EVIDENCE FOR ADAPTIVE EVOLUTION OF THE G6PD GENE IN THE DROSOPHILA-MELANOGASTER AND DROSOPHILA-SIMULANS LINEAGES

Proponents of the neutral theory argue that evolution at the molecular level largely reflects a process of random genetic drift of neutral m utations. Under this theory, levels of interspecific divergence and in traspecific polymorphism are expected to be correlated across classes of nucleotide or amino acid sequences with different degrees of functi onal constraint, such as synonymous and replacement sites. Nucleotide sites with reduced polymorphism should show comparably reduced levels of interspecific divergence. To examine this hypothesis, we have seque nced 32 and 12 copies of the glucose-6-phosphate dehydrogenase (G6pd) gene in Drosophila melanogaster and Drosophila simulans, respectively. Both species exhibit similar levels of nucleotide polymorphism at syn onymous sites. D. melanogaster shows two amino acid polymorphisms, one associated with the cosmopolitan allozyme polymorphism and a second w ith an allozyme polymorphism endemic to European and North African pop ulations. In contrast, D. simulans shows no replacement polymorphism. While synonymous divergence between species is 10%, which is typical o f other genes, there are 21 replacement differences. This level of ami no acid sequence divergence, when contrasted with levels of amino acid polymorphism, silent polymorphism, and divergence, is in 10-fold exce ss over that expected under the neutral model of molecular evolution. We propose that this excess divergence reflects episodes of natural se lection on G6pd resulting in fixation of advantageous amino acid mutat ions in these two recently separated lineages.