Benner S A, Cohen M A, Gonnet G H
Institute for Organic Chemistry, Swiss Federal Institute of Technology, Zurich.
J Mol Biol. 1993 Feb 20;229(4):1065-82. doi: 10.1006/jmbi.1993.1105.
The exhaustive matching of the protein sequence database makes possible a broadly based study of insertions and deletions (indels) during divergent evolution. In this study, the probability of a gap in an alignment of a pair of homologous protein sequences was found to increase with the evolutionary distance measured in PAM units (number of accepted point mutations per 100 amino acid residues). A relationship between the average number of amino acid residues between indels and evolutionary distance suggests that a unit 30 to 40 amino acid residues in length remains, on average, undisrupted by indels during divergent evolution. Further, the probability of a gap was found to be inversely proportional to gap length raised to the 1.7 power. This empirical law fits closely over the entire range of gap lengths examined. Gap length distribution is largely independent of evolutionary distance. These results rule out the widely used linear gap penalty as a satisfactory formula for scoring gaps when constructing alignments. Further, the observed gap length distribution can be explained by a simple model of selective pressures governing the acceptance of indels during divergent evolution. Finally, this model provides theoretical support for using indels as part of "parsing algorithms", important in the de novo prediction of the folded structure of proteins from the sequence data.
对蛋白质序列数据库进行详尽匹配，使得在分歧进化过程中对插入和缺失（indels）进行广泛研究成为可能。在本研究中，发现一对同源蛋白质序列比对中出现空位的概率会随着以PAM单位（每100个氨基酸残基中接受的点突变数）衡量的进化距离而增加。indels之间氨基酸残基的平均数量与进化距离之间的关系表明，在分歧进化过程中，平均而言，长度为30至40个氨基酸残基的单元不会被indels打断。此外，发现空位的概率与空位长度的1.7次方成反比。这条经验法则在所研究的整个空位长度范围内都非常吻合。空位长度分布在很大程度上与进化距离无关。这些结果排除了广泛使用的线性空位罚分作为构建比对时空位计分的满意公式。此外，观察到的空位长度分布可以用一个简单的选择压力模型来解释，该模型控制着分歧进化过程中indels的接受情况。最后，该模型为将indels用作“解析算法”的一部分提供了理论支持，这在从序列数据从头预测蛋白质折叠结构中很重要。
