Genetic architecture and sex-specific selection govern modular, male-biased evolution of <i>doublesex</i>.

Abstract

<i>doublesex</i> regulates early embryonic sex differentiation in holometabolous insects, along with the development of species-, sex-, and morph-specific adaptations during pupal stages. How does a highly conserved gene with a critical developmental role also remain functionally dynamic enough to gain ecologically important adaptations that are divergent in sister species? We analyzed patterns of exon-level molecular evolution and protein structural homology of <i>doublesex</i> from 145 species of four insect orders representing 350 million years of divergence. This analysis revealed that evolution of <i>doublesex</i> was governed by a modular architecture: Functional domains and female-specific regions were highly conserved, whereas male-specific sequences and protein structures evolved up to thousand-fold faster, with sites under pervasive and/or episodic positive selection. This pattern of sex bias was reversed in Hymenoptera. Thus, highly conserved yet dynamic master regulators such as <i>doublesex</i> may partition specific conserved and novel functions in different genic modules at deep evolutionary time scales.