Article

Deletion of a conserved regulatory element in the Drosophila Adh gene leads to increased alcohol dehydrogenase activity but also delays development.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Genetics (impact factor: 4.01). 10/2000; 156(1):219-27. pp.219-27
Source: PubMed

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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Keywords

3' UTR deletion
 
3' UTR sequence
 
Adh 3' UTR
 
ADH allozyme type
 
amino acid replacement
 
different types
 
enzymatic activity
 
experimental test
 
negative fitness effect
 
negative regulatory element
 
protein concentrations
 
regulatory changes
 
selective differences
 
transgenic experiments
 
two changes
 
two mechanisms
 
twofold increase
 
vivo Adh mRNA
 
vivo levels
 
well-known ADH-Slow