新突变的适应度效应决定了进化过程的关键特性。有益突变推动进化，但选择也受到小效应有害突变频率的影响，其综合效应可能会给原本具有适应性的谱系带来负担，并改变病毒、微生物和肿瘤等克隆进化生物体的进化轨迹和结果。这些重要突变的影响较小，因此很难准确测量其发生率。在微生物中，评估突变对生长的影响尤其具有指导意义，因为这种复杂的表型与克隆进化生物体的适应性密切相关。在这里，我们对来自突变积累菌株的细胞进行高通量延时显微镜检查，以精确推断突变对芽殖酵母（酿酒酵母）生长速率的影响分布。我们表明，突变对生长率的影响绝大多数是负面的，高度偏向于非常小的影响大小，而且频率足以表明有害的搭便车者可能会给进化的谱系带来重大负担。通过使用在野生型或滑移修复缺陷背景中积累突变的品系，我们进一步阐明了两种常见突变类型（单核苷酸替换和简单序列重复插入缺失）的影响，并表明它们对酵母生长具有独特的影响速度。尽管简单序列重复突变的平均影响非常小（约 0.3%），但许多突变确实会改变生长速率，这意味着此类频繁突变具有重要的进化影响。版权所有：© 2024 Plavskin 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

The fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult. In microbes, assessing the effect of mutations on growth can be especially instructive, as this complex phenotype is closely linked to fitness in clonally evolving organisms. Here, we perform high-throughput time-lapse microscopy on cells from mutation-accumulation strains to precisely infer the distribution of mutational effects on growth rate in the budding yeast, Saccharomyces cerevisiae. We show that mutational effects on growth rate are overwhelmingly negative, highly skewed towards very small effect sizes, and frequent enough to suggest that deleterious hitchhikers may impose a significant burden on evolving lineages. By using lines that accumulated mutations in either wild-type or slippage repair-defective backgrounds, we further disentangle the effects of 2 common types of mutations, single-nucleotide substitutions and simple sequence repeat indels, and show that they have distinct effects on yeast growth rate. Although the average effect of a simple sequence repeat mutation is very small (approximately 0.3%), many do alter growth rate, implying that this class of frequent mutations has an important evolutionary impact.Copyright: © 2024 Plavskin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.