Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Barcelona 08193, Spain.
Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Barcelona 08193, Spain.
G3 (Bethesda). 2022 Sep 30;12(10). doi: 10.1093/g3journal/jkac206.
The McDonald and Kreitman test is one of the most powerful and widely used methods to detect and quantify recurrent natural selection in DNA sequence data. One of its main limitations is the underestimation of positive selection due to the presence of slightly deleterious variants segregating at low frequencies. Although several approaches have been developed to overcome this limitation, most of them work on gene pooled analyses. Here, we present the imputed McDonald and Kreitman test (impMKT), a new straightforward approach for the detection of positive selection and other selection components of the distribution of fitness effects at the gene level. We compare imputed McDonald and Kreitman test with other widely used McDonald and Kreitman test approaches considering both simulated and empirical data. By applying imputed McDonald and Kreitman test to humans and Drosophila data at the gene level, we substantially increase the statistical evidence of positive selection with respect to previous approaches (e.g. by 50% and 157% compared with the McDonald and Kreitman test in Drosophila and humans, respectively). Finally, we review the minimum number of genes required to obtain a reliable estimation of the proportion of adaptive substitution (α) in gene pooled analyses by using the imputed McDonald and Kreitman test compared with other McDonald and Kreitman test implementations. Because of its simplicity and increased power to detect recurrent positive selection on genes, we propose the imputed McDonald and Kreitman test as the first straightforward approach for testing specific evolutionary hypotheses at the gene level. The software implementation and population genomics data are available at the web-server imkt.uab.cat.
麦当劳-克里坦门检验是检测和量化 DNA 序列数据中反复出现的自然选择的最强大和最广泛使用的方法之一。它的主要局限性之一是由于频率较低的轻微有害变体的存在而低估了正选择。尽管已经开发了几种方法来克服这一限制，但大多数方法都适用于基因池分析。在这里，我们提出了一种新的直接方法——推断的麦当劳-克里坦门检验（impMKT），用于检测基因水平上的适应度效应分布的正选择和其他选择成分。我们比较了推断的麦当劳-克里坦门检验和其他广泛使用的麦当劳-克里坦门检验方法，同时考虑了模拟数据和实际数据。通过在基因水平上将推断的麦当劳-克里坦门检验应用于人类和果蝇数据，与之前的方法相比，我们大大增加了正选择的统计证据（例如，与果蝇和人类中的麦当劳-克里坦门检验相比，分别增加了 50%和 157%）。最后，我们通过使用推断的麦当劳-克里坦门检验与其他麦当劳-克里坦门检验的实现，回顾了在基因池分析中获得适应替代比例（α）可靠估计所需的最小基因数量。由于其简单性和增加的检测基因上反复发生的正选择的能力，我们建议推断的麦当劳-克里坦门检验作为在基因水平上测试特定进化假设的第一个直接方法。软件实现和群体基因组学数据可在 web 服务器 imkt.uab.cat 上获得。
