Size variation is regulated differently between and within sexes in natural populations

Size of organs/organisms is a polygenic trait. Many of the growth-regulatory genes constitute conserved growth signaling pathways. However, how these genes are genetically orchestrated at the systems level to attain the observed natural variation in size including sexual size dimorphism is mostly unknown. Here we take a systems approach employing transcriptome-wide association studies (TWAS) on the Drosophila wing. We show that expression levels of many critical growth regulators such as Wnt and TGFß pathway components significantly differ between sexes but not between lines exhibiting size differences within each sex, suggesting a primary role of these regulators in sexual size dimorphism. In contrast, we find that between-line size variation is regulated by genes that have never been implicated in growth. In addition, we show that expression quantitative trait loci (eQTLs) linked to the novel growth regulators accurately predict population-wide, between-line wing size variation. In summary, our study unveils differential gene regulatory systems that control wing size variation between and within sexes.