McDonald J H
Department of Biology, University of Delaware, Newark 19716, USA.
Mol Biol Evol. 1996 Jan;13(1):253-60. doi: 10.1093/oxfordjournals.molbev.a025562.
Natural selection, in the form of balancing selection or selective sweeps, can result in a decoupling of the amounts of molecular polymorphism and divergence. Thus natural selection can cause some areas of DNA sequence to have greater silent polymorphism, relative to divergence between species, than other areas. It would be useful to have a statistical test for heterogeneity in the polymorphism to divergence ratio across a region of DNA sequence, one that could identify heterogeneity greater than that expected from the neutral processes of mutation, drift, and recombination. The only currently available test requires that a region be arbitrarily divided into sections that are compared with each other, and the subjectivity of this division could be problematic. Here a test is proposed in which runs of polymorphic and fixed sites are counted, where a "run" is a set of one or more sites of one type preceded and followed by the other type. The number of runs is smaller than otherwise expected if polymorphisms are clumped together. By simulating neutral evolution and comparing the observed number of runs to the simulations, a statistical test is possible which does not require any a priori decisions about subdivision.
以平衡选择或选择性清除形式存在的自然选择，可能导致分子多态性和分化程度的解耦。因此，自然选择会使某些DNA序列区域相对于物种间的分化，具有比其他区域更高的沉默多态性。对于DNA序列区域内多态性与分化率的异质性，进行统计检验将很有用，这种检验能够识别出大于由突变、漂变和重组等中性过程所预期的异质性。目前唯一可用的检验方法要求将一个区域任意划分为多个部分并相互比较，而这种划分的主观性可能会带来问题。本文提出一种检验方法，即统计多态性位点和固定位点的连续段，其中“连续段”是指一种类型的一个或多个位点的集合，其前后为另一种类型的位点。如果多态性位点聚集在一起，那么连续段的数量会比预期的少。通过模拟中性进化并将观察到的连续段数量与模拟结果进行比较，就可以进行一种无需对划分做任何先验决策的统计检验。
