The Y chromosome may contribute to sex-specific ageing in Drosophila

Abstract

Heterochromatin suppresses repetitive DNA, and a loss of heterochromatin has been observed in aged cells of several species, including humans and Drosophila. Males often contain substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and male flies generally have shorter average life spans than females. Here we show that repetitive DNA becomes de-repressed more rapidly in old male flies relative to females, and repeats on the Y chromosome are disproportionally mis-expressed during aging. This is associated with a loss of heterochromatin at repetitive elements during aging in male flies, and a general loss of repressive chromatin in aged males away from pericentromeric regions and the Y. By generating flies with different sex chromosome karyotypes (XXY females; X0 and XYY males), we show that repeat de-repression and average lifespan is correlated with the number of Y chromosomes. This suggests that sex-specific chromatin differences may contribute to sex-specific aging in flies.

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

“…The toxicity index measures the excess of intact TEs on an SLC, which represents the potential for genome-wide sex-specific mutational load as well as sex-specific genome instability. On the short time scale of individuals, a high toxicity index could lead to larger physiological differences between the two sexes [13]. In the long term, e.g., between populations and species, the accumulation of TEs as measured by the refugium index can have effects on reproductive isolation through TE/repressor mismatches, similarly to the situation in Drosophila [17,52].…”

“…Since only a subset of TE copies are usually capable of (retro)transposition, we propose a "toxicity index" as a quantitative measure for the excess of intact TE copies in the heterogametic vs. homogametic sex through the presence of an SLC (formula 1.2). The term "toxicity" pays tribute to the recently proposed "toxic Y" hypothesis in Drosophila [13], which suggested that an excess of Y-specific active TEs can lead to male-biased transposition and genome instability, together likely detrimental to the genome and the organism. For birds, we calculated the toxicity index as the excess of fl-ERVs carried by diploid females compared to diploid males ( Table 1), suggesting that females with heteromorphic sex chromosomes carried between 28 to 83% more fl-ERVs than males, and that even the emu has 13% more fl-ERVs in females than males despite largely homomorphic sex chromosomes [31,32].…”

“…This Y-linked regulatory variation cannot be explained simply by regulatory variation of the protein-coding genes and it has been proposed that the variability in Y repetitive content and structural variation are responsible for re-shaping the genome-wide heterochromatin landscape [42]. This hypothesis is known as the heterochromatin sink model, suggesting that large heterochromatin blocks on SLCs act as a sink for the heterochromatin machinery and thereby reduce the efficiency of heterochromatin maintenance elsewhere relative to the SLC-lacking sex [13,42].…”

“…Recently, the Y chromosome repeat content has been linked to the destabilisation and loss of heterochromatin, which in turn is correlated to the shorter lifespan of the heterogametic sex [13,43]. 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 [13,44,45] whose expression is unleashed by heterochromatin loss.…”

“…Because of their low gene content and high repeat density, SLCs were thought to not have any effect beyond sex determination and gonadal development, remaining largely understudied or even absent in the majority of the genome assemblies and studies [8]. However, recent studies on SLCs, especially in humans and other model organisms, have shown that they play roles in human diseases [9,10], male infertility [11], determining sex-specific traits [12], shaping the genome-wide heterochromatic landscape [13], exerting epistatic effects [14][15][16], reproductive isolation [17], and suppressing meiotic drivers on other chromosomes (e.g., through RNAi pathways) [18].…”