Nonsynonymous substitution

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A nonsynonymous substitution is a nucleotide mutation that alters the amino acid sequence of a protein. It is contrasted with synonymous substitution which do not alter amino acid sequences. As nonsynonymous substitutions result in a biological change in the organism, they are subject to natural selection.

If a gene has lower levels of nonsynonymous than synonymous nucleotide substitution, then it can be inferred to be functional because a Ka/Ks ratio < 1 is a hallmark of sequences that are being constrained to code for proteins.

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