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Originally published as Genetics Published Articles Ahead of Print on September 14, 2008.
Genetics, Vol. 180, 1501-1509, November 2008, Copyright © 2008
doi:10.1534/genetics.107.082610
Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution
Rick Durrett*,1 and
Deena Schmidt
* Department of Mathematics and Center for Applied Mathematics, Cornell University, Ithaca, New York 14853
1 Corresponding author: 523 Malott Hall, Department of Mathematics, Cornell University, Ithaca, NY 14853.
E-mail: rtd1{at}cornell.edu
Results of Nowak and collaborators concerning the onset of cancer due to the inactivation of tumor suppressor genes give the distribution of the time until some individual in a population has experienced two prespecified mutations and the time until this mutant phenotype becomes fixed in the population. In this article we apply these results to obtain insights into regulatory sequence evolution in Drosophila and humans. In particular, we examine the waiting time for a pair of mutations, the first of which inactivates an existing transcription factor binding site and the second of which creates a new one. Consistent with recent experimental observations for Drosophila, we find that a few million years is sufficient, but for humans with a much smaller effective population size, this type of change would take >100 million years. In addition, we use these results to expose flaws in some of Michael Behe's arguments concerning mathematical limits to Darwinian evolution.
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Genetics 2008 180: NP.
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  M. J. Behe Waiting Longer for Two Mutations Genetics, February 1, 2009; 181(2): 819 - 820. [Full Text] [PDF]
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R. Durrett and D. Schmidt Reply to Michael Behe Genetics, February 1, 2009; 181(2): 821 - 822. [Full Text] [PDF]
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