An Evolutionary Constraint: Strongly Disfavored Class of Change in DNA Sequence during Divergence of Cis-Regulatory Modules

An Evolutionary Constraint: Strongly Disfavored Class of Change in DNA Sequence during Divergence of Cis-Regulatory Modules

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...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 33; pp. 11769 - 11774
Main Authors: Cameron, R. Andrew, Chow, Suk Hen, Berney, Kevin, Chiu, Tsz-Yeung, Yuan, Qiu-Autumn, Krämer, Alexander, Helguero, Argelia, Ransick, Andrew, Yun, Mirong, Davidson, Eric H.
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 16-08-2005
National Acad Sciences
Subjects:
Animals
Base Sequence
Biological Sciences
Divergent evolution
DNA
DNA - genetics
Echinoidea
Environmental conservation
Evolution
Evolution, Molecular
Genes
Genomes
Genomics
Models, Genetic
Molecular Sequence Data
Open reading frames
Polymorphism, Single Nucleotide - genetics
Regulatory Sequences, Nucleic Acid - genetics
Sea Urchins - genetics
Sequencing
Strongylocentrotus franciscanus
Strongylocentrotus purpuratus
Transcription factors
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Summary: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 artifical 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.
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Author contributions: R.A.C. and E.H.D. designed research; R.A.C., S.H.C., K.B., T.-Y.C., Q.-A.Y., A.K., and A.H. performed research; A.R. contributed new reagents/analytic tools; R.A.C., E.H.D., and K. B. analyzed data; and R.A.C. and E.H.D. wrote the paper.
To whom correspondence should be addressed. E-mail: davidson@caltech.edu.
Contributed by Eric H. Davidson, June 23, 2005
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ088382–DQ088386).
Abbreviation: BAC, bacterial artificial chromosome.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0505291102