The Ancestral Cuticle Suppresses .

Genetic background commonly modifies the effects of mutations. We discovered that worms mutant for the canonical gene, identified by Brenner in 1974, do not roll in the genetic background of the wild strain CB4856. Using linkage mapping, association analysis and gene editing, we determined that N2 carries an insertion in the collagen gene that acts as a recessive enhancer of rolling. From population and comparative genomics, we infer the insertion is derived in N2 and related laboratory lines, likely arising during the domestication of , and breaking a conserved protein. The ancestral version of also modifies the phenotypes of four other classical cuticle mutant alleles, and the effects of natural genetic variation on worm shape and locomotion. These results underscore the importance of genetic background and the serendipity of Brenner's choice of strain.