Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution Export

@article{citeulike:3279412, abstract = {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. 10.1534/genetics.107.082610}, address = {Cornell University.}, author = {Durrett, Rick and Schmidt, Deena}, citeulike-article-id = {3279412}, citeulike-linkout-0 = {http://dx.doi.org/10.1534/genetics.107.082610}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18791261}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18791261}, day = {1}, doi = {10.1534/genetics.107.082610}, issn = {0016-6731}, journal = {Genetics}, keywords = {cancer, evodynamics, evolution}, month = {November}, number = {3}, pages = {1501--1509}, posted-at = {2009-03-10 19:24:33}, priority = {2}, title = {Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution}, url = {http://dx.doi.org/10.1534/genetics.107.082610}, volume = {180}, year = {2008} }

TY - JOUR ID - citeulike:3279412 L3 - citeulike-article-id:3279412 N2 - 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. 10.1534/genetics.107.082610 IS - 3 JF - Genetics SN - 0016-6731 AD - Cornell University. EP - 1509 TI - Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution VL - 180 SP - 1501 KW - cancer KW - evodynamics KW - evolution AU - Durrett, Rick AU - Schmidt, Deena PY - 2008/11/01/ UR - http://dx.doi.org/10.1534/genetics.107.082610 ER -