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why is the ratio of non-synonymous to synonymous nucleotide substitutions used as a measure of selection for a given locus?

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This ratio of non-synonymous to synonymous nucleotide substitutions is used to estimate how quickly gene sequences are evolving.

Since a Ka/Ks ratio of 1 is a defining characteristic of sequences that code for proteins, a gene can be assumed to be functional. A synonymous nucleotide substitution has a lower degree of nonsynonymous substitution. Comparing the rates of fixation of those two types of mutations provides a great tool for understanding the mechanisms since synonymous (silent) mutations are essentially invisible to natural selection while nonsynonymous (amino-acid-replacing) mutations may be under severe selective pressure. Protein sequences are altered by nonsynonymous mutations, which are commonly exposed to natural selection. The same is true for nonsense mutations that cause CDSs to contain premature stop codons (coding sequences).

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