While “toxic masculinity” may seem intimately linked to the human species, the fruit fly Drosophila has come to show us that their Y-chromosome acts as a source of genomic male “toxicity” that epigenetic silencing keeps in check.
Specifically, we know that the formation of silent heterochromatin domains during development represses the activity of transposable elements (TEs) present in the eukaryotic genome and inhibits the introduction of potentially “toxic” mutations. Researchers led by Doris Bachtrog (University of California, Berkeley) recently explored the link between genome toxicity in males and the presence of their TE-laden Y-chromosome, which can cause problems if repressive epigenetic mechanisms fail.
Wei and colleagues compared Drosophila species whose males possess distinct Y-chromosomes and found that the epigenetic status of the Y-chromosome helps to control the extent of male toxicity:
- After the maternal-to-zygotic transition, male embryos express higher levels of TEs compared to females due to the contribution of the Y-chromosome
- Increased Y-linked TE expression leads to increased numbers of de novo insertions in males, thereby creating an increased mutational burden compared to females
- TE expression in males diminishes during development in a Drosophila species with an older and smaller Y-chromosome (D. pseudoobscura), while a Drosophila species with a younger and larger Y-chromosome (D. miranda) displayed much higher levels of TE expression
- A lower level of H3K9me3 enrichment, a heterochromatic modification, on the larger D. miranda Y-chromosome associates with elevated TE expression
- Interestingly, the larger D. miranda Y-chromosome contains many actively transcribed genes due to its formation as a fusion between an autosome and the ancestral Y-chromosome, which mediated a dramatic expansion via the accumulation of TEs
Overall, the authors put forward a model in which the open/active chromatin profile associated with actively transcribed genes on the D. miranda Y-chromosome creates a conflict with the heterochromatin domains required to silence TE expression, thereby leading to the acceleration of genomic male toxicity in this species!
See “Y” chromosome size matters in Nature Communications, November 2020.