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Deletion of a Conserved Regulatory Element in the Drosophila Adh Gene Leads to Increased Alcohol Dehydrogenase Activity but Also Delays Development
Journal article   Open access   Peer reviewed

Deletion of a Conserved Regulatory Element in the Drosophila Adh Gene Leads to Increased Alcohol Dehydrogenase Activity but Also Delays Development

John Parsch, Jacob A Russell, Isabel Beerman, Daniel L Hartl and Wolfgang Stephan
Genetics (Austin), v 156(1), pp 219-227
01 Sep 2000
PMID: 10978287
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1461225View
Published, Version of Record (VoR) Open Open Access (License Unspecified)

Abstract

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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Genetics & Heredity
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