McVean Gil, Awadalla Philip, Fearnhead Paul
Department of Statistics, University of Oxford, Oxford OX1 3TG, United Kingdom.
Genetics. 2002 Mar;160(3):1231-41. doi: 10.1093/genetics/160.3.1231.
Determining the amount of recombination in the genealogical history of a sample of genes is important to both evolutionary biology and medical population genetics. However, recurrent mutation can produce patterns of genetic diversity similar to those generated by recombination and can bias estimates of the population recombination rate. Hudson 2001 has suggested an approximate-likelihood method based on coalescent theory to estimate the population recombination rate, 4N(e)r, under an infinite-sites model of sequence evolution. Here we extend the method to the estimation of the recombination rate in genomes, such as those of many viruses and bacteria, where the rate of recurrent mutation is high. In addition, we develop a powerful permutation-based method for detecting recombination that is both more powerful than other permutation-based methods and robust to misspecification of the model of sequence evolution. We apply the method to sequence data from viruses, bacteria, and human mitochondrial DNA. The extremely high level of recombination detected in both HIV1 and HIV2 sequences demonstrates that recombination cannot be ignored in the analysis of viral population genetic data.
确定基因样本系谱历史中的重组量,对进化生物学和医学群体遗传学都很重要。然而,反复突变会产生与重组所产生的模式相似的遗传多样性模式,并可能使群体重组率的估计产生偏差。哈德森在2001年提出了一种基于合并理论的近似似然方法,用于在无限位点序列进化模型下估计群体重组率4N(e)r。在此,我们将该方法扩展到基因组重组率的估计,比如许多病毒和细菌的基因组,这些基因组中反复突变的发生率很高。此外,我们开发了一种强大的基于置换的重组检测方法,该方法比其他基于置换的方法更强大,并且对序列进化模型的错误设定具有鲁棒性。我们将该方法应用于病毒、细菌和人类线粒体DNA的序列数据。在HIV1和HIV2序列中检测到的极高重组水平表明,在分析病毒群体遗传数据时,重组不能被忽视。