Nearsynonymous

Near-synonymous is an informal term used in genetics and molecular evolution to describe a missense mutation that changes the amino acid encoded by a codon but results in a substitution that is chemically similar to the original amino acid. It is not a formal category in standard nomenclature; the main categories are synonymous (no amino acid change) and nonsynonymous (amino acid change). The idea behind near-synonymous substitutions is that some amino acid changes preserve properties such as size, charge, or hydrophobicity, and therefore may have only a modest effect on protein function.

In practice, near-synonymous substitutions are often described as conservative substitutions. Common examples include changes like leucine to isoleucine or valine to leucine, where the new amino acid has similar physico-chemical characteristics and may be tolerated by the protein without large functional disruption. The concept is closely related to but distinct from strict conservative substitutions used in protein chemistry, and from formal measures of evolutionary constraint.

Significance. In evolutionary analysis, substitutions with near-synonymous effects can contribute genetic variation that is less likely to be strongly deleterious, and therefore more likely to persist in populations. However, the actual impact depends on the protein context, the domain, and the specific structural or functional role of the residue. Consequently, near-synonymous is not a precise predictor of functional impact and should be interpreted with consideration of protein structure and empirical data.

See also: synonymous mutation, nonsynonymous mutation, conservative substitution, dN/dS ratio.