According to evolutionary theory, mitochondria could be poisoned gifts that mothers transmit to their sons. This is because mutations harmful to males are expected to accumulate in the mitochondrial genome, the so-called ‘mother’s curse’. However, the contribution of the mother’s curse to the mutation load in nature remains largely unknown and hard to predict, because compensatory mechanisms could impede the spread of deleterious mitochondria. Here we provide evidence for the mother’s curse in action over 290 years in a human population. We studied a mutation causing Leber’s hereditary optical neuropathy, a disease with male-biased prevalence and which has long been suspected to be maintained in populations by the mother’s curse. Male carriers showed a low fitness relative to non-carriers and to females, mostly explained by their high rate of infant mortality. Despite poor male fitness, selection analysis predicted a slight (albeit non-significant) increase in frequency, which sharply contrasts with the 35.5% per-generation decrease predicted if mitochondrial DNA transmission had been through males instead of females. Our results are therefore even suggestive of positive selection through the female line that may exacerbate effects of the mother’s curse. This study supports a contribution of the mother’s curse to the reduction of male lifespan, uncovering a large fitness effect associated with a single mitochondrial variant.
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We thank S. Gravel, L. Barreiro, A. Hodgkinson, J. Moorad, D. H. Nussey and D. Réale for their useful comments that helped improve the manuscript; H. Vézina, M. Jomphe and B. Desjardins for their support in working with the BALSAC register and the RPQA. This study was funded by the Fonds de recherche du Québec—Santé, through the Québec Network of Applied Genetic Medicine (D.L.) and a Natural Sciences and Engineering Research Council of Canada Discovery grant (E.M.).
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Milot, E., Moreau, C., Gagnon, A. et al. Mother’s curse neutralizes natural selection against a human genetic disease over three centuries. Nat Ecol Evol 1, 1400–1406 (2017). https://doi.org/10.1038/s41559-017-0276-6
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