A Developmental Switch Generating Phenotypic Plasticity Is Part of a Conserved Multi-gene Locus

Summary Switching between alternative complex phenotypes is often regulated by "supergenes," polymorphic clusters of linked genes such as in butterfly mimicry. In contrast, phenotypic plasticity results in alternative complex phenotypes controlled by environmental influences rather than polymorphisms. Here, we show that the developmental switch gene regulating predatory versus non-predatory mouth-form plasticity in the nematode Pristionchus pacificus is part of a multi-gene locus containing two sulfatases and two α-N-acetylglucosaminidases ( nag ). We provide functional characterization of all four genes, using CRISPR-Cas9-based reverse genetics, and show that nag genes and the previously identified eud-1 /sulfatase have opposing influences. Members of the multi-gene locus show non-overlapping neuronal expression and epistatic relationships. The locus architecture is conserved in the entire genus Pristionchus . Interestingly, divergence between paralogs is counteracted by gene conversion, as inferred from phylogenies and genotypes of CRISPR-Cas9-induced mutants. Thus, we found that physical linkage accompanies regulatory linkage between switch genes controlling plasticity in P. pacificus .