Conventional models of genome evolution are centered around the principle that mutations form independently of each other and build up slowly over time. We characterized the occurrence of bursts of genome-wide loss-of-heterozygosity (LOH) in Saccharomyces cerevisiae, providing support for an additional nonindependent and faster mode of mutation accumulation. We initially characterized a yeast clone isolated for carrying an LOH event at a specific chromosome site, and surprisingly found that it also carried multiple unselected rearrangements elsewhere in its genome. Whole-genome analysis of over 100 additional clones selected for carrying primary LOH tracts revealed that they too contained unselected structural alterations more often than control clones obtained without any selection. We also measured the rates of coincident LOH at two different chromosomes and found that double LOH formed at rates 14- to 150-fold higher than expected if the two underlying single LOH events occurred independently of each other. These results were consistent across different strain backgrounds and in mutants incapable of entering meiosis. Our results indicate that a subset of mitotic cells within a population can experience discrete episodes of systemic genomic instability, when the entire genome becomes vulnerable and multiple chromosomal alterations can form over a narrow time window. They are reminiscent of early reports from the classic yeast genetics literature, as well as recent studies in humans, both in cancer and genomic disorder contexts. The experimental model we describe provides a system to further dissect the fundamental biological processes responsible for punctuated bursts of structural genomic variation.

常规的基因组进化模型围绕着这样的原理，即突变彼此独立形成并随着时间的推移缓慢建立。我们表征了啤酒酵母中全基因组杂合子丢失（LOH）爆发的发生，为其他非独立且更快的突变积累模式提供支持。我们最初对分离出的酵母克隆进行了表征，该克隆在特定染色体位点携带LOH事件，令人惊讶地发现它还在其基因组中的其他位置携带了多个未选择的重排。全基因组分析的另外100多个选择携带初级LOH片段的克隆显示，与未经任何选择获得的对照克隆相比，它们更经常包含未选择的结构改变。我们还测量了两个不同染色体上重合LOH的速率，发现如果两个潜在的单个LOH事件彼此独立发生，则双LOH的形成速率将比预期高14至150倍。这些结果在不同的菌株背景以及不能进入减数分裂的突变体中是一致的。我们的结果表明，当整个基因组变得脆弱并且可以在狭窄的时间窗口内形成多种染色体改变时，种群中的有丝分裂细胞子集会经历离散的系统基因组不稳定性发作。它们使人想起了经典酵母遗传学文献的早期报道，以及有关癌症和基因组疾病的人类最新研究。我们描述的实验模型提供了一个系统，可进一步剖析造成结构基因组变异的标点爆发的基本生物学过程。当整个基因组变得脆弱并且可以在狭窄的时间窗口内形成多种染色体改变时。它们使人想起了经典酵母遗传学文献的早期报道，以及有关癌症和基因组疾病的人类最新研究。我们描述的实验模型提供了一个系统，可进一步剖析造成结构基因组变异的标点爆发的基本生物学过程。当整个基因组变得脆弱并且可以在狭窄的时间窗口内形成多种染色体改变时。它们使人想起了经典酵母遗传学文献的早期报道，以及有关癌症和基因组疾病的人类最新研究。我们描述的实验模型提供了一个系统，可进一步剖析造成结构基因组变异的标点爆发的基本生物学过程。