Open AccessDeletion of a Conserved Regulatory Element in the Drosophila Adh Gene Leads to Increased Alcohol Dehydrogenase Activity but Also Delays Development
Author(s) -
John Parsch,
Jacob A. Russell,
Isabel Beerman,
Daniel L. Hartl,
Wolfgang Stephan
Publication year - 2000
Publication title -
genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.792
H-Index - 246
eISSN - 1943-2631
pISSN - 0016-6731
DOI - 10.1093/genetics/156.1.219
Subject(s) - alcohol dehydrogenase , biology , drosophila melanogaster , genetics , untranslated region , gene , negative selection , enzyme , conserved sequence , natural selection , amino acid , biochemistry , peptide sequence , selection (genetic algorithm) , messenger rna , genome , artificial intelligence , computer science
In vivo levels of enzymatic activity may be increased through either structural or regulatory changes. Here we use Drosophila melanogaster alcohol dehydrogenase (ADH) in an experimental test for selective differences between these two mechanisms. The well-known ADH-Slow (S)/Fast (F) amino acid replacement leads to a twofold increase in activity by increasing the catalytic efficiency of the enzyme. Disruption of a highly conserved, negative regulatory element in the Adh 3' UTR also leads to a twofold increase in activity, although this is achieved by increasing in vivo Adh mRNA and protein concentrations. These two changes appear to be under different types of selection, with positive selection favoring the amino acid replacement and purifying selection maintaining the 3' UTR sequence. Using transgenic experiments we show that deletion of the conserved 3' UTR element increases adult and larval Adh expression in both the ADH-F and ADH-S genetic backgrounds. However, the 3' UTR deletion also leads to a significant increase in developmental time in both backgrounds. ADH allozyme type has no detectable effect on development. These results demonstrate a negative fitness effect associated with Adh overexpression. This provides a mechanism whereby natural selection can discriminate between alternative pathways of increasing enzymatic activity.