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

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 large TE-rich neo-Y
chromosome, resulting in up-regulation of Y-linked TEs already in young
males. This is consistent with an interaction between the 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.