Department of Bioengineering and Bioinformatics, M. V. Lomonosov Moscow State University, Moscow, Russia.
Genome Biol Evol. 2011;3:1006-13. doi: 10.1093/gbe/evr086. Epub 2011 Aug 22.
Detecting positive selection is a challenging task. We propose a method for detecting past positive selection through ongoing negative selection, based on comparison of the parameters of intraspecies polymorphism at functionally important and selectively neutral sites where a nucleotide substitution of the same kind occurred recently. Reduced occurrence of recently replaced ancestral alleles at functionally important sites indicates that negative selection currently acts against these alleles and, therefore, that their replacements were driven by positive selection. Application of this method to the Drosophila melanogaster lineage shows that the fraction of adaptive amino acid replacements remained approximately 0.5 for a long time. In the Homo sapiens lineage, however, this fraction drops from approximately 0.5 before the Ponginae-Homininae divergence to approximately 0 after it. The proposed method is based on essentially the same data as the McDonald-Kreitman test but is free from some of its limitations, which may open new opportunities, especially when many genotypes within a species are known.
检测正选择是一项具有挑战性的任务。我们提出了一种通过持续的负选择来检测过去正选择的方法，该方法基于比较功能重要性和选择中性位点上的种内多态性的参数，这些位点最近发生了相同类型的核苷酸替换。在功能重要的位点上，最近替换的祖先等位基因的出现频率降低表明，负选择目前对这些等位基因起作用，因此，它们的替换是由正选择驱动的。将该方法应用于黑腹果蝇谱系表明，适应性氨基酸替换的分数在很长一段时间内保持在 0.5 左右。然而，在智人谱系中，该分数在猩猩科-人科分歧之前约为 0.5，之后约为 0。所提出的方法基于与 McDonald-Kreitman 检验基本相同的数据，但没有其一些局限性，这可能会开辟新的机会，特别是当一个物种内有许多基因型时。
