title: An evolutionary constraint: strongly disfavored class of change in DNA sequence during divergence of cis-regulatory modules.
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.
authors.affiliation: Division of Biology and Center for Computational Regulatory Genomics of the Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Cameron
authors.forename: Suk Hen
authors.initials: SH
authors.lastname: Chow
authors.forename: Kevin
authors.initials: K
authors.lastname: Berney
authors.forename: Tsz-Yeung
authors.initials: TY
authors.lastname: Chiu
authors.forename: Qiu-Autumn
authors.initials: QA
authors.lastname: Yuan
authors.forename: Alexander
authors.initials: A
authors.lastname: Krämer
authors.forename: Argelia
authors.initials: A
authors.lastname: Helguero
authors.forename: Andrew
authors.initials: A
authors.lastname: Ransick
authors.forename: Mirong
authors.initials: M
authors.lastname: Yun
authors.forename: Eric H
authors.initials: EH
authors.lastname: Davidson
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D019143:Evolution, Molecular; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012617:Sea Urchins / Q000235:genetics
chemical_list: D004247:DNA