Reference Report

Reference
Citation	Parsch, J., Russell, J.A., Beerman, I., Hartl, D.L., Stephan, W. (2000). Deletion of a conserved regulatory element in the Drosophila Adh gene leads to increased alcohol dehydrogenase activity but also delays development. Genetics 156(1): 219--227. (Export to RIS)
FlyBase ID	FBrf0130014
Publication Type	Research paper
PubMed ID	10978287
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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Language of Publication	English
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Publication Type	Journal
Abbreviation	Genetics
Title	Genetics
Publication Year	1916-
ISBN/ISSN	0016-6731
Data from Reference
Alleles (8)
	Adh^fn6 Adh^Wa-F.tCa Adh^{Wa-F.Δ1762-1769} Adh^Wa-S.tCa Adh^{Wa-S.Δ1762-1769} Adh^Wa-S gypsy\su(Hw)BR⁴³⁰ y^+mDint2
Constructs (4)
	P{Adh.Wa-F.Δ1762-1769} P{Adh.Wa-F} P{Adh.Wa-S.Δ1762-1769} P{Adh.Wa-S}
Genes (3)
	Adh gypsy\su(Hw)BR y