Different parts of genes evolve at different rates. The highest rates of nucleotide substitution are in sequences that have the least effect on protein function.

The lowest rates of substitution are seen in nonsyn-onymous changes in the coding region, because these substitutions always alter the amino acid sequence of the protein and are often deleterious. The highest rates of substitution are in pseudogenes, which are duplicated nonfunctional copies of genes that have acquired mutations. Such a gene no longer produces a functional product; so mutations in pseudogenes have no effect on the fitness of the organism.

In summary, there is a relation between the function of a sequence and its rate of evolution; higher rates are found where they have the least effect on function. This observation fits with the neutral-mutation hypothesis, which predicts that molecular variation is not affected by natural selection.

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