Sawyer Stanley A, Kulathinal Rob J, Bustamante Carlos D, Hartl Daniel L
Department of Mathematics, Washington University, St. Louis, MO 63130, USA.
J Mol Evol. 2003;57 Suppl 1:S154-64. doi: 10.1007/s00239-003-0022-3.
One of the principal goals of population genetics is to understand the processes by which genetic variation within species (polymorphism) becomes converted into genetic differences between species (divergence). In this transformation, selective neutrality, near neutrality, and positive selection may each play a role, differing from one gene to the next. Synonymous nucleotide sites are often used as a uniform standard of comparison across genes on the grounds that synonymous sites are subject to relatively weak selective constraints and so may, to a first approximation, be regarded as neutral. Synonymous sites are also interdigitated with nonsynonymous sites and so are affected equally by genomic context and demographic factors. Hence a comparison of levels of polymorphism and divergence between synonymous sites and amino acid replacement sites in a gene is potentially informative about the magnitude of selective forces associated with amino acid replacements. We have analyzed 56 genes in which polymorphism data from D. simulans are compared with divergence from a reference strain of D. melanogaster. The framework of the analysis is Bayesian and assumes that the distribution of selective effects (Malthusian fitnesses) is Gaussian with a mean that differs for each gene. In such a model, the average scaled selection intensity (gamma = N(e)s) of amino acid replacements eligible to become polymorphic or fixed is -7.31, and the standard deviation of selective effects within each locus is 6.79 (assuming homoscedasticity across loci). For newly arising mutations of this type that occur in autosomal or X-linked genes, the average proportion of beneficial mutations is 19.7%. Among the amino acid polymorphisms in the sample, the expected average proportion of beneficial mutations is 47.7%, and among amino acid replacements that become fixed the average proportion of beneficial mutations is 94.3%. The average scaled selection intensity of fixed mutations is +5.1. The presence of positive selection is pervasive with the single exception of kl-5, a Y-linked fertility gene. We find no evidence that a significant fraction of fixed amino acid replacements is neutral or nearly neutral or that positive selection drives amino acid replacements at only a subset of the loci. These results are model dependent and we discuss possible modifications of the model that might allow more neutral and nearly neutral amino acid replacements to be fixed.
群体遗传学的主要目标之一是了解物种内的遗传变异(多态性)转化为物种间遗传差异(分歧)的过程。在这种转变中,选择中性、近中性和正选择可能各自发挥作用,因基因而异。同义核苷酸位点常被用作跨基因比较的统一标准,因为同义位点受到相对较弱的选择限制,所以初步近似可视为中性。同义位点也与非同义位点相互交错,因此同样受到基因组背景和人口统计学因素的影响。因此,比较一个基因中同义位点和氨基酸替换位点的多态性水平和分歧程度,可能有助于了解与氨基酸替换相关的选择力大小。我们分析了56个基因,将拟暗果蝇的多态性数据与黑腹果蝇参考菌株的分歧数据进行了比较。分析框架是贝叶斯的,并假设选择效应(马尔萨斯适合度)的分布是高斯分布,每个基因的均值不同。在这样一个模型中,有资格成为多态性或固定的氨基酸替换的平均标度选择强度(γ = N(e)s)为-7.31,每个位点内选择效应的标准差为6.79(假设位点间方差齐性)。对于常染色体或X连锁基因中发生的此类新出现突变,有益突变的平均比例为19.7%。在样本中的氨基酸多态性中,有益突变的预期平均比例为47.7%,在固定的氨基酸替换中,有益突变的平均比例为94.3%。固定突变的平均标度选择强度为+5.1。除了Y连锁的生育基因kl-5外,正选择普遍存在。我们没有发现证据表明很大一部分固定的氨基酸替换是中性或近中性的,也没有发现正选择仅在一部分位点驱动氨基酸替换的证据。这些结果依赖于模型,我们讨论了可能对模型进行的修改,这些修改可能会使更多中性和近中性的氨基酸替换得以固定。