Abstract
The nearly neutral theory emphasizes the interaction of drift and weak selection in evolution. With progress of genome biology, the applicability of the nearly neutral theory has expanded. The genome-wide analyses of synonymous and nonsynonymous substitutions at protein-coding regions show prevalence of very weak selection. Many patterns of evolution of gene regulation are also in agreement with the nearly neutral prediction. Our consideration on near-neutrality expands in relation to the progress on molecular understanding of robustness and epigenetics. Both are bridges to link genotypes with phenotypes and important for understanding how weak selection and drift interact in the evolution of complex systems.