PT - JOURNAL ARTICLE AU - Zahida Sultanova AU - Philip A. Downing AU - Pau Carazo TI - Genetic sex determination and sex-specific lifespan in tetrapods – evidence of a toxic Y effect AID - 10.1101/2020.03.09.983700 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.03.09.983700 4099 - http://biorxiv.org/content/early/2020/03/09/2020.03.09.983700.short 4100 - http://biorxiv.org/content/early/2020/03/09/2020.03.09.983700.full AB - Sex-specific lifespans are ubiquitous across the tree of life and exhibit broad taxonomic patterns that remain a puzzle, such as males living longer than females in birds and vice versa in mammals. The prevailing “unguarded-X” hypothesis (UXh) explains this by differential expression of recessive mutations in the X/Z chromosome of the heterogametic sex (e.g., females in birds and males in mammals), but has only received indirect support to date. An alternative hypothesis is that the accumulation of deleterious mutations and repetitive elements on the Y/W chromosome might lower the survival of the heterogametic sex (“toxic Y” hypothesis). Here, we report lower survival of the heterogametic relative to the homogametic sex across 138 species of birds, mammals, reptiles and amphibians, as expected if sex chromosomes shape sex-specific lifespans. We then analysed bird and mammal karyotypes and found that the relative sizes of the X and Z chromosomes are not associated with sex-specific lifespans, contrary to UXh predictions. In contrast, we found that Y size correlates negatively with male survival in mammals, where toxic Y effects are expected to be particularly strong. This suggests that small Y chromosomes benefit male lifespans. Our results confirm the role of sex chromosomes in explaining sex differences in lifespan, but indicate that, at least in mammals, this is better explained by “toxic Y” rather than UXh effects.