Y not a dead end: epistatic interactions between Y-linked regulatory polymorphisms and genetic background affect global gene expression in Drosophila melanogaster

Abstract

The Y chromosome, inherited without meiotic recombination from father to son, carries relatively few genes in most species. This is consistent with predictions from evolutionary theory that nonrecombining chromosomes lack variation and degenerate rapidly. However, recent work has suggested a dynamic role for the Y chromosome in gene regulation, a finding with important implications for spermatogenesis and male fitness. We studied Y chromosomes from two populations of Drosophila melanogaster that had previously been shown to have major effects on the thermal tolerance of spermatogenesis. We show that these Y chromosomes differentially modify the expression of hundreds of autosomal and X-linked genes. Genes showing Y-linked regulatory variation (YRV) also show an association with immune response and pheromone detection. Indeed, genes located proximal to the euchromatin-heterochromatin boundary of the X chromosome appear particularly responsive to Y-linked variation, including a substantial number of odorant-binding genes. Furthermore, the data show significant regulatory interactions between the Y chromosome and the genetic background of autosomes and X chromosome. Altogether, our findings support the view that interpopulation, Y-linked regulatory polymorphisms can differentially modulate the expression of many genes important to male fitness, and they also point to complex interactions between the Y chromosome and genetic background affecting global gene expression.

Figure 1.—

Solid bars represent the number of genes differentially expressed by males possessing Y_I or Y_F in an Indian genetic background (top), a French genetic background (middle), or a B4361 genetic background (bottom), as a function of the Bayesian posterior probability of differential expression. Shaded bars indicate the estimated number of genes expected by chance.

Figure 2.—

Venn diagrams showing the number of unique Y-regulated genes (Bayesian posterior probability >0.95) in Indian (I), French (F), and B4361 genetic backgrounds and overlap between affected genes in different backgrounds. The number of genes found to be significant in each individual background is given in parentheses.

Figure 3.—

Clustering of genes showing YRV along the euchromatic portion of the X chromosome in an Indian genetic background (top), a French genetic background (middle), or a B4361 genetic background (bottom). Solid lines indicate observed density of genes around a 2-Mb sliding window (step size 1 Mb). Shaded lines indicate 95% confidence intervals. A schematic X chromosome is drawn at the top left with the shaded area representing euchromatin and the solid area representing heterochromatin. The solid knob at the right represents the X chromosome centromere. Columns represent genes for which males possessing Y_F showed enhanced expression over males possessing Y_I (Y_F > Y_I) or vice versa (Y_I > Y_F). An asterisk denotes a chromosomal segment containing significantly more genes showing Y-linked regulation than expected by chance.

Figure 4.—

Relative expression levels of three genes showing YRV in Y_F males vs. Y_I males in three genetic backgrounds (I, Indian; F, French; and B4361). Expression levels are shown as the ratio of Y_F over Y_I expression (±SE). Obp19a is an odorant-binding-protein gene near the X euchromatin–heterochromatin boundary. Drosocin (Dro) is an immune-response gene. Pbprp3 encodes pheromone-binding protein-related protein 3, a pheromone-binding protein.

Figure 5.—

Gene expression profiles generated by k-means clustering. Each line represents the expression of one gene across each background-by-Y group. Expression measures were standardized across groups and analyzed using k-means cluster analysis. There are 19, 88, and 93 genes in clusters 1, 2, and 3, respectively.

Figure 6.—

Y-chromosome effects on position-effect variegation (PEV). Y_I suppresses PEV more and thus allows more expression of w[m4h] than Y_F in all three genetic backgrounds (I, Indian; F, French; and B4361). Eye pigmentation was measured as absorption of light at 480 nm. Pictures of heads of representative male flies are shown to the right.