Toxic Y chromosome: Increased repeat expression and age-associated heterochromatin loss in male Drosophila with a young Y chromosome

Author summary Y chromosomes can be toxic. The Y chromosome of many species contains a large number of transposable elements (TEs), which are transcriptionally constrained by repressive chromatin marks. When relieved of these epigenetic modifications, many TEs can readily move from one genomic location to another. We show that TEs located on the Y chromosome are less effectively silenced in male Drosophila, and the toxic Y effect appears more pronounced in a species that contains a larger Y chromosome with more repeats and more actively transcribed genes. Our data demonstrate that repeat-rich Y chromosomes are a genomic liability for males. Sex-specific differences in lifespan are prevalent across the tree of life and influenced by heteromorphic sex chromosomes. In species with XY sex chromosomes, females often outlive males. Males and females can differ in their overall repeat content due to the repetitive Y chromosome, and repeats on the Y might lower survival of the heterogametic sex (toxic Y effect). Here, we take advantage of the well-assembled young Y chromosome of Drosophila miranda to study the sex-specific dynamics of chromatin structure and repeat expression during aging in male and female flies. Male D. miranda have about twice as much repetitive DNA compared to females, and live shorter than females. Heterochromatin is crucial for silencing of repetitive elements, yet old D. miranda flies lose H3K9me3 modifications in their pericentromere, with heterochromatin loss being more severe during aging in males than females. Satellite DNA becomes de-repressed more rapidly in old vs. young male flies relative to females. In contrast to what is observed in D. melanogaster, we find that transposable elements (TEs) are expressed at higher levels in male D. miranda throughout their life. We show that epigenetic silencing via heterochromatin formation is ineffective on the TE-rich neo-Y chromosome, presumably due to active transcription of a large number of neo-Y linked genes, resulting in up-regulation of Y-linked TEs already in young males. This is consistent with an interaction between the evolutionary age of the Y chromosome and the genomic effects of aging. Our data support growing evidence that "toxic Y chromosomes" can diminish male fitness and a reduction in heterochromatin can contribute to sex-specific aging.