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

A colorful origin for the genetic code: Information theory, statistical mechanics and the emergence of molecular codes

The genetic code maps the sixty-four nucleotide triplets (codons) to twenty amino-acids. While the biochemical details of this code were unraveled long ago, its origin is still obscure. We review information-theoretic approaches to the problem of the code's origin and discuss the results of a recent work that treats the code in terms of an evolving, error-prone information channel. Our model - which utilizes the rate-distortion theory of noisy communication channels - suggests that the genetic code originated as a result of the interplay of the three conflicting evolutionary forces: the needs for diverse amino-acids, for error-tolerance and for minimal cost of resources. The description of the code as an information channel allows us to mathematically identify the fitness of the code and locate its emergence at a second-order phase transition when the mapping of codons to amino-acids becomes nonrandom. The noise in the channel brings about an error-graph, in which edges connect codons that are likely to be confused. The emergence of the code is governed by the topology of the error-graph, which determines the lowest modes of the graph-Laplacian and is related to the map coloring problem.Comment: In press. Keywords: Molecular codes; Origin of the genetic code; Biological information channels; Error-load; Fitness; Rate-distortion theory; Origin of lif

A model for the emergence of the genetic code as a transition in a noisy information channel

The genetic code maps the sixty-four nucleotide triplets (codons) to twenty amino-acids. Some argue that the specific form of the code with its twenty amino-acids might be a 'frozen accident' because of the overwhelming effects of any further change. Others see it as a consequence of primordial biochemical pathways and their evolution. Here we examine a scenario in which evolution drives the emergence of a genetic code by selecting for an amino-acid map that minimizes the impact of errors. We treat the stochastic mapping of codons to amino-acids as a noisy information channel with a natural fitness measure. Organisms compete by the fitness of their codes and, as a result, a genetic code emerges at a supercritical transition in the noisy channel, when the mapping of codons to amino-acids becomes nonrandom. At the phase transition, a small expansion is valid and the emergent code is governed by smooth modes of the Laplacian of errors. These modes are in turn governed by the topology of the error-graph, in which codons are connected if they are likely to be confused. This topology sets an upper bound - which is related to the classical map-coloring problem - on the number of possible amino-acids. The suggested scenario is generic and may describe a mechanism for the formation of other error-prone biological codes, such as the recognition of DNA sites by proteins in the transcription regulatory network.Comment: Keywords: genetic code, rate-distortion theory, biological information channel

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