Partridge G G
Heredity (Edinb). 1979 Oct;43(2):239-46. doi: 10.1038/hdy.1979.79.
Resistance to warfarin and an increased vitamin K requirement appear to be pleiotropic effects of the same allele (Rw2). In a natural population containing resistant individuals where the use of warfarin is discouraged the change in the frequency of resistance should reflect the relative fitnesses of the three possible genotypes. A large polymorphic population of rats was extensively poisoned with warfarin and the level of resistance monitored regularly for a period of 18 months after withdrawal of the poison. During this period the proportion of resistant animals in live-capture samples decreased significantly from approximately 80 per cent to 33 per cent. This decline is consistent with a hypothesis of reduced fitness of both Rw2Rw2 and Rw1Rw2 genotypes relative to Rw1Rw1 under natural conditions. The relative fitnesses of these genotypes were calculated using an optimisation method based on least squares analysis. These estimates were: Rw2Rw2 (0.46), Rw1Rw2 (0.77) and Rw1Rw1 (1.00). Homozygous resistant individuals were found in some of the samples, confirming that the Rw2 allele does not act as a recessive lethal, although it must be extremely disadvantageous. Some heterogeneity was observed in the proportion of resistant animals in samples taken from different areas of the farm building complex. This could reflect stochastic processes influencing the Rw2 allele frequency in small peripheral populations.
对华法林的抗性以及维生素K需求的增加似乎是同一等位基因（Rw2）的多效性效应。在一个含有抗性个体的自然种群中，由于不鼓励使用华法林，抗性频率的变化应反映三种可能基因型的相对适合度。用华法林对一大群多态性大鼠进行广泛毒杀，并在停止投毒后的18个月内定期监测抗性水平。在此期间，活捕样本中抗性动物的比例从约80%显著下降至33%。这种下降与在自然条件下Rw2Rw2和Rw1Rw2基因型相对于Rw1Rw1适合度降低的假设一致。这些基因型的相对适合度是使用基于最小二乘法分析的优化方法计算得出的。这些估计值为：Rw2Rw2（0.46）、Rw1Rw2（0.77）和Rw1Rw1（1.00）。在一些样本中发现了纯合抗性个体，这证实了Rw2等位基因并非隐性致死基因，尽管它必定极为不利。在从农场建筑群不同区域采集的样本中，抗性动物的比例存在一些异质性。这可能反映了影响小边缘种群中Rw2等位基因频率的随机过程。
