title: A model of substitution trajectories in sequence space and long-term protein evolution.
abstract: The nature of factors governing the tempo and mode of protein evolution is a fundamental issue in evolutionary biology. Specifically, whether or not interactions between different sites, or epistasis, are important in directing the course of evolution became one of the central questions. Several recent reports have scrutinized patterns of long-term protein evolution claiming them to be compatible only with an epistatic fitness landscape. However, these claims have not yet been substantiated with a formal model of protein evolution. Here, we formulate a simple covarion-like model of protein evolution focusing on the rate at which the fitness impact of amino acids at a site changes with time. We then apply the model to the data on convergent and divergent protein evolution to test whether or not the incorporation of epistatic interactions is necessary to explain the data. We find that convergent evolution cannot be explained without the incorporation of epistasis and the rate at which an amino acid state switches from being acceptable at a site to being deleterious is faster than the rate of amino acid substitution. Specifically, for proteins that have persisted in modern prokaryotic organisms since the last universal common ancestor for one amino acid substitution approximately ten amino acid states switch from being accessible to being deleterious, or vice versa. Thus, molecular evolution can only be perceived in the context of rapid turnover of which amino acids are available for evolution.
authors.affiliation: Moscow Institute of Physics and Technology, Institutskiy Pereulok 9, g.Dolgoprudny, Russia Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Dinara R
authors.initials: DR
authors.lastname: Usmanova
authors.affiliation: Systématique, Adaptation et Evolution (UMR 7138), UPMC University Paris 06, CNRS, MNHN, IRD, Paris, France CIRB, Collège de France, Paris, France.
authors.forename: Luca
authors.initials: L
authors.lastname: Ferretti
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Inna S
authors.initials: IS
authors.lastname: Povolotskaya
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Vlasov
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain fyodor.kondrashov@crg.eu.
authors.forename: Fyodor A
authors.initials: FA
authors.lastname: Kondrashov
mesh_terms: D019143:Evolution, Molecular; D008957:Models, Genetic; D010802:Phylogeny; D011506:Proteins / Q000145:classification / Q000235:genetics*
chemical_list: D011506:Proteins
keywords: epistasis; fitness landscape; molecular evolution