Sex biased expression and co-expression networks in development, using the hymenopteran Nasonia vitripennis

Abstract

Sexual dimorphism requires gene expression regulation in developing organisms. Differential expression, alternative splicing and transcript-transcript interactions all contribute to developmental differences between the sexes. However, few studies have described how these processes change across developmental stages, or how they interact to form co-expression networks. We compare the dynamics of all three regulatory processes in the sexual development of the model parasitoid wasp Nasonia vitripennis, a system that permits genome wide analysis of sex bias from early embryos to adults. We find relatively little sex-bias in embryos and larvae at the whole-gene level, but several sub-networks show sex-biased transcript-transcript interactions in early developmental stages. These provide new candidates for hymenopteran sex determination, including histone modification genes. In contrast, sex-bias in pupae and adults is driven by wholegene differential expression. We observe sex-biased splicing consistently across development, but mostly in genes that are already biased at the whole-gene level. Finally, we discover that sex-biased networks are enriched by genes specific to the Nasonia clade, and that those genes possess the topological properties of key regulators. These findings suggest that regulators in sex-biased networks evolve more rapidly than regulators of other developmental networks.(Chang et al. 2011; Innocenti and Morrow 2010 but see Wang, Werren and Clark 2015). However, the focus on adult gene expression does not reveal sex differential processes during development, and several genes are sex-biased only during those early stages (Perry, Harrison, and Mank 2014;Mank et al. 2010;Zhao et al. 2011). Changes in sex-bias expression of the same gene across development are most likely to create conflict, since the same locus may be under selection for changes in female-specific and male-specific functions in different developmental stages -a scenario that we term 'developmental sexual conflict'. Several studies have also shown that alternative splicing can show sex-bias (Telonis-Scott et al. 2008;Hartmann et al. 2011; Brown et al. 2014), and that sex-biased splicing affects sex determination (Verhulst et al. 2013; Verhulst, Beukeboom, and van de Zande 2010) and sexual development (Chang et al. 2011).The co-expression of multiple genes can result in effects that are qualitatively and quantitatively different from the sum of the effects of each gene (Ament et al. 2012;Spitz and Furlong 2012;Boyle et al. 2014), and provides a largely unexplored mechanism for the regulation of sex-specific differences; the same group of genes can have identical expression levels in males and females, yet still cause a sex-specific effect if they are only co-expressed in one sex (Arnold, van Nas and Lusis 2009;). These interactions are therefore impossible to detect by independently testing transcripts, but can be identified via differential correlation analyses on transcriptional modules, or differential cluster correlations (Tesson...

Differential gene expression patterns during gametophyte development provide insights into sex differentiation in the dioicous kelp Saccharina japonica

“…In contrast to the results in S. japonica, in the isogamous brown alga Ectocarpus, less than 12% of the sex-biased genes were detected during haploid gametophyte generation, and more sex-biased genes were found in immature gametophytes than in fertile gametophytes; Ectocarpus exhibits low-level sexual dimorphism in gametophytes [8]. Sexbiased gene expression variation by developmental stage has been reported in many plants and animals in previous studies [24,47,48]. In this study, the phenotypic difference between the male and female gametophytes was only in the cell size in the immature stage.…”

“…In addition to SDR genes, many sexrelated genes are scattered throughout the genome, and their sex-biased expression is likely to account for most sexually dimorphic traits [23]. Herein, sex-biased gene expression is by far the most studied among the mechanisms that generate differences between sexes in invertebrates [24][25][26], vertebrates [27,28] and plants [29,30]. However, genome-wide patterns of sex-biased gene expression have not been identified and characterized in the kelp S. japonica thus far.…”

Dynamics of sex-biased gene expression during development in the stick insectTimema californicum

“…A similar shift from femaleto male-bias in gene expression during development was found in Nasonia jewel wasps, where little male-biased expression was detected until the pupal stage, during the activation of spermatogenesis. Similar to Timema, the shift was interpreted as a different developmental timing of the two sexes (Rago et al 2020). In Timema, malebiased genes were also expressed in a relatively stage-specific manner, in contrast to a more constant expression of female-biased genes.…”

“…This difference is clearest at the adult stage when most of the expressed genes in D. melanogaster were sex-biased (85%), compared to only 20% in T. californicum. Similar to Drosophila, other holometabolous insects also featured sex-bias for more than half of the genes expressed at the adult stage (Dean A Baker et al, 2011;Rago et al, 2020), while all studied hemimetabolous insects had a much smaller proportion of sex-biased genes (<10%) (Pal and Vicoso, 2015). Why there is such a difference in the prevalence of sex-biased genes between species with different developmental strategies is still an open question.…”

“…These distinct dynamics for the morphological differentiation of the sexes are expected to be mirrored by sex-biased gene expression, with abrupt versus gradual increases in the proportion of sex-biased genes over development. However, studies of sex-biased gene expression during development have thus far only been conducted in holometabolous insects, with the main focus on Drosophila (Ingleby et al, 2015;Magnusson et al, 2011;Perry et al, 2014;Rago et al, 2020), precluding comparisons between species with different developmental strategies.…”