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Genetics. Dec 2001; 159(4): 1393–1404.
PMCID: PMC1461900

Profiles of adaptation in two similar viruses.


The related bacteriophages phiX174 and G4 were adapted to the inhibitory temperature of 44 degrees and monitored for nucleotide changes throughout the genome. Phage were evolved by serial transfer at low multiplicity of infection on rapidly dividing bacteria to select genotypes with the fastest rates of reproduction. Both phage showed overall greater fitness effects per substitution during the early stages of adaptation. The fitness of phiX174 improved from -0.7 to 5.6 doublings of phage concentration per generation. Five missense mutations were observed. The earliest two mutations accounted for 85% of the ultimate fitness gain. In contrast, G4 required adaptation to the intermediate temperature of 41.5 degrees before it could be maintained at 44 degrees. Its fitness at 44 degrees increased from -2.7 to 3.2, nearly the same net gain as in phiX174, but with three times the opportunity for adaptation. Seventeen mutations were observed in G4: 14 missense, 2 silent, and 1 intergenic. The first 3 missense substitutions accounted for over half the ultimate fitness increase. Although the expected pattern of periodic selective sweeps was the most common one for both phage, some mutations were lost after becoming frequent, and long-term polymorphism was observed. This study provides the greatest detail yet in combining fitness profiles with the underlying pattern of genetic changes, and the results support recent theories on the range of fitness effects of substitutions fixed during adaptation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bennett AF, Dao KM, Lenski RE. Rapid evolution in response to high-temperature selection. Nature. 1990 Jul 5;346(6279):79–81. [PubMed]
  • Begun DJ, Whitley P. Genetics of alpha-amanitin resistance in a natural population of Drosophila melanogaster. Heredity (Edinb) 2000 Aug;85(Pt 2):184–190. [PubMed]
  • Bull JJ, Badgett MR, Wichman HA, Huelsenbeck JP, Hillis DM, Gulati A, Ho C, Molineux IJ. Exceptional convergent evolution in a virus. Genetics. 1997 Dec;147(4):1497–1507. [PMC free article] [PubMed]
  • Bull JJ, Badgett MR, Wichman HA. Big-benefit mutations in a bacteriophage inhibited with heat. Mol Biol Evol. 2000 Jun;17(6):942–950. [PubMed]
  • Buonagurio DA, Nakada S, Parvin JD, Krystal M, Palese P, Fitch WM. Evolution of human influenza A viruses over 50 years: rapid, uniform rate of change in NS gene. Science. 1986 May 23;232(4753):980–982. [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]
  • Bush RM, Bender CA, Subbarao K, Cox NJ, Fitch WM. Predicting the evolution of human influenza A. Science. 1999 Dec 3;286(5446):1921–1925. [PubMed]
  • Dowell CE. Growth of bacteriophage phiX-174 at elevated temperatures. J Gen Virol. 1980 Jul;49(1):41–50. [PubMed]
  • Elena SF, Cooper VS, Lenski RE. Punctuated evolution caused by selection of rare beneficial mutations. Science. 1996 Jun 21;272(5269):1802–1804. [PubMed]
  • Escarmís C, Dávila M, Domingo E. Multiple molecular pathways for fitness recovery of an RNA virus debilitated by operation of Muller's ratchet. J Mol Biol. 1999 Jan 15;285(2):495–505. [PubMed]
  • Gerrish PJ, Lenski RE. The fate of competing beneficial mutations in an asexual population. Genetica. 1998;102-103(1-6):127–144. [PubMed]
  • Godson GN, Barrell BG, Staden R, Fiddes JC. Nucleotide sequence of bacteriophage G4 DNA. Nature. 1978 Nov 16;276(5685):236–247. [PubMed]
  • Golding GB, Dean AM. The structural basis of molecular adaptation. Mol Biol Evol. 1998 Apr;15(4):355–369. [PubMed]
  • Helling RB, Vargas CN, Adams J. Evolution of Escherichia coli during growth in a constant environment. Genetics. 1987 Jul;116(3):349–358. [PMC free article] [PubMed]
  • Hill WG, Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966 Dec;8(3):269–294. [PubMed]
  • Adams J, Puskas-Rozsa S, Simlar J, Wilke CM. Adaptation and major chromosomal changes in populations of Saccharomyces cerevisiae. Curr Genet. 1992 Jul;22(1):13–19. [PubMed]
  • Lenski RE. Bacterial evolution and the cost of antibiotic resistance. Int Microbiol. 1998 Dec;1(4):265–270. [PubMed]
  • Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, Hutchison CA, Slocombe PM, Smith M. Nucleotide sequence of bacteriophage phi X174 DNA. Nature. 1977 Feb 24;265(5596):687–695. [PubMed]
  • Schrag SJ, Perrot V. Reducing antibiotic resistance. Nature. 1996 May 9;381(6578):120–121. [PubMed]
  • Mitsuhashi S. Drug resistance in bacteria: history, genetics and biochemistry. J Int Med Res. 1993 Jan-Feb;21(1):1–14. [PubMed]
  • TESSMAN ES, TESSMAN I. Genetic recombination in phage S13. Virology. 1959 Apr;7(4):465–467. [PubMed]
  • Turner PE, Chao L. Prisoner's dilemma in an RNA virus. Nature. 1999 Apr 1;398(6726):441–443. [PubMed]
  • Orr HA. Adaptation and the cost of complexity. Evolution. 2000 Feb;54(1):13–20. [PubMed]
  • Papadopoulos D, Schneider D, Meier-Eiss J, Arber W, Lenski RE, Blot M. Genomic evolution during a 10,000-generation experiment with bacteria. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3807–3812. [PMC free article] [PubMed]
  • Wichman HA, Badgett MR, Scott LA, Boulianne CM, Bull JJ. Different trajectories of parallel evolution during viral adaptation. Science. 1999 Jul 16;285(5426):422–424. [PubMed]
  • Riehle MM, Bennett AF, Long AD. Genetic architecture of thermal adaptation in Escherichia coli. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):525–530. [PMC free article] [PubMed]

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