Quantitative specificity of the Mnt repressor

Fields, Dana S.; He, Yanping; Al-Uzri, Ahmed Y; Stormo, Gary D.

doi:10.1006/jmbi.1997.1171

Cited by 82 publications

(95 citation statements)

References 41 publications

(49 reference statements)

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“…The decrease of binding efficiency was ascribed to the base cooperation effect, since when combined with a different nucleotide, neither of the two bases composing the original nucleotide pair interfered with the DNA binding. A similar effect was noticed previously in other systems [7][8][9][10].…”

Section: Introductionsupporting

confidence: 90%

The binding of fork head proteins to DNA is partly determined by cooperation of bases

Mach

2006

Open Life Sciences

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Our previous study revealed that DNA recognition by the insect Fork head transcription factors depends on specific combinations of neighboring bases, a phenomenon called the base cooperation effect. This study presents a simple algorithm designed for in silico investigation of the base cooperation effect. The algorithm measures and evaluates observed and expected frequencies of various base combinations within a set of aligned binding sites. Consequently, statistically significant differences between the observed and expected frequencies are interpreted as evidence of either positive or negative base cooperation effect. Our current results suggest that the base cooperation affects DNA binding of the vertebrate members of the Fork head family, similarly to their insect homologies.

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Section: Introductionsupporting

confidence: 90%

The binding of fork head proteins to DNA is partly determined by cooperation of bases

Mach

2006

Open Life Sciences

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“…Multiple empirical studies involving single-base changes in TFBSs suggest an average energetic cost of a mismatch of β ' 2:0 (Table 1). Numerous studies also support the additivity assumption as a first-order approximation (16)(17)(18)(19)(20), although higher-order effects involving TFBS shape can also contribute to the overall binding energy (21). Eq.…”

Section: Significancementioning

confidence: 92%

Evolutionary meandering of intermolecular interactions along the drift barrier

Lynch¹,

Hagner

2014

Proc. Natl. Acad. Sci. U.S.A.

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Many cellular functions depend on highly specific intermolecular interactions, for example transcription factors and their DNA binding sites, microRNAs and their RNA binding sites, the interfaces between heterodimeric protein molecules, the stems in RNA molecules, and kinases and their response regulators in signaltransduction systems. Despite the need for complementarity between interacting partners, such pairwise systems seem to be capable of high levels of evolutionary divergence, even when subject to strong selection. Such behavior is a consequence of the diminishing advantages of increasing binding affinity between partners, the multiplicity of evolutionary pathways between selectively equivalent alternatives, and the stochastic nature of evolutionary processes. Because mutation pressure toward reduced affinity conflicts with selective pressure for greater interaction, situations can arise in which the expected distribution of the degree of matching between interacting partners is bimodal, even in the face of constant selection. Although biomolecules with larger numbers of interacting partners are subject to increased levels of evolutionary conservation, their more numerous partners need not converge on a single sequence motif or be increasingly constrained in more complex systems. These results suggest that most phylogenetic differences in the sequences of binding interfaces are not the result of adaptive fine tuning but a simple consequence of random genetic drift. cellular evolution | molecular interaction | transcription | random genetic drift | coevolution M uch of biology relies on the specificity of intermolecular interactions-the regulation of gene expression, the transmission of information via signal transduction, the assembly of monomeric subunits into multimers, vesicle sorting in eukaryotic cells, toxin-antitoxin systems in microbes, mating-type recognition, and many other cellular features. Although the basic structural features of such fitness-related traits would seem to be under strong purifying selection, molecular specificity often seems to be highly flexible in evolutionary time. For example, transcription-factor binding-site motifs often vary dramatically among orthologous genes in different species and even among similarly regulated genes within the same species (1-3). The binding interfaces of multimeric proteins can vary substantially among species, sometimes with no overlap at all (4, 5). The key amino acid sequences involved in intermolecular cross-talk in signal-transduction systems can evolve at high rates (6, 7), and growing evidence suggests that the locations of sites involved in posttranslational modification in individual proteins are under much weaker selective constraints than their absolute numbers (8). Although it is often argued that subtle differences in the motifs involved in intermolecular interactions are molded by the demands of natural selection, seldom has any direct evidence ever been provided in support of such arguments.The theory provided below makes the case...

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“…Regulatory fitness effects follow from the expression level of the regulated gene, which in turn depends on the relevant binding sites through the binding probability of the corresponding transcription factor (8,13). The factor-binding energy is often nearly additive in the nucleotide positions (21). The individual contributions i (a) can be inferred in an approximate way from the position weight matrix (20,22) (up to an overall constant 0 ),…”

Section: Q͑a͒ [4]mentioning

confidence: 99%

Evolutionary population genetics of promoters: Predicting binding sites and functional phylogenies

Mustonen

Lässig

2005

Proc. Natl. Acad. Sci. U.S.A.

107

125

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We study the evolution of transcription factor-binding sites in prokaryotes, using an empirically grounded model with point mutations and genetic drift. Selection acts on the site sequence via its binding affinity to the corresponding transcription factor. Calibrating the model with populations of functional binding sites, we verify this form of selection and show that typical sites are under substantial selection pressure for functionality: for cAMP response protein sites in Escherichia coli, the product of fitness difference and effective population size takes values 2N⌬F of order 10. We apply this model to cross-species comparisons of binding sites in bacteria and obtain a prediction method for binding sites that uses evolutionary information in a quantitative way. At the same time, this method predicts the functional histories of orthologous sites in a phylogeny, evaluating the likelihood for conservation or loss or gain of function during evolution. We have performed, as an example, a cross-species analysis of E. coli, Salmonella typhimurium, and Yersinia pseudotuberculosis. Detailed lists of predicted sites and their functional phylogenies are available.R egulatory interactions between genes are believed to provide an important mode of evolution, which accounts for a substantial part of the differentiation between species (1). This is reflected by the sequence variability of regulatory DNA: there is ample case evidence of compensatory evolution at conserved function but also of rapid functional changes even between closely related species (2). Lacking a quantitative model of regulatory evolution, however, alignments of regulatory sequences and predictions of their functionality have proven notoriously difficult.A large body of existing work has focused on the identification of transcription factor-binding sites as the main functional elements of regulatory DNA. For factors with known binding specificity (given in the form of a position weight matrix), putative binding sites are identified from their conservation in cross-species comparisons. Different measures of conservation have been introduced, which involve, e.g., the sequence similarity of aligned loci or their independent high scoring in all species compared (3-7). These methods are powerful prediction tools for binding sites. From an evolutionary point of view, however, the conservation criteria are heuristic. Hence, it is difficult to quantify the statistical significance of the results, which depends on the number and evolutionary distance of the species compared. Sequence conservation tends to be too restrictive in cases where substantial sequence variation is compatible with the position weight matrix, in particular for distant species. Simple sequence similarity measures implicitly assume neutral evolution, whereas independent scoring of orthologous sites ignores the evolutionary link between the species altogether. Most importantly, none of these conservation measures allows a consistent statistical treatment of functional innovations in the e...

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Quantitative specificity of the Mnt repressor

Cited by 82 publications

References 41 publications

The binding of fork head proteins to DNA is partly determined by cooperation of bases

The binding of fork head proteins to DNA is partly determined by cooperation of bases

Evolutionary meandering of intermolecular interactions along the drift barrier

Evolutionary population genetics of promoters: Predicting binding sites and functional phylogenies

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