Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster

Abstract

The regulatory architecture of gene expression is known to differ substantially between sexes in Drosophila, but most studies performed so far used whole-body data and only single crosses, which may have limited their scope to detect patterns that are robust across tissues and biological replicates. Here, we use allele-specific gene expression of parental and reciprocal hybrid crosses between 6 Drosophila melanogaster inbred lines to quantify cis- and trans-regulatory variation in heads and gonads of both sexes separately across 3 replicate crosses. Our results suggest that female and male heads, as well as ovaries, have a similar regulatory architecture. On the other hand, testes display more and substantially different cis-regulatory effects, suggesting that sex differences in the regulatory architecture that have been previously observed may largely derive from testis-specific effects. We also examine the difference in cis-regulatory variation of genes across different levels of sex bias in gonads and heads. Consistent with the idea that intersex correlations constrain expression and can lead to sexual antagonism, we find more cis variation in unbiased and moderately biased genes in heads. In ovaries, reduced cis variation is observed for male-biased genes, suggesting that cis variants acting on these genes in males do not lead to changes in ovary expression. Finally, we examine the dominance patterns of gene expression and find that sex- and tissue-specific patterns of inheritance as well as trans-regulatory variation are highly variable across biological crosses, although these were performed in highly controlled experimental conditions. This highlights the importance of using various genetic backgrounds to infer generalizable patterns.

Cis-regulatory variation in relation to sex and sexual dimorphism inDrosophila melanogaster

“…These values are considerably higher than the values (6-17%) reported by Puixeu et al (2023). The greater divergence of haplotypes used in our study may have contributed to this difference; we crossed fly lines from different continents whereas they crossed lines from within a single population.…”

“…Based on population genetic analyses of human and fly data, Cheng & Kirkpatrick (2016) concluded that sexual conflict is the most intense in moderately sex-biased genes; this may lead one to predict cisregulatory variation being most common in genes with an intermediate sex bias. Two previous studies of cis-regulatory variation in D. melanogaster found different patterns from one another and neither matched this prediction (Osada et al 2017;Puixeu et al 2023).…”

“…Similarly, unbiased genes could either lack sexual conflict entirely or simply lack the appropriate variation to evolve sex-biased expression to mitigate conflict (Parsch and Ellegren 2013).Based on population genetic analyses of human and fly data, Cheng & Kirkpatrick (2016) concluded that sexual conflict is the most intense in moderately sex-biased genes; this may lead one to predict cisregulatory variation being most common in genes with an intermediate sex bias. Two previous studies of cis-regulatory variation in D. melanogaster found different patterns from one another and neither matched this prediction (Osada et al 2017;Puixeu et al 2023).Regulatory variants that affect expression similarly in both sexes would not allow for the resolution of sexual conflict via sex-biased gene expression. Thus, our second goal is to examine the extent to which cis-regulatory effects differ between the sexes, measured as 'sex-dependent' allelic imbalance.…”

“…In heads and whole body samples, there is an enrichment of cis-regulatory variants in female-biased genes. Osada et al (2017) and Puixeu et al (2023) also examined cis-regulatory variation in relation to sex bias. Some of the patterns reported in those two studies appear similar while others appear different from ours or from each other.…”

“…Parental effects on allele-specific gene expression in Drosophila are believed to be rare (Wittkopp et al 2006;Coolon et al 2012;Puixeu et al 2023). Still, certain forms of mapping bias could manifest as apparent parental effects.…”