Epigenetic effects of polymorphic Y chromosomes modulate chromatin components, immune response, and sexual conflict

Abstract

Genetic conflicts between sexes and generations provide a foundation for understanding the functional evolution of sex chromosomes and sexually dimorphic phenotypes. Y chromosomes of Drosophila contain multi-megabase stretches of satellite DNA repeats and a handful of protein-coding genes that are monomorphic within species. Nevertheless, polymorphic variation in heterochromatic Y chromosomes of Drosophila result in genome-wide gene expression variation. Here we show that such naturally occurring Y-linked regulatory variation (YRV) can be detected in somatic tissues and contributes to the epigenetic balance of heterochromatin/euchromatin at three distinct loci showing position-effect variegation (PEV). Moreover, polymorphic Y chromosomes differentially affect the expression of thousands of genes in XXY female genotypes in which Y-linked protein-coding genes are not transcribed. The data show a disproportionate influence of YRV on the variable expression of genes whose protein products localize to the nucleus, have nucleic-acid binding activity, and are involved in transcription, chromosome organization, and chromatin assembly. These include key components such as HP1, Trithorax-like (GAGA factor), Su(var)3-9, Brahma, MCM2, ORC2, and inner centromere protein. Furthermore, mitochondria-related genes, immune response genes, and transposable elements are also disproportionally affected by Y chromosome polymorphism. These functional clusterings may arise as a consequence of the involvement of Y-linked heterochromatin in the origin and resolution of genetic conflicts between males and females. Taken together, our results indicate that Y chromosome heterochromatin serves as a major source of epigenetic variation in natural populations that interacts with chromatin components to modulate the expression of biologically relevant phenotypic variation.

Fig. 1.

Epigenetic contributions of polymorphic Y chromosomes to global chromatin regulation in somatic tissues. (A) Variation in eye pigmentation in stocks carrying the X chromosome marker w[m4h] and Y chromosomes sampled from diverse localities worldwide. (B) Eye phenotypes showing differential variegated expression for w[m4h] in four Y chromosome backgrounds. These flies are genetically identical except for the origin of the Y chromosome. (C) Differential variegation between Y[Congo] and Y[Ohio] strains for the X-linked marker w[m4h] and second chromosome markers bw[D] and lt[x13].

Fig. 2.

Polymorphic Y chromosomes modulate the expression of chromatin components. (A) Heat map of relative expression levels of 101 differentially expressed genes (P < 0.01) belonging to the Gene Ontology category of chromatin silencing. (B) Examples of key chromatin components expressed to a lesser degree in XXY[Congo] (red) relative to XXY[Ohio] (green). Bars denote 95% credible intervals. Relative expression levels are shown, with the lowest expression normalized to 1 (red).

Fig. 3.

Polymorphic Y chromosomes modulate the expression of mitochondria-related and immune-related genes. (A and B) Heat maps of relative expression levels of 65 differentially expressed genes (P < 0.01) belonging to the Gene Ontology category of electron transport (A) and 52 differentially expressed genes (P < 0.01) belonging to the Gene Ontology categories of defense response and immunity (B). (C and D) Examples of mitochondria-related genes (C) and immune-related genes (D) more highly expressed in XXY[Congo] (green) relative to XXY[Ohio] (red). Bars denote 95% credible intervals. Relative expression levels are shown, with the lowest expression normalized to 1 (red).

Fig. 4.

The autosomes from Congo and Ohio do not harbor dominant modifiers of Y chromosome-driven PEV. Eye phenotypes showing variegated expression for w[m4h] in Y[Congo] and Y[Ohio] in three backgrounds of autosomes (Congo, Ohio, and laboratory). Autosomes from Congo or Ohio are heterozygous, with a common set of autosomes inherited from a laboratory strain (+) carrying the X-linked w[m4h] marker.