Vkorc1-sequencing of the house mouse (Mus musculus domesticus), Norway rat (Rattus norvegicus), and roof rat (R. rattus) from the USA enables new inferences regarding the evolution and spread of anticoagulant rodenticide resistance

• Main Author: Diaz, Juan C
• Other Authors: Kohn, Michael H
• Format: Thesis
• Language: English
• Published: 2018
• Subjects: Anticoagulant rodenticide; convergent evolution; gene flow; mtDNA; Vkorc1; warfarin resistance; Norway; Rattus rattus
• Online Access: https://hdl.handle.net/1911/108012

Resistance to anticoagulant rodenticides emerged within less than 10 years after their introduction in the 1950s in three species of commensal rodents; the house mouse (Mus musculus domesticus), the Norway rat (Rattus norvegicus), and the roof rat (Rattus rattus). The resistance phenomenon provides an example of evolution in action and how chemical pest control and the movement of animals around the globe can drive it. Resistance is of relevance to public health as resistance impairs rodent control. The study of resistance trait aids understanding of the physiological response of humans to the anticoagulant drug warfarin. Resistance has evolved to first-generation anticoagulants (FGARs), including warfarin, and then, to some second-generation anticoagulant rodenticides (SGARs), including SGARs++, which are recently developed SGARs that are more effective against rodents with resistance to FGARs and SGARs. The resistance phenomenon is a striking example of convergent evolution, as in the three rodent species resistance is at least partly, albeit strongly, mediated by mutations in the vitamin K epoxide reductase subcomponent 1 gene (Vkorc1). Some mutations are shared between the species, such as a Tyr139Cys resistance mutation seen in the house mouse and the Norway rat. In chapter 1 of this thesis, I provide background on rodenticide resistance and the rationale underlying my work. In chapter 2, I compile the published data on the distribution of rodenticide resistance. Available data mainly are in the form of physiological testing for resistance using feeding trials and blood coagulation tests, as well as in form of Vkorc1 nonsynonymous single nucleotide polymorphisms (nsSNPs) used to infer the resistance. Subsets of the nsSNPs are known to be associated with the resistance phenotype, but this association depends on the criteria used, such as to whether nsSNPs cause resistance of practical relevance in the field or merely affect vitamin K cycle kinetics. The survey reveals substantial research efforts were ...