DNAの進化と変異の機構

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Molecular mechanism of gene evolution has been a fundamental problem in evolutionary biology for many years. One focus of controversy concerns the effect and significance of natural selection. The present study mainly put a focus on dissection of DNA changes into nonsynonymous and synonymous substitutions which occurred among closely related species in mammals and Drosophila. Amino-acid-altering substitution, or nonsynonymous substitution, is naturally considered to be more exposed to natural selection than synonymous change. Thus, the comparison between these two patterens in a gene provides a good opportunity to evaluate the effect of natural selection. Along this line, we studied the pattern of molecular evolution in mammalian and Drosophila genes. Particularly, we could reveal that the ratio of replacement to synonymous changes in the lineage leading to rodent is lower than that in the primate lineage. This is consistent with the nearly neutral mutation model, which advocates that most of amino acid changes are slightly deleterious. The variation in nonsynonymous substitution among lineages was significant in mammals after weighting the lineage effects. The ratio of replacement to synonymous substitutions also varied significantly among lineages for some of the genes studied in Drosophila. This episodic molecular evolution cannot be explained by the epistatic effect among amino acid sites. Thus, fluctuation of population size or selective constraint should be taken into consideration. Otherwise, positive Darwinian evolution may have some impact on molecular evolution. Further study on higher-order interaction will be also needed to understand the molecular evolution of the complicated genetic systems and to dissect the effects of natural selection and random genetic drift.