Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila Export

@article{citeulike:6082951, 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.}, author = {Ho, Margaret C. W. and Johnsen, Holly and Goetz, Sara E. and Schiller, Benjamin J. and Bae, Esther and Tran, Diana A. and Shur, Andrey S. and Allen, John M. and Rau, Christoph and Bender, Welcome and Fisher, William W. and Celniker, Susan E. and Drewell, Robert A.}, citeulike-article-id = {6082951}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pgen.1000709}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19893611}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19893611}, day = {6}, doi = {10.1371/journal.pgen.1000709}, issn = {1553-7404}, journal = {PLoS Genet}, keywords = {cis-regulatory, flies, hox\_genes}, month = {November}, number = {11}, pages = {e1000709+}, posted-at = {2009-11-07 14:07:43}, priority = {2}, publisher = {Public Library of Science}, title = {Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila}, url = {http://dx.doi.org/10.1371/journal.pgen.1000709}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:6082951 L3 - citeulike-article-id:6082951 N2 - 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. IS - 11 JF - PLoS Genet SN - 1553-7404 TI - Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila PB - Public Library of Science VL - 5 SP - e1000709 KW - cis-regulatory KW - flies KW - hox_genes AU - Ho, Margaret AU - Johnsen, Holly AU - Goetz, Sara AU - Schiller, Benjamin AU - Bae, Esther AU - Tran, Diana AU - Shur, Andrey AU - Allen, John AU - Rau, Christoph AU - Bender, Welcome AU - Fisher, William AU - Celniker, Susan AU - Drewell, Robert PY - 2009/11/06/ UR - http://dx.doi.org/10.1371/journal.pgen.1000709 ER -