Journal of Molecular Evolution

, Volume 41, Issue 6, pp 1160–1164 | Cite as

Why is the polymerase chain reaction resistant to in vitro evolution?

  • J. J. Bull
  • C. M. Pease


A variety of methods have been developed to amplify DNA and RNA. These methods vary in their susceptibility to evolve new molecular species differing from the starting template. PCR is exceptionally resistant to in vitro evolution, whereas methods such as Qβ replicase and 3SR are much less robust. This paper develops some simple mathematical models which suggest that PCR is resistant to in vitro evolution because the reaction controls replication in discrete cycles: fast replication is of little advantage during PCR because the reaction limits fast replicators as well as slow ones to a single copy per cycle. In contrast, continuous (isothermal) reactions, as in the Qβ replicase reaction, favor fast replicators. The advantage of fast replication is compounded in continuous reactions, because a fast replicator can complete many generations of replication during the time it takes a slow replicator to complete one generation. These models suggest that continuous amplication protocols will never achieve the robustness against in vitro evolution observed with PCR.

Key words

PCR - in vitro evolution Qβ replicase 3SR - DNA amplification 


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Copyright information

© Springer-Verlag New York Inc 1995

Authors and Affiliations

  • J. J. Bull
    • 1
  • C. M. Pease
    • 1
  1. 1.Department of ZoologyUniversity of TexasTXAustinUSA

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