Warfarin resistance: a balanced polymorphism in the Norway rat

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Abstract
SUMMARY: The frequency of monogenic resistance to anticoagulant rodenticides in Rattus norvegicus in an area straddling the England–Wales border was monitored from 1967 until 1975. Rats were trapped on farms and tested in the laboratory by administering a dose of warfarin lethal to susceptibles. The mean incidence of resistance was 44% and did not change significantly, despite the extensive use of anticoagulants by farmers during the 9-year period. In 1975 more refined techniques showed that the frequencies of susceptible (SS) and resistant (RR) homozygotes were significantly below the Hardy–Weinberg expectations and simple estimates of the relative fitness ratios for the RR, RS and SS phenotypes were 0·37, 1·0 and 0·68 respectively. In two relatively isolated valleys, where selection with anticoagulants was minimal, the frequency of resistance decreased significantly from 57% to 39% during 1973–5. The results are consistent with the hypothesis that a balanced polymorphism is being maintained. Selection against susceptible homozygotes by the use of anticoagulant rodenticides, and against the resistant homozygote due to its high susceptibility to a primary deficiency of vitamin K gives the heterozygotes a selective advantage. A number of ecological factors that influence the incidence of the resistance are discussed briefly.
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