Maternal inheritance of mitochondria: implications for male fertility?

Abstract

Evolutionary theory predicts maternal inheritance of the mitochondria will lead to the accumulation of mutations in the mitochondrial DNA (mtDNA) that impair male fertility, but leave females unaffected. The hypothesis has been referred to as 'Mother's Curse'. There are many examples of mtDNA mutations or haplotypes, in humans and other metazoans, associated with decreases in sperm performance, but seemingly few reports of associations involving female reproductive traits; an observation that has been used to support the Mother's Curse hypothesis. However, it is unclear whether apparent signatures of male bias in mitochondrial genetic effects on fertility reflect an underlying biological bias or a technical bias resulting from a lack of studies to have screened for female effects. Here, we conduct a systematic literature search of studies reporting mitochondrial genetic effects on fertility-related traits in gonochoristic metazoans (animals with two distinct sexes). Studies of female reproductive outcomes were sparse, reflecting a large technical sex bias across the literature. We were only able to make a valid assessment of sex specificity of mitochondrial genetic effects in 30% of cases. However, in most of these cases, the effects were male biased, including examples of male bias associated with mtDNA mutations in humans. These results are therefore consistent with the hypothesis that maternal inheritance has enriched mtDNA sequences with mutations that specifically impair male fertility. However, future research that redresses the technical imbalance in studies conducted per sex will be key to enabling researchers to fully assess the wider implications of the Mother's Curse hypothesis to male reproductive biology.Reproduction (2018) 155 R159-R168

Maternal age effects on fecundity and offspring egg‐to‐adult viability are not affected by mitochondrial haplotype

“…In sum, our results suggest that mutation accumulation in the mitochondrial genome is not a key driver of reproductive trait senescence in females. Indeed, we did not uncover mitochondrial genetic variation affecting any of the traits measured in this study, a finding that reinforces the emerging evidence that functional effects of mitochondrial genetic variation are often male‐biased (Vaught & Dowling, ). Notwithstanding, we currently have a poor understanding for how mitochondrial genetic effects on organismal life histories will manifest across different ecological and nuclear genetic contexts, and when it comes to studies of mitochondrial effects on reproductive trait expression, there is a lack of studies investigating effects in females.…”

“…That we found no evidence of mtDNA contributing to variation in the rate of female reproductive trait senescence is consistent with recent findings that suggest that purifying selection is highly efficient at shaping the mtDNA sequence through females (Cooper et al., ; Popadin, Nikolaev, Junier, Baranova, & Antonarakis, ). Indeed, a systematic review of effects of mtDNA variation on components of male and female reproductive success across metazoans revealed male biases, suggesting that purifying selection on mtDNA tends to remove functional variation that negatively affects females (Vaught & Dowling, ). Accordingly, previous studies that leveraged these same 13 strains of flies have demonstrated that males, but not females, vary among mitochondrial haplotypes in longevity and rate of senescence (Camus et al., , ), and expression of genes tied to reproductive function (Innocenti et al., ).…”

“…Sequence variation in mitochondrial DNA (mtDNA) is a pervasive characteristic across eukaryotes, but the functional and evolutionary significance of much of this variation remains unclear (Dobler, Rogell, Budar, & Dowling, ; Dowling, Friberg, & Lindell, ; Galtier, Nabholz, Glémin, & Hurst, ). While evolutionary biologists traditionally assumed that mitochondrial genomes evolved under a neutral equilibrium model and that mtDNA variation would not affect phenotype, this assumption has been challenged by numerous studies that have shown that mitochondrial haplotypes commonly affect the expression of a broad range of phenotypic traits, including senescence, fertility, and longevity (Dobler et al., ; Dowling, ; Dowling et al., ; Galtier et al., ; Vaught & Dowling, ).…”

“…studies that have shown that mitochondrial haplotypes commonly affect the expression of a broad range of phenotypic traits, including senescence, fertility, and longevity (Dobler et al, 2014;Dowling, 2014;Dowling et al, 2008;Galtier et al, 2009;Vaught & Dowling, 2018).…”

Sperm competitive advantage of a rare mitochondrial haplogroup linked to differential expression of mitochondrial oxidative phosphorylation genes

“…At its most fundamental level, sex is defined by the relative size of the gametes. Females produce few, large eggs provisioned with thousands of quiescent mitochondria, whereas males produce many motile sperm fuelled by few but metabolically active mitochondria (Vaught & Dowling, 2018;Zeh & Zeh, 2005). Sex-specific selection is therefore likely to be most extreme on mitochondrial function in gametes and gonads, and sperm and testes are predicted to be particularly vulnerable to mother's curse (Frank & Hurst, 1996;Vaught & Dowling, 2018;Zeh & Zeh, 2005).…”