Polymorphism Of Anticoagulant Resistance Target Genes In Rodent And Its Application In The Assessment Of Resistance In Rattus Tanezumi

Rodents are one of the most widely distributed mammals in the world.Some pest rodents destroyed crops,damaged animal husbandry,and carried a variety of zoonotic diseases.Anticoagulant rodenticides have been widely used for the rodent control around the world,but anticoagulant resistance has greatly impaired the efficacy of the rodenticides.While the generation of anticoagulant resistance in most rodent populations was owing to the selection by anticoagulant rodenticides,some rodents living in arid areas showed natural anticoagulant resistance.Vitamin K epoxide reductase complex subunit 1(Vkorc1)gene is the target of anticoagulant rodengticides and plays a key role in the Vitamin K cycle.Mutations in Vkorc1 gene can cause anticoagulant resistance in different rodent species.In addition,the NAD(P)H Quinone Dehydrogenase 1(Nqo1)and Gamma-Glutamyl Carboxylase(Ggcx)have also been suggested to be related to anticoagulant resistance in rodents or human.In this study,we first analyzed the polymorphisms in the genes Vkorc1,Nqo1 and Ggcx and detected the adaptive evolution signal on these genes in desert or semi-desert rodents,as compared to rodents living in normal circumstance.Then we analyzed the Vkorc1 polymorphisms in Rattus tanezumi to evaluate resistance level of different populations.The results were shown below:1.Rodents living in arid condition showed a faster evolutionary rate in the Vkorc1 and strong selection signal was detected in the Vkorc1 of Mus spretus and Psammomys obesus.However,no selection signal was detected in the Ggcx and Nqo1 gene in any rodent species.The accelerated evolution of Vkorc1 in M.spretus and P.obesus,could be owing to adaptation to vitamin K-deficient diet in arid circumstance.2.We found 3 mutations Ala26 Thr,Ala41Ala and Tyr139 Cys in R.tanezumi population.It's already known that Tyr139 Cys can cause resistance to the first and second generation of anticoagulant rodenticides in different rodents.In this study,we found the resistance mutation Tyr139 Cys in R.tanezumi from the provinces of Sichuan,Guangdong,Fujian,Hunan and Tibet.The resistance frequency in Hunan populations reached 66.7%.We further estimated the resistance population structure based on the mitochondrial D-loop region and found that the Tyr139 Cys in Tibet might spread from Sichuan.Our findings suggested the frequency of Tyr139 Cys mutation could be used for monitoring the resistance level of the R.tanzumi population in China.The Ala26 Thr could be associated with anticoagulant resistance,but need further verification.In this study,we analyzed the Vkorc1 polymorphisms in different rodent species and revealed strong selection signal in the Vkorc1 of some rodents living in arid circumstance.We further analyzed the Vkorc1 polymorphisms in R.tanzumi population and evaluated the resistance frequency of different populations,which provided theoretical guidance for the scientific use of anticoagulant rodenticides.