Recent Cis-Trans Coevolution Driven by the Emergence of A Novel Gene in Drosophila

Young, or newly evolved, genes arise ubiquitously across the tree of life, and can rapidly acquire novel functions that influence a diverse array of biological processes1. Previous work identified a young regulatory gene in Drosophila, Zeus, which diverged rapidly from its parent Caf40 and took on roles in the male reproductive system. This neofunctionalization was accompanied by differential binding of the Zeus protein to loci throughout the Drosophila melanogaster genome2. However, the way in which new DNA-binding proteins acquire and coevolve with their targets in the genome is not understood. Here, by comparing Zeus ChIP-seq data from D. melanogaster and D. simulans to the ancestral Caf40 binding events from D. yakuba, a species that diverged before the duplication event, we find a dynamic pattern in which Zeus binding rapidly co-evolved with a previously unknown DNA motif under the influence of positive selection. Interestingly, while both copies of Zeus acquired targets at male-biased and testis-specific genes, D. melanogaster and D. simulans proteins have specialized binding on different chromosomes, a pattern echoed in the evolution of the associated motif. Our results suggest that evolution of young regulatory genes can be coupled to substantial rewiring of the transcriptional networks into which they integrate, even over short evolutionary timescales. Our results thus uncover dynamic, genome-wide evolutionary processes associated with new genes.