Stochastic tunnels in evolutionary dynamics
Stochastic tunnels in evolutionary dynamics
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DOI：
10.1534/genetics.166.3.1571
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发表时间：
2004-03-01
期刊：
影响因子：
3.3
通讯作者：
Nowak, MA
中科院分区：
文献类型：
--
作者：
Iwasa, Y;Michor, F;Nowak, MA
我们研究了在癌症的体细胞进化中出现的一种情况。考虑到有限的复制细胞群体和一系列突变：类型0可以突变为类型1，类型1可以突变为类型2。没有反向突变。我们从类型为0的齐次总体开始。类型1的突变出现，要么灭绝，要么达到固定状态。在这两种情况下，它们都会产生2型，这种类型也可能灭绝或达到固定状态。如果突变率与种群大小的倒数相比很小，那么随机动态可以用同质种群之间的转变来描述。当总体从全0移动到全2而不是全1时，就产生了随机隧道。我们计算了当类型1与类型0相同或更小时随机隧道的精确速率。类型2的适合度最高。我们讨论了消除肿瘤抑制基因和激活遗传不稳定性的意义。虽然我们的理论是为癌症遗传学而发展的，但随机隧道是在许多情况下可能出现的普遍现象。
We study a Situation that arises in the somatic evolution of cancer. Consider a finite population of replicating cells and a sequence of mutations: type 0 can mutate to type 1, which can mutate to type 2. There is no back mutation. We start with a homogeneous population of type 0. Mutants of type 1 emerge and either become extinct or reach fixation. In both cases, they can generate type 2, which also can become extinct or reach fixation. If mutation rates are small compared to the inverse of the population size, then the stochastic dynamics can be described by transitions between homogeneous populations. A "stochastic tunnel" arises, when the population moves from all 0 to all 2 without ever being all 1. We calculate the exact rate of stochastic tunneling for the case when type 1 is as fit as type 0 or less fit. Type 2 has the highest fitness. We discuss implications for the elimination of tumor suppressor genes and the activation of genetic instability. Although our theory is developed for cancer genetics, stochastic tunnels are general phenomena that could arise in many circumstances.