Evidence for a sexual dimorphism in gene expression noise in metazoan species

Abstract

Many biological processes depend on very few copies of intervening elements, which makes such processes particularly susceptible to the stochastic fluctuations of these elements. The intrinsic stochasticity of certain processes is propagated across biological levels, causing genotype- and environment-independent biological variation which might permit populations to better cope with variable environments. Biological variations of stochastic nature might also allow the accumulation of variations at the genetic level that are hidden from natural selection, which might have a great potential for population diversification. The study of any mechanism that resulted in the modulation of stochastic variation is, therefore, of potentially wide interest. I propose that sex might be an important modulator of the stochastic variation in gene expression, i.e., gene expression noise. Based on known associations between different patterns of gene expression variation, I hypothesize that in metazoans the gene expression noise might be generally larger in heterogametic than in homogametic individuals. I directly tested this hypothesis by comparing putative genotype- and environment-independent variations in gene expression between females and males of Drosophila melanogaster strains. Also, considering the potential effect of the propagation of gene expression noise across biological levels, I indirectly tested the existence of a metazoan sexual dimorphism in gene expression noise by analyzing putative genotype- and environment-independent variation in phenotypes related to interaction with the environment in D. melanogaster strains and metazoan species. The results of these analyses are consistent with the hypothesis that gene expression is generally noisier in heterogametic than in homogametic individuals. Further analyses and discussion of existing literature permits the speculation that the sexual dimorphism in gene expression noise is ultimately based on the nuclear dynamics in gametogenesis and very early embryogenesis of sex-specific chromosomes, i.e., Y and W chromosomes.

Keywords: Gene expression noise; Genomic tuning knobs; Heterochromatin; Sex; Sex-specific chromosomes.

Figure 1. A sexual dimorphism in gene expression noise could explain differences in conditional response and divergence for sex-biased gene expression.

Charts symbolize gene expression dynamics for three transcripts in a population under different conditions or along time, under the assumption that gene expression is generally noisier in the heterogametic sex than in the homogametic sex: (A) Dynamics for a transcript that is overexpressed in the generally noisier heterogametic sex (Hm < Ht). (B) Dynamics for a transcript that is overexpressed in the generally less noisy homogametic sex (Hm > Ht). (C) Dynamics for a transcript equally expressed in both sexes (Hm ≈ Ht). Each line represents transcript abundance variation for a single individual in the population. Black and red lines represent variation in gene expression of stochastic or genetic nature, respectively. Grey areas represent gene expression levels with detrimental effects. In this case, both overexpression and underexpression beyond certain levels are detrimental. Individuals with detrimental expression stop contributing to the population. Noisier gene expression increases endurance for environmental changes, symbolized with narrower ranges for detrimental expression. Genetic variation in gene expression is prone to accumulate for transcripts that are overexpressed in the noisiest sex, as their phenotypes are often indistinguishable from the noise-driven phenotypic spectrum (A). Genetic variation in gene expression is less prone to accumulate for transcripts that are overexpressed in the less noisy sex or equally expressed in both sexes, as their phenotypes are often distinguishable from the noise-driven phenotypic spectrum, and removed from the population if detrimental (B and C).

Figure 2. Direct evidence for the existence of a sexual dimorphism in gene expression noise in D. melanogaster.

Distribution of measures for per transcript gene expression noise sex bias before and after randomly rearranging observed gene expression noise measures for D. melanogaster strains with SIM/REV genotype according to the dataset of Diaz-Castillo, Xia & Ranz (2012). Gene expression noise is measured as transcript abundance coefficient of variation in females and males (CV_F and CV_M). Sexual dimorphism in gene expression noise for the whole transcriptome before and after randomly rearranging the observed data was measured using W (see main text for further details). The negative skew of the distribution of observed data is consistent with the hypothesis that gene expression is generally noisier in males than in females.

Figure 3. Sexual dimorphism in gene expression noise for genes in five different compartments of the D. melanogaster genome.

The graph represents measures of sexual dimorphism in gene expression noise for loci with different chromatin structure and/or subnuclear localization according to Filion et al. (2010), in D. melanogaster strains and genotypes represented in the dataset of Diaz-Castillo, Xia & Ranz (2012). BLUE and GREEN components represent known heterochromatin repositories (Filion et al., 2010). BLACK and RED are enriched in loci with tissue-restricted gene expression and lamin-binding targets, suggesting they might be located towards the repressive environment of the nuclear periphery (Filion et al., 2010). YELLOW is the only component associated with broadly expressed loci (Filion et al., 2010). Sexual dimorphism in gene expression noise was measured using W (see main text for further details). The area of the graph representing W for BLUE, RED, and GREEN loci is amplified in the inner box.

Figure 4. Genomic tuning knob-sink effect of Y chromosomes.

Model for the assortment of heterochromatin-forming elements in homogametic and heterogametic nuclei, under the assumption that heterochromatic-forming elements are found in similar and limiting amounts in all nuclei. Font size is used to symbolize differences in the repetitive DNA content of sexual chromosomes, i.e., X and Y, and autosomes (A). The fraction of heterochromatin-forming elements deployed in Y chromosomes can vary depending on their content in repetitive DNA. The assortment of heterochromatin-forming elements in non-Y loci would be very different if the nuclei carry or lack Y chromosomes, i.e., XYAA or XXAA, and slightly different if the Y chromosomes have different amounts of repetitive DNA. Slight differences in chromatin compaction across the genome ultimately based in small differences in Y chromosome repetitive DNA will cause an increase in gene expression noise across the genome, whereas higher level of chromatin compaction in non-Y heterochromatic loci in XXAA nuclei will be translated into less extreme male-biased gene expression noise in these loci (Fig. 3, and main text).