Experiences trigger transgenerational small RNA-based responses in C. elegans nematodes. Dedicated machinery ensures that heritable effects are reset, but how the responses segregate in the population is unknown. We show that isogenic individuals differ dramatically in the persistence of transgenerational responses. By examining lineages of more than 20,000 worms, three principles emerge: (1) The silencing each mother initiates is distributed evenly among her descendants; heritable RNAi dissipates but is uniform in every generation. (2) Differences between lineages arise because the mothers that initiate heritable responses stochastically assume different “inheritance states” that determine the progeny’s fate. (3) The likelihood that an RNAi response would continue to be inherited increases the more generations it lasts. The inheritance states are determined by HSF-1, which regulates silencing factors and, accordingly, small RNA levels. We found that, based on the parents’ inheritance state, the descendants’ developmental rate in response to stress can be predicted.

经验触发秀丽隐杆线虫的跨代基于小RNA的反应线虫。专用机制可确保重新设置遗传效应，但响应如何在群体中分离是未知的。我们表明，同基因个体在跨代反应的持续性方面存在显着差异。通过检查超过20,000种蠕虫的血统，出现了三个原理：（1）每个母亲发起的沉默在其后代之间平均分配；可遗传的RNAi消散，但每一代都是统一的。（2）世系之间的差异是因为发起遗传反应的母亲随机地承担着决定子孙命运的不同“继承状态”。（3）RNAi应答继续被继承的可能性越大，持续的世代就越多。继承状态由HSF-1确定，HSF-1调节沉默因子，因此，小RNA水平。我们发现，基于父母的继承状态，可以预测后代对压力的发育速度。