Adaptive Introgression of Anticoagulant Rodent Poison Resistance by Hybridization between Old World Mice

Abstract

Summary It is known that evolution by selection on new or standing single nucleotide polymorphisms (SNPs) in the vitamin K 2,3-epoxide reductase subcomponent 1 (vkorc1) of house mice (Mus musculus domesticus) can cause resistance to anticoagulant rodenticides such as warfarin [1–3]. Here we report an introgression in European M. m. domesticus spanning as much as ~20.3 megabases (Mb) and including vkorc1, the molecular target of anticoagulants [1–4], that stems from hybridization with the Algerian mouse (M. spretus). We show that in the laboratory the homozygous complete vkorc1 allele of M. spretus confers resistance when introgressed into M. m. domesticus. Consistent with selection on the introgression after the introduction of rodenticides in the 1950s we document historically adaptive population genetics of vkorc1 in M. m. domesticus. Furthermore, we detected adaptive protein evolution of vkorc1 in the M. spretus lineage (Ka/Ks=1.54–1.93) resulting in radical amino-acid substitutions that apparently have anticoagulant tolerance of M. spretus as pleiotropic effect. Thus, positive selection produced an adaptive, divergent and pleiotropic vkorc1 allele in the donor species, M. spretus, which crossed a species barrier where it is expressed as adaptive trait in the recipient species, M. m. domesticus. Resistant house mice originated from selection on new or standing vkorc1 polymorphisms and from selection on vkorc1 polymorphisms acquired by adaptive introgressive hybridization.