Orthologs of the C. elegans heterochronic genes have divergent functions in C. briggsae

The heterochronic genes of C. elegans comprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway and the significance of the relationships among its components, we characterized 11 C. briggsae orthologs of C. elegans heterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those of C. elegans . Although most mutant orthologs displayed defects in developmental timing, their phenotypes could differ in which stages were affected, the penetrance and expressivity of the phenotypes, or by having additional pleiotropies that were not obviously connected to developmental timing. However, when examining pairwise epistasis and synergistic relationships, we found those paralleled the known relationships between their C. elegans orthologs, suggesting that the arrangements of these genes in functional modules is conserved, but the modules’ relationships to each other and/or to their targets has drifted since the time of the species’ last common ancestor. Furthermore, our investigation has revealed a relationship to this pathway to other aspects of the animal’s growth and development, including gonad development, that is relevant to both species.