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.

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

“…The combination of R12W, A26S, and A48T in exon 1 associated with the R61L mutation in exon 2 was previously described as the Vkorc1 spr genotype (Song et al., 2011). However, other mutations were found to be present on the same allele of Vkorc1 .…”

Adaptive introgression in an African malaria mosquito coincident with the increased usage of insecticide-treated bed nets

“…For adaptive introgression to occur, a beneficial mutation should cross the species barrier through a rare hybridization event and overcome any fitness cost incurred from hybrid incompatibilities. The most well-characterized animal examples include warfarin resistance in European house mice (36) and melanism in North American gray wolves (37). Adaptive introgression of an insecticide-resistance gene between A. gambiae and A. coluzzii has been reported in numerous papers (12,19,(38)(39)(40)(41).…”

Introgression and gene family contraction drive the evolution of lifestyle and host shifts of hypocrealean fungi

“…Recent studies have revealed several mechanisms, including introgression, that can lead to adaptive divergence, especially in rapidly radiating groups (Pease et al 2016). There are numerous striking examples of adaptive introgression in plants, animals and humans that illustrate functional introgressed loci contributing to ecologically and reproductively significant traits (Whitney et al 2006; Song et al 2011; Sankararaman et al 2014; Lamichhaney et al 2015). Epichloë spp., grass endophytes in Hypocreales, contain many species that have evolve through a complex process of hybridisation (Moon et al 2004), indicating there is high possibility for the occurrence of introgression.…”