Populations of microbes are constantly evolving heterogeneity that selection acts upon, yet heterogeneity is nontrivial to assess methodologically. The necessary practice of isolating single-cell colonies and thus subclone lineages for establishing, transferring, and using a strain results in single-cell bottlenecks with a generally neglected effect on the characteristics of the strain itself. Here, we present evidence that various subclone lineages for industrial yeasts sequenced for recent genomic studies show considerable differences, ranging from loss of heterozygosity to aneuploidies. Subsequently, we assessed whether phenotypic heterogeneity is also observable in industrial yeast, by individually testing subclone lineages obtained from products. Phenotyping of industrial yeast samples and their newly isolated subclones showed that single-cell bottlenecks during isolation can indeed considerably influence the observable phenotype. Next, we decoupled fitness distributions on the level of individual cells from clonal interference by plating single-cell colonies and quantifying colony area distributions. We describe and apply an approach using statistical modeling to compare the heterogeneity in phenotypes across samples and subclone lineages. One strain was further used to show how individual subclonal lineages are remarkably different not just in phenotype but also in the level of heterogeneity in phenotype. With these observations, we call attention to the fact that choosing an initial clonal lineage from an industrial yeast strain may vastly influence downstream performances and observations on karyotype, on phenotype, and also on heterogeneity.

中文翻译：

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如何表征应变？工业酵母菌的克隆异质性影响表型和表型异质性

微生物种群不断演化出选择作用的异质性，但从方法学上评估异质性并非易事。分离单细胞集落和亚克隆谱系以建立、转移和使用菌株的必要做法会导致单细胞瓶颈，而通常会忽略对菌株本身特性的影响。在这里，我们提供的证据表明，为最近的基因组研究测序的工业酵母的各种亚克隆谱系显示出相当大的差异，从杂合性丧失到非整倍体。随后，我们通过单独测试从产品中获得的亚克隆谱系，评估了在工业酵母中是否也可以观察到表型异质性。工业酵母样品及其新分离的亚克隆的表型分析表明，分离过程中的单细胞瓶颈确实会显着影响可观察到的表型。接下来，我们通过铺板单细胞集落和量化集落面积分布，将单个细胞水平的适应度分布与克隆干扰分离。我们描述并应用了一种使用统计建模的方法来比较样本和亚克隆谱系之间表型的异质性。一种菌株被进一步用于展示个体亚克隆谱系如何显着不同，不仅在表型上而且在表型的异质性水平上。有了这些观察，