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An evolutionary constraint: Strongly disfavored class of change in DNA sequence during divergence of cis-regulatory modules

Cameron, R. Andrew and Chow, Suk Hen and Berney, Kevin and Chiu, Tsz-Yeung and Yuan, Qiu-Autumn and Krämer, Alexander and Helguero, Argelia and Ransick, Andrew and Yun, Mirong and Davidson, Eric H. (2005) An evolutionary constraint: Strongly disfavored class of change in DNA sequence during divergence of cis-regulatory modules. Proceedings of the National Academy of Sciences of the United States of America, 102 (33). pp. 11769-11774. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:CAMpnas05

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Abstract

The DNA of functional cis-regulatory modules displays extensive sequence conservation in comparisons of genomes from modestly distant species. Patches of sequence that are several hundred base pairs in length within these modules are often seen to be 80-95% identical, although the flanking sequence cannot even be aligned. However, it is unlikely that base pairs located between the transcription factor target sites of cis-regulatory modules have sequence-dependent function, and the mechanism that constrains evolutionary change within cis-regulatory modules is incompletely understood. We chose five functionally characterized cis-regulatory modules from the Strongylocentrotus purpuratus (sea urchin) genome and obtained orthologous regulatory and flanking sequences from a bacterial artificial chromosome genome library of a congener, Strongylocentrotus franciscanus. As expected, single-nucleotide substitutions and small indels occur freely at many positions within the regulatory modules of these two species, as they do outside the regulatory modules. However, large indels (> 20 bp) are statistically almost absent within the regulatory modules, although they are common in flanking intergenic or intronic sequence. The result helps to explain the patterns of evolutionary sequence divergence characteristic of cis-regulatory DNA.


Item Type:Article
Additional Information:Copyright © 2005 by the National Academy of Sciences. Contributed by Eric H. Davidson, June 23, 2005. We thank Applied Biosystems for their support. This work was also supported by National Science Foundation Grant IOB-0212869 and the California Institute of Technology Beckman Institute. Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ088382–DQ088386).
Subject Keywords:genomic sequence conservation, indels, regulatory evolution, sea-urchin embryo, non-repetitive DNA, functional-analysis, gene network, human genome, Endo16 gene, SCL loci, organization, conservation, expression
Record Number:CaltechAUTHORS:CAMpnas05
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:CAMpnas05
Alternative URL:http://dx.doi.org/10.1073/pnas.0505291102
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:912
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:15 Feb 2006
Last Modified:26 Dec 2012 08:42

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