Summary
Dominant warfarin resistance and a recessive haemorrhagic trait are apparently controlled by the same allele Rw2.
Twenty-eight F2 litters and 18 backcross litters of wild rats were scored for resistance when 8 weeks of age. There was a deficiency of resistant males in the F2 litters whereas phenotypic ratios were close to expectation in F2 females and backcrosses. Any deficiency of resistant males in F2 litters could be due to the selective death of the Rw2Rw2 genotype. The size of F2 and backcross litters at birth is similar whereas by 8 weeks the former are significantly smaller than the latter.
Samples of rats from populations in mid Wales were scored for resistance. There was a significant decline in the frequency of phenotypic resistance in one large population (N≈500) starting when the frequency of the Rw2 allele was relatively low (c. 0·10–0·23). Since few alleles can be lost by selective death of Rw2Rw2 males in these circumstances it appears that, in the absence of warfarin, the heterozygote may also be at a selective disadvantage.
Where rats are intensively poisoned with warfarin both Rw2 and its alternative Rw1 are maintained in populations by heterozygous advantage. The ecological unreality of the concept of segregational load is discussed.
Strong selection influences the frequency of the alleles of Rw. Chance must also have an important role. Populations of rats in rural areas are widely scattered and sometimes small in size. There is an unpredictable amount of movement between these populations which occur in very heterogeneous environments.
Similar content being viewed by others
Article PDF
References
Bell, R G, and Caldwell, P T. 1973. Mechanism of warfarin resistance. Warfarin and the metabolism of vitamin K1. Biochemistry, 12, 1759–1762.
Bishop, J A, and Hartley, D J. 1976. The size and age structure of rural populations of Rattus norvégiens containing individuals resitant to the anticoagulant poison warfarin. J Anim Ecol, 45, 623–646.
Cain, A J, and Gurrey, J D. 1963. Area effects in Cepaea. Phil Trans R Soc Lond B, 246, 1–81.
Drummond, D C, and Wilson, E J. 1968. Laboratory investigations of resistance to warfarin of Rattus norvégiens in Montgomeryshire and Shropshire. Ann Applied Biol, 61, 303–349.
Dunning, W F, and Curtis, M R. 1939. Linkage in rats between factors determining a pathological condition and a coat colour. Genetics, 24, 70.
Fraser, G R, and Mayo, O. 1974. Genetical load in man. Humangenetik, 23, 83–110.
Greaves, J H, and Ayres, P. 1967. Heritable resistance to warfarin in rats. Nature, Lond, 215, 877–878.
Greaves, J H, and Ayres, P. 1969. Linkages between genes for coat colour and resistance to warfarin in Rattus norvégiens. Nature, Lond, 224, 284–285.
Hartley, D J, and Bishop, J A. 1978. Home range and patterns of movement in rural populations of the brown rat Rattus norvegiens (Berkenhout). J Linn Soc. (in press).
Hermodson, M A, Suttie, J W, and Link, K P. 1969. Warfarin metabolism and vitamin K requirement in the warfarin-resistant rat. Am J Physiol, 217, 1316–1319.
Martin, A D, Steed, L G, Redfern, R, and Gill, E. 1977. Genotype determination in warfarin resistant rats. Lab anim. (in press).
Mellette, S J, and Leone, L A. 1960. Influence of age, sex, strain of rat and fat soluble vitamins on haemorrhagic syndromes in rats fed irradiated beef. Fedn Proc, 19, 1045–1049.
Wallage, M E, and MacSwinney, F J. 1976. A major gene controlling warfarin-resistance in the house mouse. J Hyg, Camb, 76, 173–181.
Wright, S. 1931. Evolution in Mendelian populations. Genetics, 16, 97–159.
Zimmerman, A, and Matschiner, J T. 1974. Biochemical basis of hereditary resistance to warfarin in the rat. Biochem Pharmacol, 23, 1033–1040.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bishop, J., Hartley, D. & Partridge, G. The population dynamics of genetically determined resistance to warfarin in Rattus norvegicus from mid Wales. Heredity 39, 389–398 (1977). https://doi.org/10.1038/hdy.1977.81
Received:
Issue Date:
DOI: https://doi.org/10.1038/hdy.1977.81
This article is cited by
-
Population genetics and genotyping as tools for planning rat management programmes
Journal of Pest Science (2019)
-
Novel mutations in the VKORC1 gene of wild rats and mice – a response to 50 years of selection pressure by warfarin?
BMC Genetics (2009)
-
Local genetic structure within two rookeries of Chelonia mydas (the green turtle)
Heredity (1996)
-
Relationships between genetic polymorphism and herbicide resistance within Alopecurus myosuroides Huds.
Heredity (1994)
-
The number of genes on the second chromosome of Drosophila melanogaster and a comment on the genetic structure of eukaryotes
Heredity (1981)