Nonsynonymous

In genetics, a nonsynonymous mutation is a nucleotide substitution in a coding region of DNA that changes the amino acid sequence of the encoded protein. These differ from synonymous mutations, which due to the redundancy of the genetic code do not alter the amino acid sequence. Nonsynonymous mutations include missense mutations, which substitute one amino acid for another, and nonsense mutations, which create a premature stop codon and truncate the protein.

The phenotypic impact of nonsynonymous mutations depends on where in the protein the change occurs and on the properties of the substituted amino acids. Many nonsynonymous changes are deleterious and removed by purifying selection; others are neutral and persist, and some are beneficial and may drive adaptation.

In evolutionary biology, the rate of nonsynonymous substitutions (dN) relative to the rate of synonymous substitutions (dS) is used to infer selection on a gene. A dN/dS ratio greater than 1 suggests positive selection, less than 1 indicates purifying selection, and around 1 implies neutral evolution.

In practice, predicting the effect of a nonsynonymous mutation requires consideration of protein structure, functional domains, and interaction networks; experimental assays or computational tools (for example, structural modeling or conservation analysis) are used to assess potential impacts.