Casting Polymer Nets to Optimize Noisy Molecular Codes

Life relies on the efficient performance of molecular codes, which relate symbols and meanings via error-prone molecular recognition. We describe how optimizing a code to withstand the impact of molecular recognition noise may be approximated by the statistics of a two-dimensional network made of polymers. The noisy code is defined by partitioning the space of symbols into regions according to their meanings. The "polymers" are the boundaries between these regions and their statistics defines the cost and the quality of the noisy code. When the parameters that control the cost-quality balance are varied, the polymer network undergoes a first-order transition, where the number of encoded meanings rises discontinuously. Effects of population dynamics on the evolution of molecular codes are discussed.Comment: PNAS 200

A simple model for the evolution of molecular codes driven by the interplay of accuracy, diversity and cost

Molecular codes translate information written in one type of molecules into another molecular language. We introduce a simple model that treats molecular codes as noisy information channels. An optimal code is a channel that conveys information accurately and efficiently while keeping down the impact of errors. The equipoise of the three conflicting needs, for minimal error-load, minimal cost of resources and maximal diversity of vocabulary, defines the fitness of the code. The model suggests a mechanism for the emergence of a code when evolution varies the parameters that control this equipoise and the mapping between the two molecular languages becomes non-random. This mechanism is demonstrated by a simple toy model that is formally equivalent to a mean-field Ising magnet.Comment: Keywords: molecular codes, rate-distortion theory, biological information channels, stochastic maps, genetic code, genetic network

A rate-distortion scenario for the emergence and evolution of noisy molecular codes

We discuss, in terms of rate-distortion theory, the fitness of molecular codes as the problem of designing an optimal information channel. The fitness is governed by an interplay between the cost and quality of the channel, which induces smoothness in the code. By incorporating this code fitness into population dynamics models, we suggest that the emergence and evolution of molecular codes may be explained by simple channel design considerations.Comment: PACS numbers: 87.10.+e, 87.14.Gg, 87.14.E

Molecular Recognition as an Information Channel: The Role of Conformational Changes

Molecular recognition, which is essential in processing information in biological systems, takes place in a crowded noisy biochemical environment and requires the recognition of a specific target within a background of various similar competing molecules. We consider molecular recognition as a transmission of information via a noisy channel and use this analogy to gain insights on the optimal, or fittest, molecular recognizer. We focus on the optimal structural properties of the molecules such as flexibility and conformation. We show that conformational changes upon binding, which often occur during molecular recognition, may optimize the detection performance of the recognizer. We thus suggest a generic design principle termed 'conformational proofreading' in which deformation enhances detection. We evaluate the optimal flexibility of the molecular recognizer, which is analogous to the stochasticity in a decision unit. In some scenarios, a flexible recognizer, i.e., a stochastic decision unit, performs better than a rigid, deterministic one. As a biological example, we discuss conformational changes during homologous recombination, the process of genetic exchange between two DNA strands.Comment: Keywords--Molecular information channels, molecular recognition, conformational proofreading. http://www.weizmann.ac.il/complex/tlusty/papers/IEEE2009b.pd

High fidelity of RecA-catalyzed recombination: a watchdog of genetic diversity

Homologous recombination plays a key role in generating genetic diversity, while maintaining protein functionality. The mechanisms by which RecA enables a single-stranded segment of DNA to recognize a homologous tract within a whole genome are poorly understood. The scale by which homology recognition takes place is of a few tens of base pairs, after which the quest for homology is over. To study the mechanism of homology recognition, RecA-promoted homologous recombination between short DNA oligomers with different degrees of heterology was studied in vitro, using fluorescence resonant energy transfer. RecA can detect single mismatches at the initial stages of recombination, and the efficiency of recombination is strongly dependent on the location and distribution of mismatches. Mismatches near the 5' end of the incoming strand have a minute effect, whereas mismatches near the 3' end hinder strand exchange dramatically. There is a characteristic DNA length above which the sensitivity to heterology decreases sharply. Experiments with competitor sequences with varying degrees of homology yield information about the process of homology search and synapse lifetime. The exquisite sensitivity to mismatches and the directionality in the exchange process support a mechanism for homology recognition that can be modeled as a kinetic proofreading cascade.Comment: http://www.weizmann.ac.il/complex/tlusty/papers/NuclAcidRes2006.pdf http://nar.oxfordjournals.org/cgi/content/short/34/18/502

Coding limits on the number of transcription factors

Transcription factor proteins bind specific DNA sequences to control the expression of genes. They contain DNA binding domains which belong to several super-families, each with a specific mechanism of DNA binding. The total number of transcription factors encoded in a genome increases with the number of genes in the genome. Here, we examined the number of transcription factors from each super-family in diverse organisms. We find that the number of transcription factors from most super-families appears to be bounded. For example, the number of winged helix factors does not generally exceed 300, even in very large genomes. The magnitude of the maximal number of transcription factors from each super-family seems to correlate with the number of DNA bases effectively recognized by the binding mechanism of that super-family. Coding theory predicts that such upper bounds on the number of transcription factors should exist, in order to minimize cross-binding errors between transcription factors. This theory further predicts that factors with similar binding sequences should tend to have similar biological effect, so that errors based on mis-recognition are minimal. We present evidence that transcription factors with similar binding sequences tend to regulate genes with similar biological functions, supporting this prediction. The present study suggests limits on the transcription factor repertoire of cells, and suggests coding constraints that might apply more generally to the mapping between binding sites and biological function.Comment: http://www.weizmann.ac.il/complex/tlusty/papers/BMCGenomics2006.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590034/ http://www.biomedcentral.com/1471-2164/7/23