Amino acid substitution at the Adh locus of Drosophila is facilitated by small population size.

The number of amino acid replacement substitutions and that of synonymous substitutions are examined by using DNA sequences of the Adh locus of Drosophila. The ratio of replacement to synonymous substitutions is higher in sequence comparisons between species than in polymorphisms within species. The ratio for the between-species comparisons is highest in the Hawaiian group and lowest in the obscura group. These observations suggest that amino acid substitutions are facilitated by small population size. The result is in accord with the nearly neutral theory of molecular evolution.