【Animal Modeling】-Why do rodents in arid areas have high drug resistance?

  Recently, the innovation team of grassland pest and rodent monitoring and prevention and control of the Institute of Plant Protection, Chinese Academy of Agricultural Sciences, by comparing the molecular evolution characteristics of drug resistance-related genes of different rat species, revealed that the rapid evolution of the drug resistance target gene Vkorc1 gene is the main reason for the rapid evolution of the drug resistance target gene Vkorc1. It is an important factor in the natural high resistance to anticoagulant rodenticides.

  Anticoagulant rodenticides are the most commonly used chemical rodenticides in rodent control, but rodents are prone to develop resistance to them. Previous studies have found that some rodent species in arid areas are naturally highly resistant to anticoagulant rodenticides, and resistance genes can also be transmitted to sensitive rodent populations through interspecies hybridization, thereby affecting the application of anticoagulant rodenticides.

  Studies have shown that the Vkorc1 gene (vitamin K epoxide reductase subunit 1 gene), the γ-glutamine carboxylase gene and the quinone oxidoreductase 1 gene are associated with drug resistance in mice.

  The team compared and analyzed the molecular evolution characteristics of these three genes among 46 rodent species, and found that the Vkorc1 gene of the arid area rat fat gerbil, the Israeli blind mole and the known highly resistant mouse species, the Mediterranean Mus musculus Rapid evolution took place.

  Further analysis of the 3D model of the protein revealed that the protein was in a "pocket shape". Amino acid mutations in the inner and apical regions of the protein pocket in arid-zone mice may affect the binding of drugs to the protein, resulting in the formation of high drug resistance.

  This study analyzed the molecular mechanism of high drug resistance of rodents in arid areas from an evolutionary perspective, and provided a theoretical reference for rodent control in desert and semi-desert areas.

  The research was funded by the special projects for the investigation of basic scientific and technological resources, the National Natural Science Foundation of China, and the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences.