Alternative splicing tunes sex differences in flies
The Y chromosome has an unanticipated role in sex-biased intron retention in Drosophila.
Differences between males and females in sexually dimorphic species stem in part from disparities in gene expression. This sex-biased expression can be achieved through numerous means, one of which is alternative splicing. In a recent study, Wang et al. investigated differences in one type of alternative splicing, called intron retention, in male and female fruit flies—and, in the process, they discovered an unanticipated role for the Y chromosome.
To survey intron retention in five parts of the fly (accessory gland, brain, ovary, testis, and whole body), the team used RNA-seq data from both the modENCODE project and their own lab. They found intron retention was pervasive: across all tissues of both sexes, they identified 21,664 instances of intron retention, the majority of which were previously unknown.
The retained introns most often interrupted coding sequences and included a premature stop codon. Since transcripts with premature stop codons are often targeted for nonsense-mediated decay, this intron retention could be a means of downregulating the genes in question. Among the genes with the most intron retention in the testis compared to the ovary were many involved in egg formation, lending credence to the idea that the intron retention is used to downregulate these genes. Also supporting this notion, Wang et al. found that transcripts with greater intron retention in one sex were also less abundant in that sex. However, it is possible that some transcripts with retained introns could yield functional proteins, opening the possibility that sex-biased intron retention could be used for more than simple downregulation of genes—a topic for future study.
Unexpectedly, the group also found that females carrying a Y chromosome in addition to their usual two X chromosomes had differences in intron retention compared to XX female flies. These differences were similar to the ones they observed when they compared intron retention in wild-type flies’ testes and ovaries, demonstrating that the mere presence of a Y chromosome has a major impact on intron retention. The Y chromosome in fruit flies—as in humans— contains a small number of protein-coding genes. By demonstrating the powerful effect a Y chromosome can have on intron retention, this study provides valuable insight into the often-unrecognized functions of sex chromosomes.
The Y Chromosome Modulates Splicing and Sex-Biased Intron Retention Rates in Drosophila
Meng Wang, Alan T. Branco, Bernardo Lemos
Genetics 2018 208: 1057-1067; https://doi.org/10.1534/genetics.117.300637