title: Topological features of rugged fitness landscapes in sequence space.
abstract: The factors that determine the tempo and mode of protein evolution continue to be a central question in molecular evolution. Traditionally, studies of protein evolution focused on the rates of amino acid substitutions. More recently, with the availability of sequence data and advanced experimental techniques, the focus of attention has shifted toward the study of evolutionary trajectories and the overall layout of protein fitness landscapes. In this review we describe the effect of epistasis on the topology of evolutionary pathways that are likely to be found in fitness landscapes and develop a simple theory to connect the number of maladapted genotypes to the topology of fitness landscapes with epistatic interactions. Finally, we review recent studies that have probed the extent of epistatic interactions and have begun to chart the fitness landscapes in protein sequence space.
authors.affiliation: Biological Sciences Collegiate Division, University of Chicago, 924 East 57th Street, Chicago, IL 60637, USA.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Kondrashov
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), 88 Dr. Aiguader, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 23 Pg. Lluís Companys, 08010 Barcelona, Spain. Electronic address: fyodor.kondrashov@crg.es.
authors.forename: Fyodor A
authors.initials: FA
authors.lastname: Kondrashov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004843:Epistasis, Genetic; D056084:Genetic Fitness; D006801:Humans