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Cited by 88Genomics and Chromatin DynamicsGenomics and Phylogenetic StudiesChromosomal and Genetic Variations

Tracing the evolutionary history of Drosophila regulatory regions with models that identify transcription factor binding sites

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Dermitzakis, E. T.·2003·Molecular Biology and Evolution
DOI 10.1093/molbev/msg077
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Abstract

Much of evolutionary change is mediated at the level of gene expression, yet our understanding of regulatory evolution remains unsatisfying. In light of recent data indicating that transcription factor binding sites undergo substantial turnover between species, we attempt to quantify the process of binding site turnover in regulatory regions of well-studied genes controlling embryonic patterning in Drosophila. We examine polymorphism and divergence data in Drosophila melanogaster and four related species from regulatory regions of five early development genes for which functional binding sites have been identified. This analysis reveals that Drosophila regulatory regions exhibit patterns of variation consistent with functional constraint. We develop a novel approach to binding site prediction which we use to characterize the process of binding site divergence in regulatory regions. This method uses sets of known binding sites to construct a model that predicts transcription factor specificity and bootstrap sampling to derive significance levels. This approach allows appropriate significance levels to be determined even in the face of skewed base composition in the background sequence. Using this approach, we show that, although functional elements exhibit conservation of sequence, there is substantial potential to gain new functional elements within the regulatory regions. Our results show that application of models that predict transcription factor binding sites can yield insights into the process and dynamics of binding site evolution within regulatory regions.

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  • The arrangement, spacing, and number of target sites are relatively insignificant.

    “The arrangement, spacing, and number of these sites is relatively insignificant (Balhoff and Wray, 2005; Cameron and Davidson, 2009; Dermitzakis et al., 2003; Liberman and Stathopoulos, 2009; Ludwig et al., 2000; Walters et al., 2008).”

    From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Dermitzakis et al., 2003

    The Introduction says regulatory function can persist despite structural reorganization caused by binding-site gains and losses. The section “Predicting the Pattern of Binding Site Evolution” similarly suggests that some predicted sites can be gained or lost without strong effects on gene regulation. Neither passage establishes that site arrangement, spacing, and number are generally insignificant; the latter finding is limited to predicted sites with less essential roles. (LLM, conf=0.86)

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Authors
Dermitzakis, E. T.
Affiliations
Pennsylvania State University (US)
Corresponding author
Dermitzakis, E. T.
ORCID
Dermitzakis, E. T.
Venue
Molecular Biology and Evolution
Publisher
Oxford University Press (OUP)
Published
2003-04-02
Volume
20
Issue
5
Pages
703-714
ISSN
  • 0737-4038 (ISSN-L)
  • 1537-1719
DOI
10.1093/molbev/msg077
OpenAlex
W1994190548
Cited by
88
References
51
Citations by year
2024: 2 · 2023: 2 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 1
FWCI
3.68
Type
journal article
Language
en
Open access
Locations
  • Molecular Biology and Evolution (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
transcription factor binding sites, regulatory evolution, Drosophila, regulatory elements, binding site prediction, transcription factor specificity, functional constraints, sequence divergence, polymorphism, base composition bias
MeSH terms
Animals, Base Sequence, Binding Sites, Drosophila, Genes, Regulator, Models, Genetic, Molecular Sequence Data, Polymorphism, Genetic, Likelihood Functions, Sequence Alignment, Sequence Analysis, DNA, Evolution, Molecular, Databases, Nucleic Acid

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