Sexual Dimorphism through the Lens of Genome Manipulation, Forward Genetics, and Spatiotemporal Sequencing

Sexual reproduction often leads to selection that favors the evolution of sex-limited traits or sex-specific variation for shared traits. These sexual dimorphisms manifest due to sex-specific genetic architectures and sex-biased gene expression across development, yet the molecular mechanisms underlying these patterns are largely unknown. The first step is to understand how sexual dimorphisms arise across the genotype-phenotype-fitness map. The emergence of "4D genome technologies" allows for efficient, high-throughput, and cost-effective manipulation and observations of this process. Studies of sexual dimorphism will benefit from combining these technological advances (e.g., precision genome editing, inducible transgenic systems, and single-cell RNA sequencing) with clever experiments inspired by classic designs (e.g., bulked segregant analysis, experimental evolution, and pedigree tracing). This perspective poses a synthetic view of how manipulative approaches coupled with cutting-edge observational methods and evolutionary theory are poised to uncover the molecular genetic basis of sexual dimorphism with unprecedented resolution. We outline hypothesis-driven experimental paradigms for identifying genetic mechanisms of sexual dimorphism among tissues, across development, and over evolutionary time.