体の左右反転を引き起こす遺伝子を推定 ―日本のカタツムリを用いたアプローチ―

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 do not ordinarily vary in the direction of their asymmetry. Snails are an exception because some wild-living species show abundant variation—externally visible in the shell coiling direction or “chirality”—yet the existing knowledge is from species, including the pond snail Lymnaea stagnalis, in which the sinistral mutation is rare and causes pathology. Here, we show that chiral polymorphism in Japanese Euhadra snails is due to functional variation in an unconventional myosin I a/b, a myosin family member 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 associated with pathology. Analyses show that relaxed selection enabled dominant-acting amino acid substitutions in the sinistral version of the Euhadra myosin motor domain and motor-lever junction, potentially affecting actomyosin interactions. For comparison, in the pond snail, we found that thousands of genes are differentially expressed between dextral and sinistral embryos due to the frameshift mutation in a formin gene. Overall, these results reinforce the role of myosin and actin-driven processes in LR symmetry breaking, broaden the known molecular repertoire, and highlight key mutations and positions in myosins that should be explored further, including in other animals.