The costs of being male: are there sex-specific effects of uniparental mitochondrial inheritance?

Abstract

Eukaryotic cells typically contain numerous mitochondria, each with multiple copies of their own genome, the mtDNA. Uniparental transmission of mitochondria, usually via the mother, prevents the mixing of mtDNA from different individuals. While on the one hand, this should resolve the potential for selection for fast-replicating mtDNA variants that reduce organismal fitness, maternal inheritance will, in theory, come with another set of problems that are specifically relevant to males. Maternal inheritance implies that the mitochondrial genome is never transmitted through males, and thus selection can target only the mtDNA sequence when carried by females. A consequence is that mtDNA mutations that confer male-biased phenotypic expression will be prone to evade selection, and accumulate. Here, we review the evidence from the ecological, evolutionary and medical literature for male specificity of mtDNA mutations affecting fertility, health and ageing. While such effects have been discovered experimentally in the laboratory, their relevance to natural populations—including the human population—remains unclear. We suggest that the existence of male expression-biased mtDNA mutations is likely to be a broad phenomenon, but that these mutations remain cryptic owing to the presence of counter-adapted nuclear compensatory modifier mutations, which offset their deleterious effects.

Intergenomic Interactions in Hybrids Between Short-Lived and Long-Lived Lines of a Seed Beetle: Analyses of Life History Traits

“…Although longevity of both sexes was affected by foreign mitochondria, reproduction was much more costly for males than for females with disrupted mitonuclear genome combinations (Table 2). In theory, tied mitonuclear allelic interactions could have been accomplished because of genomes' coevolution that facilitated more efficient metabolic function related to our selection regimes, or because of compensatory evolution in nuclear genome which counteracted mutations accumulated in mtDNA (Dobler et al 2014;Beekman et al 2014). According to the ''mother's curse'' (Gemmell et al 2004) or ''sex-specific selective sieve'' hypothesis (Innocenti et al 2011) the second mechanism is more likely to beset males than females, because there is no direct selection upon mitochondrial function in males due to the maternal pattern of mitochondrial transmission and, therefore, mitochondrial haplotypes could harbor male-biased mitochondrial mutation loads that specifically influence components of ageing in males (Beekman et al 2014).…”

Experimental Support That Natural Selection Has Shaped the Latitudinal Distribution of Mitochondrial Haplotypes in Australian Drosophila melanogaster

“…This polymorphism is therefore a candidate SNP 220 in conferring sex-specific outcomes in heat tolerance, although we cannot rule out the possibility that further variation within the non-coding region of the mtDNA sequence and regulatory elements (which we did not sequence) contributed to this effect. Nonetheless, the observed pattern associated with this sub-haplotype is striking in the context of a hypothesis proposed by Frank and Hurst (1996), often called Mother's Curse, which proposes that 225 maternal inheritance of the mitochondria will facilitate the accumulation of mtDNA mutations that are deleterious to males, but benign or only slightly deleterious to females (Frank and Hurst 1996;Gemmell, et al 2004;Beekman, et al 2014). However, while this haplotype harbours variation that causes a male-limited reduction in heat tolerance, it did not confer a detrimental effect on male capacity to tolerate cold stress (Table S3, Figure 3D).…”

Sex differences in disease genetics

“…Sex-dependent genetic effects have long been known, with good evidence coming from 12 studies of Mendelian sex-linked disorders, narrow-sense heritability, and linkage mapping of quantitative 13 traits (Ober, Loisel, and Gilad 2008). Finally, the mitochondria, which is maternally-inherited and shows 14 a strong sex differences in function, harbours many disease-causing mutations which effect predominantly 15 males (Beekman, Dowling, and Aanen 2014).…”