Biology
Document Type
Article
Abstract
It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox) genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by an extensive array of cis-regulatory modules (CRMs). How the regulatory modules functionally evolve in different species is not clear. A comparison of the CRMs for the Abdominal-B gene from different Drosophila species reveals relatively low levels of overall sequence conservation. However, embryonic enhancer CRMs from other Drosophila species direct transgenic reporter gene expression in the same spatial and temporal patterns during development as their D. melanogaster orthologs. Bioinformatic analysis reveals the presence of short conserved sequences within defined CRMs, representing gap and pair-rule transcription factor binding sites. One predicted binding site for the gap transcription factor KRUPPEL in the IAB5 CRM was found to be altered in Superabdominal (Sab) mutations. In Sab mutant flies, the third abdominal segment is transformed into a copy of the fifth abdominal segment. A model for KRUPPEL-mediated repression at this binding site is presented. These findings challenge our current understanding of the relationship between sequence evolution at the molecular level and functional activity of a CRM. While the overall sequence conservation at Drosophila CRMs is not distinctive from neighboring genomic regions, functionally critical transcription factor binding sites within embryonic enhancer CRMs are highly conserved. These results have implications for understanding mechanisms of gene expression during embryonic development, enhancer function, and the molecular evolution of eukaryotic regulatory modules. © 2009 Ho et al.
Publication Title
PLoS Genetics
Publication Date
11-1-2009
Volume
5
Issue
11
ISSN
1553-7390
DOI
10.1371/journal.pgen.1000709
Keywords
Drosophila melanogaster; Eukaryota, gene expression
Repository Citation
Ho, Margaret C.W.; Johnsen, Holly; Goetz, Sara E.; Schiller, Benjamin J.; Bae, Esther; Tran, Diana A.; Shur, Andrey S.; Allen, John M.; Rau, Christoph; Bender, Welcome; Fisher, William W.; Celniker, Susan E.; and Drewell, Robert A., "Functional evolution of cis-regulatory modules at a homeotic gene in Drosophila" (2009). Biology. 145.
https://commons.clarku.edu/faculty_biology/145
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Copyright Conditions
Ho, M. C., Johnsen, H., Goetz, S. E., Schiller, B. J., Bae, E., Tran, D. A., ... & Drewell, R. A. (2009). Functional evolution of cis-regulatory modules at a homeotic gene in Drosophila. PLoS genetics, 5(11), e1000709.
