Battle of the Sex Chromosomes: Competition between X and Y Chromosome-Encoded Proteins for Partner Interaction and Chromatin Occupancy Drives Multicopy Gene Expression and Evolution in Muroid Rodents

• Published in: Molecular biology and evolution 2020-12, Vol.37 (12), p.3453-3468
• Main Authors: Moretti, Charlotte, Blanco, Mélina, Ialy-Radio, Côme, Serrentino, Maria-Elisabetta, Gobé, Clara, Friedman, Robin, Battail, Christophe, Leduc, Marjorie, Ward, Monika A, Vaiman, Daniel, Tores, Frederic, Cocquet, Julie
• Format: Article
• Language: English
• Subjects: Animals; Biodiversity; Biological Evolution; Cell Cycle Proteins - genetics; Development Biology; Discoveries; DNA-Binding Proteins - genetics; Gametogenesis; Life Sciences; Male; Mice, Inbred C57BL; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Populations and Evolution; Protein Kinases - genetics; Proteins - genetics; Proteins - metabolism; Spermatids - metabolism; Transcription Initiation Site; X Chromosome - genetics; Y Chromosome - genetics
• ISSN: 0737-4038; 1537-1719
• DOI: 10.1093/molbev/msaa175

Abstract Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs, which have been coamplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict in which each favors its own transmission, resulting in sex ratio distortion of the progeny when Slx/Slxl1 versus Sly copy number is unbalanced. They are specifically expressed in male postmeiotic gametes (spermatids) and have opposite effects on gene expression: Sly knockdown leads to the upregulation of hundreds of spermatid-expressed genes, whereas Slx/Slxl1-deficiency downregulates them. When both Slx/Slxl1 and Sly are knocked down, sex ratio distortion and gene deregulation are corrected. Slx/Slxl1 and Sly are, therefore, in competition but the molecular mechanism remains unknown. By comparing their chromatin-binding profiles and protein partners, we show that SLX/SLXL1 and SLY proteins compete for interaction with H3K4me3-reader SSTY1 (Spermiogenesis-specific-transcript-on-the-Y1) at the promoter of thousands of genes to drive their expression, and that the opposite effect they have on gene expression is mediated by different abilities to recruit SMRT/N-Cor transcriptional complex. Their target genes are predominantly spermatid-specific multicopy genes encoded by the sex chromosomes and the autosomal Speer/Takusan. Many of them have coamplified with not only Slx/Slxl1/Sly but also Ssty during muroid rodent evolution. Overall, we identify Ssty as a key element of the X versus Y intragenomic conflict, which may have influenced gene content and hybrid sterility beyond Mus lineage since Ssty amplification on the Y predated that of Slx/Slxl1/Sly.