DNA information: from digital code to analogue structure

Travers, Andrew; Muskhelishvili, Georgi; Thompson, J. M. T.

doi:10.1098/rsta.2011.0231

Cited by 41 publications

(36 citation statements)

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“…Since both these information types are inscribed in the same DNA sequence, and yet one is discrete whereas the other is continuous, they have been respectively dubbed the digital and analog DNA codes (Marr et al 2008;Travers et al 2012;Muskhelishvili and Travers 2013). The potential of the DNA to adopt distinct configurations is strongly modulated by DNA supercoiling, which is increasingly recognized as one of the major forces coordinating the cellular DNA transactions in both prokaryotes (including Archaea) and eukaryotes.…”

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confidence: 99%

“…Again, the DNA in small circles has higher configurational entropy than in larger circles, which accommodate writhing by adopting a plectonemic form (Mitchell and Harris 2013). DNA supercoiling may thus affect the number of configurations adopted by the DNA (Irobalieva et al 2015), or the volume of the configurational space (Bednar et al 1994;Travers et al 2012). In other words, the repertoire of possible local structures will depend on the superhelical state of the DNA and the sign (either negative or positive) of coiling.…”

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The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

Muskhelishvili

Travers

2016

Biophys Rev

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We argue that dynamic changes in DNA supercoiling in vivo determine both how DNA is packaged and how it is accessed for transcription and for other manipulations such as recombination. In both bacteria and eukaryotes, the principal generators of DNA superhelicity are DNA translocases, supplemented in bacteria by DNA gyrase. By generating gradients of superhelicity upstream and downstream of their site of activity, translocases enable the differential binding of proteins which preferentially interact with respectively more untwisted or more writhed DNA. Such preferences enable, in principle, the sequential binding of different classes of protein and so constitute an essential driver of chromatin organization.Keywords DNA supercoiling . DNA translocases . Chromatin organization . Superhelicity gradients . DNA untwisting . DNAwrithing Dynamic changes of DNA supercoiling act as a driving force behind the alterations of genetic activity and DNA compaction both in eukaryotes and prokaryotes. Both these processes involve formation of spatially organized nucleoprotein structures by DNA architectural proteins. Whereas in eukaryotes the paradigmal example is the histone octamer, in prokaryotes a similar function is attributed to a small class of highly abundant nucleoid-associated proteins. We argue that, depending on the primary sequence organization, the changes of superhelicity elicit various alterations of local DNA geometry, while these, in turn, facilitate the assembly of distinct nucleoprotein structures pertinent to genetic function. Genome-wide conversion of the superhelical energy into various three-dimensional DNA structures thus acts as an analogue code coordinating the energy supply with the genetic expression of the chromosome.Recent studies make it increasingly clear that the DNA double helix carries at least two types of encoded information and that these include the well-known genetic code and the structural information determining the form and physical properties of the double helix itself. Since both these information types are inscribed in the same DNA sequence, and yet one is discrete whereas the other is continuous, they have been respectively dubbed the digital and analog DNA codes (Marr et al. 2008;Travers et al. 2012;Muskhelishvili and Travers 2013). The potential of the DNA to adopt distinct configurations is strongly modulated by DNA supercoiling, which is increasingly recognized as one of the major forces coordinating the cellular DNA transactions in both prokaryotes (including Archaea) and eukaryotes.DNA supercoiling can be generated by the simple application of torque to the double helix (Strick et al. 1998) but, importantly, because the DNA molecule itself possesses chirality-it is, after all, a right-handed double helix-the local structures stabilized by changes in superhelical density depend on both the sign and strength of the applied torque. For example, both positive and negative torque (respectively overand underwinding of the double helix) can change the intrinsic coiling of ...

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The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

Muskhelishvili

Travers

2016

Biophys Rev

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“…This is the case of embryology-that is, the attainment of complex shaped organisms from embryonal stages. There are cases, though, where genetic information can be related directly to the structural properties of nucleic acids [4]. Also, in the template-guided protein synthesis, the nucleotide sequence that determines the amino acid chain can also influence the secondary and tertiary structures of proteins through mechanisms still not completely understood [5,6].…”

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confidence: 99%

DNA, dichotomic classes and frame synchronization: a quasi-crystal framework

Giannerini

González

Rosa

2012

Phil. Trans. R. Soc. A.

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In this article, we show how a new mathematical model of the genetic code can be exploited for investigating the almost periodic properties of DNA and mRNA protein-coding sequences. We present the main mathematical features of the model and highlight its connections with both number theory and group theory. The group theoretic framework presents interesting analogies with the theory of crystals. Moreover, we exploit the information provided by dichotomic classes, binary variables naturally derived from the mathematical model, in order to build statistical classifiers for retrieving and predicting the normal reading frame used by the ribosome in protein synthesis. The results show that coding sequences possess a local informational structure that can be related to frame synchronization processes. The information for retrieving the normal reading frame, which implies the existence of short-range correlations and almost periodic structures related to the organization of codons, offers an interesting analogy with the properties of quasi-crystals. From a theoretical point of view, our results might contribute to clarifying the relation between biological information and shape in nucleic acids and proteins. Also, from the point of view of applications, we present new promising tools for designing efficient algorithms for frame synchronization, which plays a crucial role in faithful synthesis of proteins.

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“…The results of a wide range of our own investigations over the last years have their foundations in statistical physics and information theory [2,4,[25][26][27][28][29][30][31]. They have cemented the notion of a tight interplay of the regulatory network implemented via TFs and their binding sites (digital control); and the regulation implemented via alterations of chromosomal configuration and DNA compaction (analog control) in bacterial gene regulation (depicted in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Over the last ten years a wide range of studies provided first evidence that all these components are strongly interlinked and shape the observed gene expression patterns (see, e.g., [2][3][4]). The interplay of genome architecture and global regulators [5], the genome's spatiotemporal organization [6], as well as the relationship of sequence information and genome architecture [7] are challenging to understand.…”

Section: Introductionmentioning

confidence: 99%

Interplay of digital and analog control in time-resolved gene expression profiles

Beber

Sobetzko

Muskhelishvili

et al. 2016

EPJ Nonlinear Biomed Phys

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Background: Measuring the agreement between a gene expression profile and a known transcriptional regulatory network is an important step in the functional interpretation of bacterial physiological state. In this way, general design principles can be explored. One such interpretive framework is the relationship of digital control, that is, the impact of sequence-specific interactions, and analog control, i.e., the extent of the influence of chromosomal structure. Methods and Results:Here, we present time-resolved gene expression profiles of Escherichia coli's growth cycle as measured by RNA-seq. We extend methods which have been developed for discrete sets of differentially expressed genes and apply them to the wild type and two mutant time-series for which the global transcriptional regulators fis and hns were inactivated. We test our continuous methods using simulated 'expression profiles' generated from random Boolean network dynamics where we observe a clear trade-off between maximum response and level of detail included. In the real time-course expression data, we find strong interdependent changes of digital and analog control during the exponential growth phase and a dominance of analog control during the stationary phase. Conclusions: Our investigation puts forward a simple and reliable method for quantifying the match between time-resolved gene expression profiles and a transcriptional regulatory network. The method reveals a systematic compensatory interplay of digital and analog control in the genetic regulation of E. coli's growth cycle.

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DNA information: from digital code to analogue structure

Cited by 41 publications

References 117 publications

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

DNA, dichotomic classes and frame synchronization: a quasi-crystal framework

Interplay of digital and analog control in time-resolved gene expression profiles

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