The contribution of epistasis to the architecture of fitness in an RNA virus
Rafael Sanjuán *, Andrés Moya *, and Santiago F. Elena † , ‡
Author Affiliations
*Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de Valencia, P.O. Box 22085, 46071 Valencia, Spain; and †Instituto de Biología Molecular y Celular de Plantas, Consejo Superior de Investigaciones Científicas–Universidad Politécnica de Valencia, 46022 Valencia, Spain
Edited by Tomoko Ohta, National Institute of Genetics, Mishima, Japan (received for review June 10, 2004)
Abstract
The tendency for genetic architectures to exhibit epistasis among mutations plays a central role in the modern synthesis of evolutionary biology and in theoretical descriptions of many evolutionary processes. Nevertheless, few studies unquestionably show whether, and how, mutations typically interact. Beneficial mutations are especially difficult to identify because of their scarcity. Consequently, epistasis among pairs of this important class of mutations has, to our knowledge, never before been explored. Interactions among genome components should be of special relevance in compacted genomes such as those of RNA viruses. To tackle these issues, we first generated 47 genotypes of vesicular stomatitis virus carrying pairs of nucleotide substitution mutations whose separated and combined deleterious effects on fitness were determined. Several pairs exhibited significant interactions for fitness, including antagonistic and synergistic epistasis. Synthetic lethals represented 50% of the latter. In a second set of experiments, 15 genotypes carrying pairs of beneficial mutations were also created. In this case, all significant interactions were antagonistic. Our results show that the architecture of the fitness depends on complex interactions among genome components.
Footnotes
‡ To whom correspondence should be addressed.
E-mail:sfelena@ibmcp.upv.es.
Author contributions: R.S. performed research; R.S. and S.F.E. analyzed data; R.S., A.M., and S.F.E. wrote the paper; and A.M. and S.F.E. designed the experiments and supervised R.S.'s Ph.D. thesis.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: hpi, hours postinoculation; MARM, mAb-resistant mutant; VSV, vesicular stomatitis virus.
Copyright © 2004, The National Academy of Sciences
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