Nearly neutral theory is an extension of the neutral theory and contends that the borderline mutations, whose effects lie between the selected and the neutral classes, are important at the molecular level. Under the strict neutral theory, the evolutionary rate is equal to the neutral mutation rate. Under the near-neutrality, the situation is not so simple and the most significant difference between the neutral and the nearly neutral theories is that the latter predicts a negative correlation between evolutionary rate and species population size. The nearly neutral theory also predicts abundant rare alleles in the population as compared with strict neutrality. Genome-wide data on protein evolution are mostly in accord with the nearly neutral theory. Genetic regulatory systems are highly complex. The near-neutrality concept may be extended to the evolution of such systems, where epigenetics and robustness are important for gene expression and many mutations are weakly selected.

Key Concepts:

• The emphasis of significance of weak selection in evolution distinguishes the nearly neutral theory from the neutral theory.
  
• The nearly neutral theory contends that the interplay of drift and weak selection is important and predicts that evolution is more rapid in small populations than in large populations.
  
• Many observed patterns of protein evolution by measuring synonymous and nonsynonymous divergences are in accord with the nearly neutral theory.
  
• Observed molecular polymorphisms within a population often show abundance of rare alleles, in accord with the prediction of the nearly neutral theory.
  
• Numerous complex systems work together in living cells such as those in chromatin modelling/remodelling and in various signalling pathways. Interplay of drift and weak selection is important for evolution of such complex systems.