title: Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding.
abstract: BACKGROUND
  The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. However, in a number of recent studies, a prevalence of antagonistic epistasis (the tendency of multiple mutations to have a mitigating rather than reinforcing effect) has been observed.
  
  
  RESULTS
  We studied in silico the net amount and form of epistatic interactions in RNA secondary structure folding by measuring the fraction of neutral mutants as a function of mutational distance d. We found a clear prevalence of antagonistic epistasis in RNA secondary structure folding. By relating the fraction of neutral mutants at distance d to the average neutrality at distance d, we showed that this prevalence derives from the existence of many compensatory mutations at larger mutational distances.
  
  
  CONCLUSIONS
  Our findings imply that the average direction of epistasis in simple fitness landscapes is directly related to the density with which fitness peaks are distributed in these landscapes.
authors.affiliation: Digital Life Laboratory 136-93, California Institute of Technology, Pasadena, CA 91125, USA. wilke@caltech.edu
authors.forename: Claus O
authors.initials: CO
authors.lastname: Wilke
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lenski
authors.forename: Christoph
authors.initials: C
authors.lastname: Adami
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D014644:Genetic Variation; D016678:Genome; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D008962:Models, Theoretical; D016296:Mutagenesis; D009154:Mutation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D012984:Software
chemical_list: D012313:RNA