Evidence that Environmental Heterogeneity Maintains a Detoxifying Enzyme Polymorphism in Drosophila melanogaster

Environmental heterogeneity is thought to be an important process maintaining genetic variation in populations [1–4]: if alternative alleles are favored in different environments, a stable polymorphism can be maintained [1, 5, 6]. This situation has been hypothesized to occur in genes encoding multi-substrate enzymes [7], in which changes that increase activity with one substrate typically decrease activity with others [8–10], but examples of polymorphisms maintained by this mechanism are rare. Here, we present evidence that a polymorphism in an enzyme gene in Drosophila melanogaster is maintained by such a trade-off. The mitochondrially localized aldehyde dehydrogenase in D. melanogaster has two important functions: detoxifying acetaldehyde derived from dietary ethanol [11] and detoxifying larger aldehydes produced as byproducts of oxidative phosphorylation [12]. A derived variant of the enzyme, Leu479Phe, is present in moderate frequencies in most temperate populations but is rare in more ethanol-averse tropical populations. Using purified recombinant protein, we show that the Leu-Phe substitution increases turnover rate of acetaldehyde but decreases turnover rate of larger aldehydes. Furthermore, using transgenic fly lines, we show that the substitution increases lifetime fitness on medium supplemented with an ecologically relevant ethanol concentration but decreases fitness on medium lacking ethanol. The strong, opposing selection pressures, coupled with documented highly variable ethanol concentrations in breeding sites of temperate populations, implicate an essential role for environmental heterogeneity in maintaining the polymorphism. •Breeding sites of Drosophila melanogaster contain variable levels of ethanol•One Aldehyde dehydrogenase allele is favored by high ethanol levels•The alternative allele is favored in flies not exposed to ethanol•As a result, a polymorphism is maintained in natural populations Chakraborty and Fry show that, in the fruit fly Drosophila melanogaster, a polymorphism in the enzyme gene Aldehyde dehydrogenase is maintained by conflicting selection pressures. One allele is advantageous in flies exposed to ethanol, a natural component of breeding sites, while the alternative allele is advantageous in the absence of ethanol.