The Nearly Neutral Theory of Molecular Evolution

摘要

The neutral theory of molecular evolution was put forward by M. Kimura. The neutral theory proposes that the evolution of genes is by random genetic drift and not by selec-tion. In this theory, new mutations are classified into deleterious, neutral and advanta-geous classes. I realized that the intermediate class of mutations between the selected and neutral classes must be important and, in 1973, proposed the nearly neutral theory of molecular evolution. The nearly neutral theory emphasizes the interaction of drift and selection. With the rapidly increasing availability of genome data, the applicability of the nearly neutral theory is expanding. In this report, I review recent progress on the ap-plicability of the nearly neutral theory in relation to the evolution of complex systems, at the following two levels:(1) Protein coding regions: The most important prediction of the nearly neutral theory is the rapid evolution of species with a small population size compared with those with a large population size. This prediction has been verified by comparative studies of synonymous and nonsynonymous substitutions among various species. Further, DNA polymorphism data for various species show a preponderance of slightly deleterious mutations.(2) Gene regulations: It is now recognized that genetic regulatory systems are robust against muta-tions. Because of such robust systems, individual mutant substitutions may become nearly neutral. After several mutant substitutions, however, a path may be opened for the creation of novel systems. The extra transcription activity of the human genome also depends upon the robustness, and flexibil-ity of the system is provided by nearly neutral variations.At these two levels, complex systems are thought to differ in how they respond to selection pressure. In particular, when compared with protein evolution, the evolution of gene regulation is character-ized by very rapid changes. This phenomenon is thought to arise from the flexibility of gene regula-tory systems allowing then to readily respond to environmental changes. Drift and selection work together on shifting complex systems, providing opportunity for evolution of novel forms and func-tions. In the shifting process, robustness and epigenetics provide various opportunities for the evolu-tion of novel systems. We can visualize these complicated processes as large grey zones comprising weak selection, drift, robust genetic networks and epigenetics.