Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

Kirchhamer, Carmen V.; Yuh, Chiou-Hwa; Davidson, Eric H.

doi:10.1073/pnas.93.18.9322

Cited by 100 publications

(49 citation statements)

References 70 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…humans. Although regulatory modules are often on the order of 1 kb, numerous developmental regulatory modules in mouse and Drosophila are as small as 100 bp (Kirchhamer et al 1996). I chose to model 100-bp enhancers as these are large enough to allow an investigation of the dynamics of turnover and are easily visualized and efficiently simulated (simulations of 500-bp enhancers yield similar results; not shown).…”

Section: Resultsmentioning

confidence: 99%

Changes in Selective Effects Over Time Facilitate Turnover of Enhancer Sequences

Bullaughey

2011

Genetics

View full text Add to dashboard Cite

Correct gene expression is often critical and consequently stabilizing selection on expression is widespread. Yet few genes possess highly conserved regulatory DNA, and for the few enhancers that have been carefully characterized, substantial functional reorganization has often occurred. Given that natural selection removes mutations of even very small deleterious effect, how can transcription factor binding evolve so readily when it underlies a conserved phenotype? As a first step toward addressing this question, I combine a computational model for regulatory function that incorporates many aspects of our present biological knowledge with a model for the fitness effects of misexpression. I then use this model to study the evolution of enhancers. Several robust behaviors emerge: First, the selective effects of mutations at a site change dramatically over time due to substitutions elsewhere in the enhancer, and even the overall degree of constraint across the enhancer can change considerably. Second, many of the substitutions responsible for changes in binding occur at sites where previously the mutation would have been strongly deleterious, suggesting that fluctuations in selective effects at a site are important for functional turnover. Third, most substitutions contributing to the repatterning of binding and constraint are effectively neutral, highlighting the importance of genetic drift-even for enhancers underlying conserved phenotypes. These findings have important implications for phylogenetic inference of function and for interpretations of selection coefficients estimated for regulatory DNA.

show abstract

Section: Resultsmentioning

confidence: 99%

Changes in Selective Effects Over Time Facilitate Turnover of Enhancer Sequences

Bullaughey

2011

Genetics

View full text Add to dashboard Cite

show abstract

“…expression in different tissues and at different times during development, each of which may be controlled by different DNA regulatory elements. Several studies have shown that this is the case (Hughes 1994;Kirchhamer et al 1996;Arnone and Davidson 1997). If duplicate genes lose different regulatory subfunctions, each affecting different spatial and/or temporal expression patterns, then they must complement each other by jointly retaining the full set of subfunctions present in the ancestral gene.…”

Section: Redundancy or Functional Divergence?mentioning

confidence: 99%

The Ghost of Selection Past: Rates of Evolution and Functional Divergence of Anciently Duplicated Genes

Peer

Taylor

Braasch

et al. 2001

Journal of Molecular Evolution

165

106

View full text Add to dashboard Cite

Abstract. The duplication of genes and even complete genomes may be a prerequisite for major evolutionary transitions and the origin of evolutionary novelties. However, the evolutionary mechanisms of gene evolution and the origin of novel gene functions after gene duplication have been a subject of many debates. Recently, we compiled 26 groups of orthologous genes, which included one gene from human, mouse, and chicken, one or two genes from the tetraploid Xenopus and two genes from zebrafish. Comparative analysis and mapping data showed that these pairs of zebrafish genes were probably produced during a fish-specific genome duplication that occurred between 300 and 450 Mya, before the teleost radiation (Taylor et al. 2001). As discussed here, many of these retained duplicated genes code for DNA binding proteins. Different models have been developed to explain the retention of duplicated genes and in particular the subfunctionalization model of Force et al. (1999) could explain why so many developmental control genes have been retained. Other models are harder to reconcile with this particular set of duplicated genes. Most genes seem to have been subjected to strong purifying selection, keeping properties such as charge and polarity the same in both duplicates, although some evidence was found for positive Darwinian selection, in particular for Hox genes. However, since only the cumulative pattern of nucleotide substitutions can be studied, clear indications of positive Darwinian selection or neutrality may be hard to find for such anciently duplicated genes. Nevertheless, an increase in evolutionary rate in about half of the duplicated genes seems to suggest that either positive Darwinian selection has occurred or that functional constraints have been relaxed at one point in time during functional divergence.

show abstract

“…The Mediator complex facilitates interactions between the enhancer and chromatin-modifying enzymes, such as histone acetyltransferases and nucleosome remodeling factors, to establish a chromatin environment that facilitates transcription of the target gene (see Box 1). By contrast, repressors may disrupt enhancer functional activity in one of two ways: (1) competition, where the binding sites for repressors and activators within an enhancer sequence overlap and, as a result, repressor binding excludes activators; and (2) quenching, in which repressors are able to inhibit the regulatory activity of activators bound to nearby sites within the enhancer (Gray et al, 1994;Kirchhamer et al, 1996;Levine and Manley, 1989;Small et al, 1991b).…”

Section: The Building Blocks Of Gene Regulation: the Functional Charamentioning

confidence: 99%

Dissecting the regulatory switches of development: lessons from enhancer evolution in Drosophila

Borok

Tran

et al. 2010

Development

View full text Add to dashboard Cite

SummaryCis-regulatory modules are non-protein-coding regions of DNA essential for the control of gene expression. One class of regulatory modules is embryonic enhancers, which drive gene expression during development as a result of transcription factor protein binding at the enhancer sequences. Recent comparative studies have begun to investigate the evolution of the sequence architecture within enhancers. These analyses are illuminating the way that developmental biologists think about enhancers by revealing their molecular mechanism of function.

show abstract

Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

Cited by 100 publications

References 70 publications

Changes in Selective Effects Over Time Facilitate Turnover of Enhancer Sequences

Changes in Selective Effects Over Time Facilitate Turnover of Enhancer Sequences

The Ghost of Selection Past: Rates of Evolution and Functional Divergence of Anciently Duplicated Genes

Dissecting the regulatory switches of development: lessons from enhancer evolution in Drosophila

Contact Info

Product

Resources

About