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

Abstract

Much of sexual dimorphism is likely due to sex-biased gene expression, which results from differential regulation of a genome that is largely shared between males and females. Here we use allele-specific expression to explore cis-regulatory variation in Drosophila melanogaster in relation to sex. We test for sex differences in cis-regulatory effects as well as examine patterns of cis-regulatory with respect to two other levels of variation in sexual dimorphism: (i) across genes varying in their degree of sex-biased expression, and (ii) among tissues that vary in their degree of dimorphism (e.g., relatively low dimorphism in heads vs high dimorphism in gonads). We uncover evidence of widespread cis-regulatory variation in all tissues examined, with female-biased genes being especially enriched for said variation. A sizeable proportion of cis-regulatory variation is observed to have sex-specific effects, with sex-dependent cis effects being more frequent in gonads than in heads. Finally, we detect some genes with reversed allelic imbalance between the sexes. Such variants could provide a mechanism for sex-specific dominance reversals, a phenomenon important for sexually antagonistic balancing selection.

Sex-specific Dominance and Its Effects on Allelic Diversity in Sexually Antagonistic Loci

“…Pronounced sexual dimorphism in gene expression is near ubiquitous in gonochorists and both theory (Connallon and Knowles, 2005; Rowe et al, 2018; Tosto et al, 2023) and empirical data (Innocenti and Morrow, 2010; Hollis et al, 2014; Wong and Holman, 2023) suggest that regions affecting gene expression are often under, or have at least experienced a history of, SA selection. Moreover, several recent studies have documented widespread sex-specific dominance in gene expression (Puixeu et al, 2023; Mishra et al, 2022; Kaufmann et al, 2024), suggesting that regulatory regions may be enriched with loci showing segregating SA genetic variation. Several genomic regions with putative regulatory functions, such as mini- and microsatellites, show pronounced PAP and sometimes appear to be under balancing SA selection (e.g., Lonn et al, 2017).…”

“…Although dominance reversal for fitness is indeed predicted under curved fitness landscapes (Fry, 2010; Manna et al, 2011; Connallon and Chenoweth, 2019), most documented cases of sex-specific dominance involve dominance effects on phenotypes. This is true for age at maturation in salmon (Barson et al, 2015), morphology in water striders (Fairbairn et al, 2023), immune function in fruit flies (Geeta Arun et al, 2021), migratory behaviour in rainbow trout (Pearse et al, 2019) and transcript abundance in fruit flies (Puixeu et al, 2023; Mishra et al, 2022) and beetles (Kaufmann et al, 2024). This suggests that documented cases of sex-specific dominance for fitness components (Grieshop and Arnqvist, 2018; Mérot et al, 2020) may to a large extent emerge from underlying differences in dominance for trait expression, which we believe substantiates our approach.…”

Dominance reversals: the resolution of genetic conflict and maintenance of genetic variation

“…The 'dominance modifier' a i cannot act alone and relies on the surrounding regulatory network, and 4. Our focal polymorphism exhibited a pattern of reversed allele-specific expression between the sexes (electronic supplementary material, figure S2.6)a detectable signature of dominance reversal [78].…”

“…They found a negative genetic correlation between the male and female dominance ordination among strains, implying that strains' fixed genetic variation tended to be dominant to that of other strains in one sex but recessive to that of other strains when measured in the opposite sex, a polygenic signal of sex-specific dominance reversal for fitness [52]. Mishra et al's [78] recent study of allele-specific expression in D. melanogaster also identified evidence of polygenic sex-specific dominance reversal. In 176 of 3796 quality-controlled genes, opposite alleles were significantly more highly expressed in opposite sexes (with as many as 26/176 representing false positives) [78].…”

“…Allowing these gene regulatory networks to evolve in forward-time individual-based population genetic simulations (electronic supplementary material S2) revealed that: Selection favours the adaptive aiAi haplotypes that enable heterozygous males and females to plastically adjust the [ B ] toward their sex-specific fitness optima (electronic supplementary material, figure S2.4) because it partially resolves the genetic conflict (electronic supplementary material, figure S2.5),This dominance reversal in turn tends to maintain the focal sexually antagonistic polymorphism (electronic supplementary material, figure S2.2),The ‘dominance modifier’ αi cannot act alone and relies on the surrounding regulatory network, andOur focal polymorphism exhibited a pattern of reversed allele-specific expression between the sexes (electronic supplementary material, figure S2.6) – a detectable signature of dominance reversal [78]. …”