An allozyme polymorphism is associated with a large chromosomal inversion in the marine snail .

Understanding the genetic targets of natural selection is one of the most challenging goals of population genetics. Some of the earliest candidate genes were identified from associations between allozyme allele frequencies and environmental variation. One such example is the clinal polymorphism in the arginine kinase () gene in the marine snail . While other enzyme loci do not show differences in allozyme frequencies among populations, the alleles are near differential fixation across repeated wave exposure gradients in Europe. Here, we use this case to illustrate how a new sequencing toolbox can be employed to characterize the genomic architecture associated with historical candidate genes. We found that the alleles differ by nine nonsynonymous substitutions, which perfectly explain the different migration patterns of the allozymes during electrophoresis. Moreover, by exploring the genomic context of the gene, we found that the three main alleles are located on different arrangements of a putative chromosomal inversion that reaches near fixation at the opposing ends of two transects covering a wave exposure gradient. This shows is part of a large (3/4 of the chromosome) genomic block of differentiation, in which is unlikely to be the only target of divergent selection. Nevertheless, the nonsynonymous substitutions among alleles and the complete association of one allele with one inversion arrangement suggest that the gene is a strong candidate to contribute to the adaptive significance of the inversion.