Mother's curse is pervasive across a large mitonuclearDrosophilapanel

Abstract

The maternal inheritance of mitochondrial genomes entails a sex‐specific selective sieve, whereby mutations in mitochondrial DNA can only respond to selection acting on females. In theory, this enables male‐harming mutations to accumulate in mitochondrial genomes as long as they are neutral, beneficial, or only slightly deleterious to females. Ultimately, this bias could drive the evolution of male‐specific mitochondrial mutation loads, an idea known as mother's curse. Earlier work on this hypothesis has mainly used small Drosophila panels, in which naturally sourced mitochondrial genomes were coupled to an isogenic nuclear background. The lack of nuclear genetic variation in these designs has precluded robust generalization. Here, we test the predictions of mother's curse using a large Drosophila mitonuclear genetic panel, comprising nine isogenic nuclear genomes coupled to nine mitochondrial haplotypes, giving a total of 81 different mitonuclear genotypes. Following a predictive framework, we tested the mother's curse hypothesis by screening our panel for wing size. This trait is tightly correlated with overall body size and is sexually dimorphic in Drosophila. Moreover, growth is heavily reliant on metabolism and mitochondrial function, making wing size an ideal trait for the study of the impact of mitochondrial variation. We detect high levels of mitonuclear epistasis, and more importantly, we report that mitochondrial genetic variance is larger in male than female Drosophila for eight out of the nine nuclear genetic backgrounds used. These results demonstrate that the maternal inheritance of mitochondrial DNA does indeed modulate male life history traits in a more generalisable way than previously demonstrated.

Mitonuclear interactions alter sex-specific longevity in a species without sex chromosomes

“…The most rigorous tests of the Mother's Curse hypothesis have been conducted in Drosophila, where some studies find support for the hypothesis (e.g. [13][14][15][16][17][18]) while others do not (e.g. [19,20]).…”

Mitonuclear interactions produce extreme differences in response to redox stress

“…Most people differ from each other in at least as many SNPs in mtDNA as the fly lines reported here, but in addition of course vary in nuclear alleles, which would be expected to modulate risk. We know from mitochondrial diseases that nuclear variations can indeed suppress or unmask severe symptoms 52 , and we have found similar effects in a large panel of fly lines in which 9 different mtDNAs were set against 9 different nuclear backgrounds (81 mitonuclear genotypes) 53 . But the extent to which ordinary SNPs in both mitochondrial and nuclear genes influence life-long health, risk of disease and drug responses is simply unknown.…”

Developmental rate displays effects of inheritance but not of sex in inter-population hybrids ofTigriopus californicus

“…For example, the 'mother's curse' hypothesis posits that mutations in mitochondrial DNA causing beneficial interactions in females will accumulate, even if they cause negative interactions in males, due to the lack of paternal transmission of mitochondrial DNA (Frank & Hurst, 1996;Gemmell et al, 2004). Consistent with these expectations, effects of mitonuclear interactions aligning with the 'mother's curse' have been observed for many traits (Rand et al, 2001;Camus et al, 2012;Milot et al, 2017;Carnegie et al, 2021, although see Mossman et al, 2016aMossman et al, , 2016bMossman et al, , 2017Eyre-Walker, 2017;Rand & Mossman, 2020). Taken together, it is clear not only that mitonuclear incompatibilities can have substantial fitness effects, but also that resolving the impacts of heritability and sex on traits associated with these interactions is critical for understanding the role of mitonuclear incompatibility in outbreeding depression, early-stage reproductive isolation and speciation.…”