Ancestral chromatin configuration constrains chromatin evolution on differentiating sex chromosomes in Drosophila

Abstract

Sex chromosomes evolve distinctive types of chromatin from a pair of ancestral autosomes that are usually euchromatic. In Drosophila, the dosage-compensated X becomes enriched for hyperactive chromatin in males (mediated by H4K16ac), while the Y chromosome acquires silencing heterochromatin (enriched for H3K9me2/3). Drosophila autosomes are typically mostly euchromatic but the small dot chromosome has evolved a heterochromatin-like milieu (enriched for H3K9me2/3) that permits the normal expression of dot-linked genes, but which is different from typical pericentric heterochromatin. In Drosophila busckii, the dot chromosomes have fused to the ancestral sex chromosomes, creating a pair of neo-sex chromosomes. Here we collect genomic, transcriptomic and epigenomic data from D. busckii, to investigate the evolutionary trajectory of sex chromosomes from a largely heterochromatic ancestor. We show that the neo-sex chromosomes formed <1 million years ago, but nearly 60% of neo-Y linked genes have already become non-functional. Expression levels are generally lower for the neo-Y alleles relative to their neo-X homologs, and the silencing heterochromatin mark H3K9me2, but not H3K9me3, is significantly enriched on silenced neo-Y genes. Despite rampant neo-Y degeneration, we find that the neo-X is deficient for the canonical histone modification mark of dosage compensation (H4K16ac), relative to autosomes or the compensated ancestral X chromosome, possibly reflecting constraints imposed on evolving hyperactive chromatin in an originally heterochromatic environment. Yet, neo-X genes are transcriptionally more active in males, relative to females, suggesting the evolution of incipient dosage compensation on the neo-X. Our data show that Y degeneration proceeds quickly after sex chromosomes become established through genomic and epigenetic changes, and are consistent with the idea that the evolution of sex-linked chromatin is influenced by its ancestral configuration.\n\nAuthor SummaryDNA is packaged with proteins into two general types of chromatin: the transcriptionally active euchromatin and repressive heterochromatin. Sex chromosomes typically evolve from a pair of euchromatic autosomes. The Y chromosome of Drosophila is gene poor and almost entirely heterochromatic; the X chromosome, in contrast, has evolved a hyperactive euchromatin structure and globally up-regulates its gene expression, to compensate for loss of activity from the homologous genes on the Y chromosome. The evolutionary trajectory along which sex chromosomes evolve such opposite types of chromatin configurations remains unclear, as most sex chromosomes are ancient and no longer contain signatures of their transitions. Here we investigate a pair of unusual young sex chromosomes (termed neo-Y and neo-X chromosomes) in D. busckii, which formed through fusions of a largely heterochromatic autosome (the dot chromosome) to the ancestral sex chromosomes. We show that nearly 60% of the neo-Y genes have already become non-functional within only 1 million years of evolution. Gene expression is lower on the neo-Y than on the neo-X, which is associated with a higher level of binding of a silencing heterochromatin mark. The neo-X, on the other hand, shows no evidence of evolving hyperactive chromatin for dosage compensation. Our results show that the Y chromosome can degenerate quickly, but the tempo and mode of chromatin evolution on the sex chromosomes may be constrained by the ancestral chromatin configuration.