An ancient polymorphism in myosin I a/b determines the left-right asymmetry of Japanese snails

Left-right (LR) asymmetry is a fundamental feature of animal development, yet progress in understanding its establishment has been limited by the fact that almost all animals exhibit invariant chirality. Snails are the exception because some wild-living species show abundant chiral variation, yet the existing knowledge is from snails in which the chirality mutation is rare and causes pathology. Here, we show that a chiral polymorphism in Japanese Euhadra snails is due to functional variation in an unconventional myosin I a/b, an isoform not previously implicated in LR specification in any animal. Both the sinistral and dextral gene variants are ancient, impart minimal transcriptional differences in the single-cell embryo and are not pathological. Phylogenetic and structural modelling suggests that dominant-acting amino acid substitutions in the myosin actin-binding domain and/or motor-level junction were enabled by relaxed selection. These results broaden the known molecular repertoire underlying LR asymmetry, suggest key mutations and positions that should be explored in other model animals, and highlight snails as a powerful model for understanding the origins of animal LR asymmetry.