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

Journal Article · · PLoS Genetics
 [1];  [2];  [2];  [2];  [3];  [2];  [2];  [2];  [2];  [4];  [5];  [5];  [2]
  1. Harvey Mudd College, Claremont, CA (United States). Biology Dept.; DOE/OSTI
  2. Harvey Mudd College, Claremont, CA (United States). Biology Dept.
  3. Western Univ. of Health Sciences, Pomona, CA (United States). College of Osteopathic Medicine of the Pacific
  4. Harvard Medical School, Boston, MA (United States). Dept. of Biological Chemistry and Molecular Pharmacology
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Berkeley Drosophila Genome Project
+ Show Author Affiliations
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.
Research Organization:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
Howard Hughes Medical Institute; National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1627279
Journal Information:
PLoS Genetics, Journal Name: PLoS Genetics Journal Issue: 11 Vol. 5; ISSN 1553-7404
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (14)

Chromosomal organization at the level of gene complexes journal November 2010
The open for business model of the bithorax complex in Drosophila journal June 2015
The developmental transcriptome of Drosophila melanogaster journal December 2010
Flanking sequence context-dependent transcription factor binding in early Drosophila development journal January 2013
Functionally conserved enhancers with divergent sequences in distant vertebrates journal October 2015
Tempo and Mode in Evolution of Transcriptional Regulation journal January 2012
Pervasive Divergence of Transcriptional Gene Regulation in Caenorhabditis Nematodes journal June 2014
Disruption of the Abdominal-B Promoter Tethering Element Results in a Loss of Long-Range Enhancer-Directed Hox Gene Expression in Drosophila journal January 2011
Microevolution of cis-Regulatory Elements: An Example from the Pair-Rule Segmentation Gene fushi tarazu in the Drosophila melanogaster Subgroup journal November 2011
Transcription Factor Binding Site Redundancy in Embryonic Enhancers of the Drosophila Bithorax Complex journal December 2011
Drosophila relics hobo and hobo-MITEs transposons as raw material for new regulatory networks journal January 2018
Nucleotide Interdependency in Transcription Factor Binding Sites in theDrosophilaGenome journal January 2016
A homeotic shift late in development drives mimetic color variation in a bumble bee journal May 2019
Transposable elements are the primary source of novelty in primate gene regulation journal August 2017

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