Self-dependence of the Mutation Rate

目标是确定生物体基因组中可遗传突变的发生速度是否取决于已经存在的突变的数量。以前已经证明，突变累积了200代的不同线虫种群在繁殖率(“适合度”)方面经历了不同的下降速度。这个过程将在这些具有高适应度和低适应度的股票的子集上再重复135代。如果突变率取决于当前的突变状态，那么低适合度股票的下降速度会比高适合度股票的下降速度更快。一个复杂的问题是，突变对适应度的影响可能取决于已经存在的突变的数量，因此突变的累积影响并不等于单个影响的总和。为了区分这两种可能性，将对代表性种群的基因组进行测序，直接建立当前突变状态和未来突变率之间的关系。突变率通常被认为是物种的固定属性，但如果突变率取决于已经存在的突变的数量，就会对保护生物学、农业和医学产生重要的后果。例如，即使在污染物从环境中移除后，环境中突变污染物水平的暂时增加也可能对突变率产生持久的影响。了解当前和未来突变状态之间的关系，将能够在短期内预测增加突变负荷的环境因素的未来后果。

The goal is to determine whether the rate at which heritable mutations occur in an organism's genome depends on the number of mutations that are already present. It was previously demonstrated that different stocks of nematodes in which mutations accumulated for 200 generations experienced different rates of decline in reproductive rate ("fitness"). The process will be repeated for a further 135 generations on a subset of these stocks with high and low fitness. If the mutation rate depends on the current mutational status, low fitness stocks will decline more rapidly than high fitness stocks. A complication is that the effect of a mutation on fitness may depend on the number of mutations already present, whereby the cumulative effects of mutations do not equal the sum of the individual effects. To distinguish between the two possibilities, the genomes of representative stocks will be sequenced, directly establishing the relationship between current mutational status and future mutation rate. The mutation rate is usually considered a fixed property of a species, but if the mutation rate depends on the number of mutations already present, there are important consequences for conservation biology, agriculture, and medicine. For example, a temporary increase in the level of a mutagenic pollutant in the environment could have lasting effects on the mutation rate even after the pollutant was removed from the environment. Understanding the relationship between current and future mutational status will enable prediction of the future consequences of environmental factors that increase the mutation load in the short term.