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Collective properties of evolving populations of RNA molecules

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Abstract Book of the XXIII IUPAP International Conference on Statistical Physics, Genova, Italy, (9-13 July 2007)

Abstract

At early stages of biochemical evolution, the complexity of replicating molecules was limited by high mutation rates. In the framework of the RNA world hypothesis for the origin of life, small replicating RNA molecules are at the same time carriers of the genetic information and responsible for the biochemical function of the molecules. Therefore, RNA molecules, through their dual appearance as sequence of nucleotides and spatially folded, three-dimensional structure, represent a suitable model to study evolution of biological function 1. Due to a relatively high mutation rate, a population of RNA molecules consists of a large number of different sequences, commonly denoted as quasispecies. The essential ingredient in this model is the differentiation between genotype (molecular sequences which are affected by mutation) and phenotype (molecular structure, affected by selection). This framework allows a quantitative analysis of organizational properties of quasispecies as they adapt to different environments, such as their robustness, the effect of the degeneration of the sequence space, or the adaptation under different mutation rates and the error threshold associated. With help of large-scale numerical simulations, we investigate the structural properties of molecular quasispecies adapting to different environments both during the transient time before adaptation takes place and in the asymptotic state, once optimization has occurred 2. We observe a minimum in the adaptation time at values of the mutation rate relatively far from the error threshold. The optimal value results from a trade-off between diversity generation and fixation of advantageous mutants. We introduce and discuss different quantities describing the collective state of the population in the asymptotic regime, such as consensus sequence and structure of the consensus sequence. Through the definition of a consensus structure, it is shown that the quasispecies retains relevant structural information in a distributed fashion even above the error threshold, hence providing structural robustness to the population. Changing the system parameters (mutation rate, selective pressure, population size, sequence length), we characterize the collective properties of the population more in detail. Our results indicate that certain functional motifs of RNA secondary structure that withstand high mutation rates (as the ubiquitous hairpin motif) might appear early in evolution of life on Earth and be actually frozen evolutionary accidents. Experimental results available for natural RNA populations are in qualitative agreement with our observations. 1) S.C. Manrubia, C. Briones, RNA 13 (2007), 97-107.\\ 2) M. Stich, C. Briones, S.C. Manrubia, BMC Evol. Biol., submitted.

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