RT Journal Article SR Electronic T1 Sexual antagonism exerts evolutionarily persistent genomic constraints on sexual differentiation in Drosophila melanogaster JF bioRxiv FD Cold Spring Harbor Laboratory SP 117176 DO 10.1101/117176 A1 Mark S. Hill A1 Filip Ruzicka A1 Sara Fuentes A1 Julie M. Collet A1 Edward H. Morrow A1 Kevin Fowler A1 Max Reuter YR 2017 UL http://biorxiv.org/content/early/2017/03/15/117176.abstract AB The divergent reproductive roles of males and females favour different phenotypes1,2. However, responses to these selective pressures are constrained by a shared genome, leading to 'sexual antagonism' where different alleles at given loci are favoured in the two sexes1, 3-5. Sexual antagonism is taxonomically widespread and imposes an important evolutionary constraint on adaptation1,4. It also maintains genetic variation with sex-specific deleterious effects6,7, contributing to disease susceptibility in humans8,9. Yet, despite its prevalence and importance, we know virtually nothing about the evolutionary dynamics of sexually antagonistic variation10-12 or the general properties of the biological processes underlying antagonistic loci13. Here we report the first genomewide identification and characterisation of sexually antagonistic SNPs in a population of D. melanogaster. We identify 4,899 antagonistic SNPs, distributed in 1,462 local clusters across the genome. Contrary to longstanding predictions3, we show that these loci are significantly underrepresented on the X chromosome. Comparative analyses reveal that sexual antagonism exerts widespread and evolutionarily persistent constraints on the species’ genome. Thus, antagonistic loci generate a detectable signature of balancing selection in populations across the distribution range of D. melanogaster, and often segregate as extended haplotypes with homogeneous sex-specific fitness effects. In functional terms, we find that sexual antagonism is rooted in the regulation of development and associated primarily with cis-regulatory elements. We further detect multiple associations with the sexual differentiation cascade, including the gene fruitless, a major driver of neuronal and behavioural differentiation between males and females. This reveals that sexual antagonism resides at the core of sex-specific development. Collectively, these results provide unprecedented insights into the biology and evolution of sexual antagonism, and open opportunities for more detailed studies of constraints on sex-specific adaptation and mechanisms that resolve them.