Otsuka J, Kawai Y, Sugaya N
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo, Noda, Japan.
J Theor Biol. 2001 Nov 21;213(2):129-44. doi: 10.1006/jtbi.2001.2407.
In most studies of molecular evolution, the nucleotide base at a site is assumed to change with the apparent rate under functional constraint, and the comparison of base changes between homologous genes is thought to yield the evolutionary distance corresponding to the site-average change rate multiplied by the divergence time. However, this view is not sufficiently successful in estimating the divergence time of species, but mostly results in the construction of tree topology without a time-scale. In the present paper, this problem is investigated theoretically by considering that observed base changes are the results of comparing the survivals through selection of mutated bases. In the case of weak selection, the time course of base changes due to mutation and selection can be obtained analytically, leading to a theoretical equation showing how the selection has influence on the evolutionary distance estimated from the enumeration of base changes. This result provides a new method for estimating the divergence time more accurately from the observed base changes by evaluating both the strength of selection and the mutation rate. The validity of this method is verified by analysing the base changes observed at the third codon positions of amino acid residues with four-fold codon degeneracy in the protein genes of mammalian mitochondria; i.e. the ratios of estimated divergence times are fairly well consistent with a series of fossil records of mammals. Throughout this analysis, it is also suggested that the mutation rates in mitochondrial genomes are almost the same in different lineages of mammals and that the lineage-specific base-change rates indicated previously are due to the selection probably arising from the preference of transfer RNAs to codons.
在大多数分子进化研究中，假定位点上的核苷酸碱基在功能限制下以表观速率发生变化，并且同源基因之间碱基变化的比较被认为会产生与位点平均变化率乘以分歧时间相对应的进化距离。然而，这种观点在估计物种分歧时间方面并不十分成功，大多只是构建了没有时间尺度的树拓扑结构。在本文中，通过考虑观察到的碱基变化是比较经选择存活的突变碱基的结果，从理论上对这个问题进行了研究。在弱选择的情况下，可以解析地得到由于突变和选择导致的碱基变化的时间进程，从而得到一个理论方程，该方程展示了选择如何影响从碱基变化计数估计的进化距离。这一结果提供了一种新方法，通过评估选择强度和突变率，从观察到的碱基变化中更准确地估计分歧时间。通过分析哺乳动物线粒体蛋白质基因中具有四重密码子简并性的氨基酸残基的第三密码子位置观察到的碱基变化，验证了该方法的有效性；也就是说，估计分歧时间的比率与一系列哺乳动物化石记录相当吻合。在整个分析过程中，还表明哺乳动物不同谱系中线粒体基因组的突变率几乎相同，并且先前指出的谱系特异性碱基变化率可能是由于转运RNA对密码子的偏好所产生的选择导致的。
