View Program - 2022 Population, Evolutionary, and Quantitative Genetics Conference

There is a long history of strong trans- genetic effects caused by the Y chromosome. The Y is proposed to cause these effects by acting as a “heterochromatin sink,” competing with other regions of heterochromatin to sequester regulatory factors, like HP1a, that are in limited supply. The Drosophila melanogaster Y is composed entirely of constitutive heterochromatin; it contains only 16 protein coding genes and no sex-determination locus. Variation and dosage of the Drosophila Y are associated with genome-wide expression changes affecting male fertility, sex-specific aging, temperature adaptation of spermatogenesis, geotaxis, and immune response, but the mechanism is unknown. Brown and Bachtrog (2020) identified hundreds of changes in gene expression and the distribution of repressive histone marks (H3K9me2 and H3K9me3) associated with different numbers of Y chromosomes.

Here we further dissected the trans-effects of the Drosophila Y by examining the genomic distribution of Y-dosage-induced changes in gene expression and three-dimensional genome folding. We used RNA-seq to profile gene expression in males with zero, one, and two copies of the Y chromosome. To identify important trans effects that may have been masked by genetic background in previous studies, we used a reciprocal crossing scheme to control for effects caused by autosomal and X-linked differences between strains. We identified relevant expression changes through pairwise comparisons between males sharing X chromosome or autosomal backgrounds and using likelihood-ratio tests in a method similar to time series analysis, to compare all lines at once. We discovered a group of genes, mostly on the X, that are suppressed by the presence of one or more Ys. This group includes pira, a SUMO protease targeted by Y-linked piRNAs. Another group of autosomal genes had similar expression patterns to Y-linked genes. We performed High-throughput Chromosome Conformation Capture (Hi-C) to investigate how 3D folding of the genome is affected by Y-dosage. If 3D conformation contributes to trans effects of the Y, we expect to see a correlation between changes in gene expression and 3D interactions. Understanding trans interactions between the Y and the rest of the genome may clarify how heterochromatin regulates gene expression, with implications for the dynamics of Y chromosome evolution, the evolution of sexual dimorphism and sexual conflict, and the disease-related consequences of genome dysregulation.

Genome-wide Effects of the Y Chromosome on Gene Expression and Genome Architecture in Drosophila melanogaster