Sex-Biased Gene Expression and Evolution of the X Chromosome in Nematodes

Abstract

Studies of X chromosome evolution in various organisms have indicated that sex-biased genes are nonrandomly distributed between the X and autosomes. Here, to extend these studies to nematodes, we annotated and analyzed X chromosome gene content in four Caenorhabditis species and in Pristionchus pacificus. Our gene expression analyses comparing young adult male and female mRNAseq data indicate that, in general, nematode X chromosomes are enriched for genes with high female-biased expression and depleted of genes with high male-biased expression. Genes with low sex-biased expression do not show the same trend of X chromosome enrichment and depletion. Combined with the observation that highly sex-biased genes are primarily expressed in the gonad, differential distribution of sex-biased genes reflects differences in evolutionary pressures linked to tissue-specific regulation of X chromosome transcription. Our data also indicate that X dosage imbalance between males (XO) and females (XX) is influential in shaping both expression and gene content of the X chromosome. Predicted upregulation of the single male X to match autosomal transcription (Ohno's hypothesis) is supported by our observation that overall transcript levels from the X and autosomes are similar for highly expressed genes. However, comparison of differentially located one-to-one orthologs between C. elegans and P. pacificus indicates lower expression of X-linked orthologs, arguing against X upregulation. These contradicting observations may be reconciled if X upregulation is not a global mechanism but instead acts locally on a subset of tissues and X-linked genes that are dosage sensitive. IN an XY sex-determination system, male and female genomes are identical with the exception of the male-specific Y chromosome, which bears few genes (Charlesworth et al. 2005). This is particularly true when the Y chromosome is thought to be completely lost, as is the case for C. elegans and many other nematodes (Walton 1940). Because gene content is the same, phenotypic differences between males and females, termed "sexual dimorphisms," must be caused by differential gene expression between the two sexes (Connallon and Knowles 2005;Ellegren and Parsch 2007). Throughout the article, such differentially expressed genes are referred to as "sex biased." As males and females have different fitness optima, a trait that is beneficial to one sex can be harmful to the other (termed sexual antagonism) (Rice and Chippindale 2001;Arnqvist 2004;Connallon and Knowles 2005;Ellegren and Parsch 2007;Mank et al. 2008a;Rice 1984). The evolution of sex-biased gene expression is thought to mediate the effects of sexual antagonism and allow for achievement of sex-specific fitness. Previous studies have indicated that anywhere between 30 and 60% of metazoan genes may be sex biased Parisi et al. 2004;Reinke et al. 2004;Yang et al. 2006;Reinius et al. 2008;Small et al. 2009;Innocenti and Morrow 2010;Assis et al. 2012;Reinius et al. 2012;Thomas et al. 2012). Genes with sex-biased exp...

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

“…Consistent with this, transcriptional profiling in C. elegans revealed a significant underrepresentation of meiosis and sperm-expressed genes on the X (Reinke et al 2000). It is likely that this underrepresentation of meiosis and spermatogenesis genes is also true of the Caenorhabditis group as a whole as there is a high degree of synteny between the X chromosomes in those species with good genomic assemblies (Hillier et al 2007;Fierst et al 2015) and expression analyses have uncovered a depletion of malebiased expressed genes on the X chromosome of C. briggsae, C. remanei, C. brenneri, as well as the more distantly related Pristionchus pacificus (Albritton et al 2014).…”

Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

“…Previous studies indicate up to 60% of all genes show sex-biased expression [in mice (Khil et al 2004;Yang et al 2006;Reinius et al 2012), flies (Parisi et al 2003;Ranz et al 2003;Allen et al 2013;Kaiser and Bachtrog 2014), and nematodes (Reinke et al 2004;Thomas et al 2012;Albritton et al 2014)]. Previous genome-wide studies found that compared to autosomes, the X chromosome generally harbors more genes with female-biased expression and fewer genes with malebiased expression [in mice (Khil et al 2004;Yang et al 2006;Reinius et al 2012), flies (Parisi et al 2003;Ranz et al 2003), and nematodes (Reinke et al 2004;Thomas et al 2012;Albritton et al 2014)]. However, this observed enrichment of female bias and depletion of male bias from the X is a generalization that may not apply universally to every tissue type or developmental stage.…”

“…Similar results were observed using expression cutoffs of 0.1 FPKMs and 10 FPKMs to determine expressed genes ( Figure S1). Compared to adults (Thomas et al 2012;Albritton et al 2014), there were fewer genes showing sex-biased expression in L3 larvae (Figure 2A). This result is expected, as most sexually dimorphic tissues develop after the L3 stage (Kimble and Hirsh 1979).…”

“…The contribution of X chromosome dose to sex-biased expression was also small ( Figure 2C). We grouped genes into sex-specific, high sex-biased, low-sex biased, and nonbiased expression categories with the same cutoffs from our previous work (Albritton et al 2014; see Materials and Methods). Consistent with the observation that the X chromosome is dosage compensated extensively in L3 larvae (Kramer et al 2015), genes with sex-biased expression were distributed similarly between the X and autosomes ( Figure 2D).…”

“…Another way to mitigate the effect of X chromosome number difference between sexes is to reduce the need to dosage compensate. Indeed, C. elegans X chromosome is depleted of predicted dosage-sensitive genes, such as the haploinsufficient genes and genes that encode for subunits of protein complexes (Albritton et al 2014;Kramer et al 2015).X chromosome copy number contributes to sex-biased gene expression in the germline and in early embryogenesisWe found that in young adults, X chromosome copy number difference between the sexes increases the number of genes that show low hermaphrodite-biased expression and reduces the number of genes that show low male-biased expression on the X (Figure 5F). Contribution of X dose to hermaphroditebiased expression in the absence of the DCC is seen in the germline ( Figure 6B).…”