Nunney Leonard, Schuenzel Erin L
Department of Biology, University of California, Riverside, CA 92521, USA.
J Mol Evol. 2006 Feb;62(2):176-95. doi: 10.1007/s00239-004-0334-y. Epub 2006 Jan 13.
An important criterion used to detect adaptive evolution in DNA sequence data is omega(i) > 1, where omega(i) is the ratio of nonsynonymous to synonymous substitution rates in lineage i. However, the evaluation of multiple omega(i) within a phylogenetic tree can easily inflate the statistical type I error rate. We developed two rigorous methods of analysis that avoid this and other potential pitfalls. We applied these methods to four published examples of adaptive evolution. One case was strongly supported by our reanalysis (abalone sperm lysin), and one was weakly supported (baboon alpha-globin), but two examples (primate lysozyme and Antarctic fish beta-globin) did not show significant evidence of adaptive evolution. Our first method is a "bottom-up" hierarchical maximum likelihood approach, which (1) tests for significant heterogeneity in omega across the phylogeny, (2) locates its source using a sequence of planned comparisons, and (3) tests homogeneous groups of omega for omega > 1, using a modified level of significance that incorporates the pretesting. The second method is a "top-down" log-linear analysis based on estimates of nonsynonymous and synonymous substitutions in pairs of lineages. The log-linear test is applied to pairs of lineages joined at progressively deeper nodes. For each pair, the analysis simultaneously tests for adaptive evolution (omega > 1), a shift in natural selection (omega1 does not = omega2), and unequal evolution rate (the relative rate test). In both tests, we emphasized that the criterion omega1 not equal omega2 is an important additional indicator of a phylogenetic shift in the balance between natural selection and genetic drift between two related lineages.
用于检测DNA序列数据中适应性进化的一个重要标准是ω(i)>1，其中ω(i)是谱系i中非同义替换率与同义替换率的比值。然而，在系统发育树中对多个ω(i)进行评估很容易夸大统计I型错误率。我们开发了两种严格的分析方法来避免这种情况和其他潜在的陷阱。我们将这些方法应用于四个已发表的适应性进化实例。我们的重新分析强烈支持了一个案例（鲍鱼精子溶菌酶），微弱支持了一个案例（狒狒α-珠蛋白），但有两个实例（灵长类溶菌酶和南极鱼β-珠蛋白）没有显示出适应性进化的显著证据。我们的第一种方法是“自下而上”的分层最大似然法，该方法(1)测试整个系统发育中ω的显著异质性，(2)使用一系列计划比较来确定其来源，(3)使用纳入预测试的修正显著性水平，测试ω的同质子组是否ω>1。第二种方法是基于谱系对中非同义替换和同义替换估计的“自上而下”对数线性分析。对数线性检验应用于在逐渐更深的节点处连接的谱系对。对于每一对，分析同时测试适应性进化(ω>1)、自然选择的转变(ω1≠ω2)和不等进化速率（相对速率检验）。在这两种检验中，我们强调标准ω1≠ω2是两个相关谱系之间自然选择和遗传漂变平衡的系统发育转变的一个重要附加指标。
