• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Jun 2004; 167(2): 559–567.
PMCID: PMC1470902

Epistasis and its relationship to canalization in the RNA virus phi 6.


Although deleterious mutations are believed to play a critical role in evolution, assessing their realized effect has been difficult. A key parameter governing the effect of deleterious mutations is the nature of epistasis, the interaction between the mutations. RNA viruses should provide one of the best systems for investigating the nature of epistasis because the high mutation rate allows a thorough investigation of mutational effects and interactions. Nonetheless, previous investigations of RNA viruses by S. Crotty and co-workers and by S. F. Elena have been unable to detect a significant effect of epistasis. Here we provide evidence that positive epistasis is characteristic of deleterious mutations in the RNA bacteriophage phi 6. We estimated the effects of deleterious mutations by performing mutation-accumulation experiments on five viral genotypes of decreasing fitness. We inferred positive epistasis because viral genotypes with low fitness were found to be less sensitive to deleterious mutations. We further examined environmental sensitivity in these genotypes and found that low-fitness genotypes were also less sensitive to environmental perturbations. Our results suggest that even random mutations impact the degree of canalization, the buffering of a phenotype against genetic and environmental perturbations. In addition, our results suggest that genetic and environmental canalization have the same developmental basis and finally that an understanding of the nature of epistasis may first require an understanding of the nature of canalization.

Full Text

The Full Text of this article is available as a PDF (109K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ancel LW, Fontana W. Plasticity, evolvability, and modularity in RNA. J Exp Zool. 2000 Oct 15;288(3):242–283. [PubMed]
  • Barton NH, Charlesworth B. Why sex and recombination? Science. 1998 Sep 25;281(5385):1986–1990. [PubMed]
  • Bergman Aviv, Siegal Mark L. Evolutionary capacitance as a general feature of complex gene networks. Nature. 2003 Jul 31;424(6948):549–552. [PubMed]
  • Burch CL, Chao L. Evolution by small steps and rugged landscapes in the RNA virus phi6. Genetics. 1999 Mar;151(3):921–927. [PMC free article] [PubMed]
  • Chao L. Evolution of sex in RNA viruses. J Theor Biol. 1988 Jul 8;133(1):99–112. [PubMed]
  • Chao L. Fitness of RNA virus decreased by Muller's ratchet. Nature. 1990 Nov 29;348(6300):454–455. [PubMed]
  • Chao L, Tran TT, Tran TT. The advantage of sex in the RNA virus phi6. Genetics. 1997 Nov;147(3):953–959. [PMC free article] [PubMed]
  • Chao Lin, Rang Camilla U, Wong Linda E. Distribution of spontaneous mutants and inferences about the replication mode of the RNA bacteriophage phi6. J Virol. 2002 Apr;76(7):3276–3281. [PMC free article] [PubMed]
  • Charlesworth B. The effect of synergistic epistasis on the inbreeding load. Genet Res. 1998 Feb;71(1):85–89. [PubMed]
  • Crotty S, Cameron CE, Andino R. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6895–6900. [PMC free article] [PubMed]
  • de Visser JA, Hoekstra RF, van den Ende H. An experimental test for synergistic epistasis and its application in Chlamydomonas. Genetics. 1997 Mar;145(3):815–819. [PMC free article] [PubMed]
  • DUN RB, FRASER AS. Selection for an invariant character; vibrissa number in the house mouse. Nature. 1958 Apr 5;181(4614):1018–1019. [PubMed]
  • Elena SF. Little evidence for synergism among deleterious mutations in a nonsegmented RNA virus. J Mol Evol. 1999 Nov;49(5):703–707. [PubMed]
  • Elena SF, Lenski RE. Test of synergistic interactions among deleterious mutations in bacteria. Nature. 1997 Nov 27;390(6658):395–398. [PubMed]
  • Gibson G, Wagner G. Canalization in evolutionary genetics: a stabilizing theory? Bioessays. 2000 Apr;22(4):372–380. [PubMed]
  • Keightley PD, Ohnishi O. EMS-induced polygenic mutation rates for nine quantitative characters in Drosophila melanogaster. Genetics. 1998 Feb;148(2):753–766. [PMC free article] [PubMed]
  • Seager RD, Ayala FJ. Chromosome interactions in Drosophila melanogaster. I. Viability studies. Genetics. 1982 Nov;102(3):467–483. [PMC free article] [PubMed]
  • Kibota TT, Lynch M. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996 Jun 20;381(6584):694–696. [PubMed]
  • Seager RD, Ayala FJ, Marks RW. Chromosome interactions in Drosophila melanogaster. II. Total fitness. Genetics. 1982 Nov;102(3):485–502. [PMC free article] [PubMed]
  • Kondrashov AS. Selection against harmful mutations in large sexual and asexual populations. Genet Res. 1982 Dec;40(3):325–332. [PubMed]
  • Kondrashov AS. Muller's ratchet under epistatic selection. Genetics. 1994 Apr;136(4):1469–1473. [PMC free article] [PubMed]
  • Kondrashov AS, Crow JF. Haploidy or diploidy: which is better? Nature. 1991 May 23;351(6324):314–315. [PubMed]
  • TEBB G, THODAY JM. Stability in development and relational balance of X-chromosomes in Drosophila melanogaster. Nature. 1954 Dec 11;174(4441):1109–1110. [PubMed]
  • Vidaver AK, Koski RK, Van Etten JL. Bacteriophage phi6: a Lipid-Containing Virus of Pseudomonas phaseolicola. J Virol. 1973 May;11(5):799–805. [PMC free article] [PubMed]
  • Lenski RE, Ofria C, Collier TC, Adami C. Genome complexity, robustness and genetic interactions in digital organisms. Nature. 1999 Aug 12;400(6745):661–664. [PubMed]
  • Mindich L, Sinclair JF, Levine D, Cohen J. Genetic studies of temperature-sensitive and nonsense mutants of bacteriophage phi6. Virology. 1976 Nov;75(1):218–223. [PubMed]
  • Wagner A, Wagner GP, Similion P. Epistasis can facilitate the evolution of reproductive isolation by peak shifts: a two-locus two-allele model. Genetics. 1994 Oct;138(2):533–545. [PMC free article] [PubMed]
  • Mukai T. The Genetic Structure of Natural Populations of DROSOPHILA MELANOGASTER. VII Synergistic Interaction of Spontaneous Mutant Polygenes Controlling Viability. Genetics. 1969 Mar;61(3):749–761. [PMC free article] [PubMed]
  • Whitlock MC, Bourguet D. Factors affecting the genetic load in Drosophila: synergistic epistasis and correlations among fitness components. Evolution. 2000 Oct;54(5):1654–1660. [PubMed]
  • Peters AD, Keightley PD. A test for epistasis among induced mutations in Caenorhabditis elegans. Genetics. 2000 Dec;156(4):1635–1647. [PMC free article] [PubMed]
  • Zeyl C, DeVisser JA. Estimates of the rate and distribution of fitness effects of spontaneous mutation in Saccharomyces cerevisiae. Genetics. 2001 Jan;157(1):53–61. [PMC free article] [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...