Nat Ecol Evol. 2023 June 12. DOI: 10.1038/s41559-023-02089-7

Y chromosome toxicity does not contribute to sex-specific differences in longevity

Rénald Delanoue1, Charlène Clot1, Chloé Leray1, Thomas Pihl1, Bruno Hudry1


1Université Côte d’Azur, CNRS, Inserm, IBV, Nice, France.


While sex chromosomes carry sex-determining genes, they also often differ from autosomes in size and composition, consisting mainly of silenced heterochromatic repetitive DNA. Even though Y chromosomes show structural heteromorphism, the functional significance of such differences remains elusive. Correlative studies suggest that the amount of Y chromosome heterochromatin might be responsible for several male-specific traits, including sex-specific differences in longevity observed across a wide spectrum of species, including humans. However, experimental models to test this hypothesis have been lacking. Here we use the Drosophila melanogaster Y chromosome to investigate the relevance of sex chromosome heterochromatin in somatic organs in vivo. Using CRISPR–Cas9, we generated a library of Y chromosomes with variable levels of heterochromatin. We show that these different Y chromosomes can disrupt gene silencing in trans, on other chromosomes, by sequestering core components of the heterochromatin machinery. This effect is positively correlated to the level of Y heterochromatin. However, we also find that the ability of the Y chromosome to affect genome-wide heterochromatin does not generate physiological sex differences, including sexual dimorphism in longevity. Instead, we discovered that it is the phenotypic sex, female or male, that controls sex-specific differences in lifespan, rather than the presence of a Y chromosome. Altogether, our findings dismiss the ‘toxic Y’ hypothesis that postulates that the Y chromosome leads to reduced lifespan in XY individuals.


DOI: 10.1038/s41559-023-02089-7