Adaptative evolution of theVkorc1gene inMus musculus domesticusis influenced by the selective pressure of anticoagulant rodenticides

Anticoagulant rodenticides are commonly used to control rodent pests worldwide. They specifically inhibit the vitamin K epoxide reductase (VKORC1), which is an enzyme encoded by theVkorc1gene, involved in the recycling of vitamin K. Therefore, they prevent blood clotting. Numerous mutations ofVkorc1gene were reported in rodents, and some are involved in the resistant to rodenticides phenotype. Two hundred and sixty‐six mice tails were received from 65 different locations in France. Coding sequences ofVkorc1gene were sequenced in order to detect mutations. Consequences of the observed mutations were evaluated by the use of recombinantVKORC1. More than 70% of mice presentedVkorc1mutations. Among these mice, 80% were homozygous. Contrary to brown rats for which only one predominantVkorc1genotype was found in France, nine missense single mutations and four double mutations were observed in house mice. The single mutations lead to resistance to first‐generation antivitamin K (AVKs) only and are certainly associated with the use of these first‐generation molecules by nonprofessionals for the control of mice populations. The double mutations, probably obtained by genetic recombination, lead to in vitro resistance to allAVKs. They must be regarded as an adaptive evolution to the current use of second‐generationAVKs. The intensive use of first‐generation anticoagulants probably allowed the selection of a high diversity of mutations, which makes possible the genetic recombination and consequently provokes the emergence of the more resistant mutatedVkorc1described to date.