Department of Statistics, University of Wyoming, Laramie, WY 82071, USA.
J Mol Biol. 2010 Mar 12;396(5):1410-21. doi: 10.1016/j.jmb.2009.11.075. Epub 2010 Jan 15.
In Darwinian evolution, mutations occur approximately at random in a gene, turned into amino acid mutations by the genetic code. Some mutations are fixed to become substitutions and some are eliminated from the population. Partitioning pairs of closely related species with complete genome sequences by average population size of each pair, we looked at the substitution matrices generated for these partitions and compared the substitution patterns between species. We estimated a population genetic model that relates the relative fixation probabilities of different types of mutations to the selective pressure and population size. Parameterizations of the average and distribution of selective pressures for different amino acid substitution types in different population size comparisons were generated with a Bayesian framework. We found that partitions in population size as well as in substitution type are required to explain the substitution data. Selection coefficients were found to decrease with increasingly radical amino acid substitution and with increasing effective population size. To further explore the role of underlying processes in amino acid substitution, we analyzed embryophyte (plant) gene families from TAED (The Adaptive Evolution Database), where solved structures for at least one member exist in the Protein Data Bank. Using PAML, we assigned branches to three categories: strong negative selection, moderate negative selection/neutrality, and positive diversifying selection. Focusing on the first and third categories, we identified sites changing along gene family lineages and observed the spatial patterns of substitution. Selective sweeps were expected to create primary sequence clustering under positive diversifying selection. Co-evolution through direct physical interaction was expected to cause tertiary structural clustering. Under both positive and negative selection, the substitution patterns were found to be nonrandom. Under positive diversifying selection, significant independent signals were found for primary and tertiary sequence clustering, suggesting roles for both selective sweeps and direct physical interaction. Under strong negative selection, the signals were not found to be independent. All together, a complex interplay of population genetic and protein thermodynamics forces is suggested.
在达尔文进化论中，突变随机发生在一个基因中，由遗传密码转变成氨基酸突变。有些突变被固定下来成为取代，有些则从种群中消除。通过平均种群大小对具有完整基因组序列的密切相关物种对进行分区，我们观察了为这些分区生成的取代矩阵，并比较了物种之间的取代模式。我们估计了一个种群遗传模型，该模型将不同类型突变的相对固定概率与选择压力和种群大小联系起来。使用贝叶斯框架生成了不同种群大小比较中不同氨基酸取代类型的平均选择压力和分布的参数化。我们发现，需要分区的种群大小以及取代类型才能解释取代数据。选择系数随着越来越激进的氨基酸取代和有效种群大小的增加而降低。为了进一步探索氨基酸取代中潜在过程的作用，我们分析了来自 TAED（适应性进化数据库）的胚胎植物（植物）基因家族，其中至少有一个成员在蛋白质数据库中存在已解决的结构。使用 PAML，我们将分支分配到三个类别：强负选择、中度负选择/中性和阳性多样化选择。我们专注于第一和第三类别，识别沿基因家族谱系变化的位点，并观察取代的空间模式。正多样化选择预计会在积极多样化选择下创建主要序列聚类。通过直接物理相互作用的共同进化预计会导致三级结构聚类。在正选择和负选择下，取代模式被发现是非随机的。在正多样化选择下，主要和三级序列聚类都发现了显著的独立信号，表明选择扫和直接物理相互作用都有作用。在强负选择下，未发现信号独立。总之，建议了种群遗传和蛋白质热力学力之间的复杂相互作用。
