Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution
Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution
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DOI：
10.1534/genetics.107.082610
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发表时间：
2008-11-01
期刊：
影响因子：
3.3
通讯作者：
Schmidtt, Deena
中科院分区：
文献类型：
--
作者：
Durrett, Rick;Schmidtt, Deena
Nowak及其合作者关于肿瘤抑制基因失活导致癌症发病的研究结果给出了一个群体中某个个体经历两个预先指定的突变的时间分布，以及该突变表型在群体中固定的时间分布。在这篇文章中，我们应用这些结果，以获得在果蝇和人类的调控序列进化的见解。特别是，我们研究了一对突变的等待时间，第一个突变使现有的转录因子结合位点失活，第二个突变产生一个新的突变。与最近对果蝇的实验观察相一致，我们发现几百万年就足够了，但对于有效种群规模小得多的人类来说，这种类型的变化需要> 1亿年，此外，我们使用这些结果来揭露迈克尔·贝赫关于达尔文进化论数学极限的一些论点中的缺陷。
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.