Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

Two people with the same disease, or who inherit the same genetic mutation, often show different symptoms or respond to medical treatments in different ways. This is because many traits are not the result of a single gene, but of several genes interacting with each other in complex ways to form networks that lead to many possible outcomes. Gene regulatory networks, which control how animals develop, change over evolutionary time to create the vast variety of different species that exist today. However, it is still unclear how mutations in these networks can occur without negatively impacting their activity, or how networks become rewired during evolution. To address these questions, Torres Cleuren et al. studied the gene regulatory network that controls the development of the gut across approximately 100 different strains of Caenorhabditis elegans, a widely studied nematode worm. This involved testing how switching off particular genes affected gut development in embryos of the worm. The experiments revealed that the first steps in the gene regulatory networks that control gut development vary drastically between the different wild strains of C. elegans. For example, in some of the strains, two genes known as skn-1 and mom-2 are essential for gut formation, whereas in others the gut often forms even when these genes are switched off. These results support the idea that some of the genes in the network can compensate for loss of others, explaining how mutations can accumulate without impacting the development of the embryo. The findings of Torres Cleuren et al. provide important insights into how gene regulatory networks can be rewired, with some components accumulating mutations and acquiring new roles, while others stay the same.