA was found when the mtDNA was transmitted in either biparental or maternal mode. Our study provides support for the argument that intermolecular mtDNA recombination is absent or extremely rare in humans. As a consequence, these results support the feasibility of mtDNA-based molecular evolution studies and phylogenetic and population genetic analyses for humans, while also avoiding inaccurate phylogenetic inferences and incorrect rejection of the molecular clock.