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

Abstract

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.

Transposable element accumulation drives size differences among polymorphic Y chromosomes in Drosophila

“…Thus, the higher repeat content of Y L may indeed dilute heterochromatin components in males with a large Y. Intriguingly, we find that H3K9me3 levels are generally much lower for TE copies located on the Y chromosome compared to autosomes and the X, irrespective of the Y variant (Figure 4A, B; Figure S14, S15). This is consistent with previous findings showing lower levels of heterochromatin enrichment for Y--linked TEs (42,43), and repeat--rich Y chromosomes were found to be associated with the up--regulation of transposable elements in males (41--43). We obtained replicate expression data from heads of young and old Y S and Y L males to quantify TE expression between differently sized Y chromosomes, and during aging.…”

“…Additionally, the presence and the number of Y chromosomes strongly influences genome-wide enrichment patterns of repressive chromatin modifications (40,41), with additional Y chromosomes diminishing the heterochromatin enrichment at highly repetitive regions such as pericentromeres. Larger, more repeat--and gene--rich Y chromosomes were also linked to an up-regulation of transposable elements in males (42,43). These results are generally interpreted as the Y chromosome acting as a heterochromatin sink that re--distributes repressive chromatin marks genome--wide (16).…”

Epigenetic conflict on a degenerating Y chromosome increases mutational burden in Drosophila males

“…5f), and either transposition bias or selection could contribute to the nonrandom spatial distribution of TEs 30 . The elevated rate of somatic TE insertions in D. miranda males is expected to impose a deleterious fitness cost unique to males, and may contribute to the female-biased sex ratio found in this species 31 , and shorter lifespan of D. miranda males compared to females 32 . In addition, if insertions rates are also higher in the male germline, the species as a whole is expected to have a higher mutational TE burden.…”

The avian W chromosome is a refugium for endogenous retroviruses with likely effects on female-biased mutational load and genetic incompatibilities

“…By using Drosophila melanogaster experimental lines with different Y dosages (XO males, XXY females, XYY males), Brown et al [13] showed that the presence and number of Y chromosomes carried are correlated with shorter lifespans. It was thus suggested that the Y itself is “toxic” for the entire genome and organism, and this toxicity is caused by the Y-linked load of active TEs [13,45,46] whose expression is unleashed by heterochromatin loss. Possibly, the dysregulation of TEs due to heterochromatin loss is also associated with laminopathic diseases in Drosophila and humans [47].…”