Incompatibility between Nuclear and Mitochondrial Genomes Contributes to an Interspecies Reproductive Barrier

Abstract

Vertebrate cells carry two different genomes, nuclear (nDNA) and mitochondrial (mtDNA), both encoding proteins in the oxidative phosphorylation. Because of the extensive interactions, adaptive coevolution of the two genomes must occur to ensure normal mitochondrial function. To investigate whether incompatibilities between these two genomes could contribute to interspecies reproductive barriers, we performed reciprocal mtDNA replacement (MR) in zygotes between widely divergent Mus m. domesticus (B6) and a conplastic Mus m. musculus (PWD) mice. Transfer of MR1 cybrid embryos (B6nDNA-PWDmtDNA) supported normal development of F1 offspring with reduced male fertility but unaffected reproductive fitness in females. Furthermore, donor PWD mtDNA was faithfully transmitted through the germline into F2 and F3 generations. In contrast, reciprocal MR2 (PWDnDNA-B6mtDNA) produced high embryonic loss and stillborn rates, suggesting an association between mitochondrial function and infertility. These results strongly suggest that functional incompatibility between nuclear and mitochondrial genomes contributes to interspecies reproductive isolation in mammals.

Maternal inheritance of mitochondria: implications for male fertility?

“…Male offspring carrying PWD mtDNA in a B6 nuclear autosomal background exhibited reduced fertility, as gauged by number of litters produced, but females were unaffected. This male infertility effect is likely attributable to mutations in the mtDNA sequence of the PWD mice, which are normally rescued by modifier mutations that lie within the PWD nuclear background, but which were not present in the experimental mice carrying the B6 background (Ma et al 2016).…”

“…In sum, there have been three studies in mice that have examined effects of mtDNA variation on reproductive outcomes of both sexes (Inoue et al 2000, Nakada et al 2006, Ma et al 2016. Each of these studies has documented male biases in fertility reductions that map to mutations in the mitochondrial genome.…”

“…Mutator males, however, were mostly infertile, with only one of eight males tested producing a litter; and mtDNA-mutator males possessed testes of much smaller size relative to wild-type males, even early in adult life (at 12 weeks). Secondly, Ma et al (2016) created reciprocal (conplastic) combinations of mitochondrial and nuclear genotypes in the zygotes of two divergent mice strains; Mus m. domesticus (B6 strain) and Mus m. musculus (PWD strain) mice. Male offspring carrying PWD mtDNA in a B6 nuclear autosomal background exhibited reduced fertility, as gauged by number of litters produced, but females were unaffected.…”

Paternal chromosome loss and metabolic crisis contribute to hybrid inviability in Xenopus

“…These results are consistent with glycolytic defects as a primary cause of t e × l s hybrid embryo death. However, other defects that contribute to hybrid incompatibility could be masked by the abrupt cell lysis, such as conflicts between the paternal genome and maternal mitochondria 22,23 .…”

Assisted reproductive technologies to prevent human mitochondrial disease transmission

“…PNT has been used for reciprocal mitochondrial exchange between B6 and PWD subspecies of mice that diverged from a common ancestor over 0.5 Myr ago 32 and whose mtDNAs differ by 391 single-nucleotide polymorphisms (SNPs; 2.4% of the mtDNA genome). Post-implantation development of embryos with a B6 nuclear genome and PWD mtDNA (B6-PWD) was similar to controls.…”