Relative rates of evolution of male-beneficial nuclear compensatory mutations and male-harming Mother's Curse mitochondrial alleles.

Mother's Curse alleles represent a significant source of potential male fitness defects. The maternal inheritance of mutations with the pattern of sex-specific fitness effects, s♀>0>s♂, allows Mother's Curse alleles to spread through a population even though they reduce male fitness. Although the mitochondrial genomes of animals contain only a handful of protein-coding genes, mutations in many of these genes have been shown to have a direct effect on male fertility. The evolutionary process of nuclear compensation is hypothesized to counteract the male-limited mitochondrial defects that spread via Mother's Curse. Here we use population genetic models to investigate the evolution of compensatory autosomal nuclear mutations that act to restore the loss of fitness caused by mitochondrial mutation pressures. We derive the rate of male fitness deterioration by Mother's Curse and the rate of restoration by nuclear compensatory evolution. We find that the rate of nuclear gene compensation is many times slower than that of its deterioration by cytoplasmic mutation pressure, resulting in a significant lag in the recovery of male fitness. Thus, the numbers of nuclear genes capable of restoring male mitochondrial fitness defects must be large in order to sustain male fitness in the face of mutation pressures.

Maternal inheritance, such as that of the mitochondrial genome, allows genetic variants that benefit female survival and reproduction to spread even when they negatively impact male fitness, referred to as Mother's Curse alleles. The maintenance of male fitness in spite of such alleles is predominantly attributed to the spread of variants in the nuclear genome that compensate for the male harming effects. However, the relative rate of nuclear compensatory evolution has not been derived. Here we show that many features of nuclear compensatory mutations slow their rate of evolution many-fold relative to the rapid spread of Mother's Curse alleles. Thus, the pool of nuclear genes capable of compensating for mitochondria-associated male harm must be very large to maintain male fitness, especially in light of the potential contribution of male-harming effects from the maternally inherited microbiome.