Bursts of Genomic Instability Potentiate Phenotypic and Genomic Diversification in Saccharomyces cerevisiae.
Bursts of Genomic Instability Potentiate Phenotypic and Genomic Diversification in Saccharomyces cerevisiae.
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DOI：
10.3389/fgene.2022.912851
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发表时间：
2022
影响因子：
3.7
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中科院分区：
文献类型：
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微生物细胞如何利用其表型潜力在不断变化的环境中生存是一个复杂的生物学问题，对发病机制和物种进化具有重要影响。随机表型转换是在生命树的许多物种中观察到的一种特别令人着迷的适应性方法，它通过仍然难以定义的机制将表型多样性引入种群。在这里，我们描述了对酿酒酵母致病分离株 YJM311 群体中发生的菌落形态表型转换的机制基础的研究。我们观察到 YJM311 细胞的克隆群体产生了形态发生改变的变异集落，并且通过全基因组序列分析，发现这些变异克隆拥有由从头结构基因组变异（SV）新改变的特殊核型集合。总体而言，我们的分析表明，拷贝数改变比等位基因同一性的变化更常见，提供了这种表型变异的致病基础。个体变异携带 1 到 16 个从头拷贝数变异，其中大多数是全染色体非整倍体。值得注意的是，我们发现二倍体 YJM311 基因组的固有稳定性与驯化的实验室菌株相当，表明变异克隆所携带的 SV 集合并不是由慢性染色体不稳定 (CIN) 机制产生的。相反，我们的数据表明，这些变异克隆在间断系统基因组不稳定性（PSGI）的随机和短暂发作期间同时获得了如此复杂的核型配置。令人惊讶的是，我们发现大多数这些高度改变的变异核型在长期传代实验中以完美的保真度繁殖，这表明高非整倍性负担通常有利于延长基因组完整性。总之，我们的结果表明，YJM311 中的集落形态转换是由随机过程驱动的，其中基因组稳定性和可塑性与表型异质性整体耦合。因此，该系统同时将表型和基因组变异引入细胞群体中，从而可以在此后的许多代中保持群体多样性。
How microbial cells leverage their phenotypic potential to survive in a changing environment is a complex biological problem, with important implications for pathogenesis and species evolution. Stochastic phenotype switching, a particularly fascinating adaptive approach observed in numerous species across the tree of life, introduces phenotypic diversity into a population through mechanisms which have remained difficult to define. Here we describe our investigations into the mechanistic basis of colony morphology phenotype switching which occurs in populations of a pathogenic isolate of Saccharomyces cerevisiae, YJM311. We observed that clonal populations of YJM311 cells produce variant colonies that display altered morphologies and, using whole genome sequence analysis, discovered that these variant clones harbored an exceptional collection of karyotypes newly altered by de novo structural genomic variations (SVs). Overall, our analyses indicate that copy number alterations, more often than changes in allelic identity, provide the causative basis of this phenotypic variation. Individual variants carried between 1 and 16 de novo copy number variations, most of which were whole chromosomal aneuploidies. Notably, we found that the inherent stability of the diploid YJM311 genome is comparable to that of domesticated laboratory strains, indicating that the collections of SVs harbored by variant clones did not arise by a chronic chromosomal instability (CIN) mechanism. Rather, our data indicate that these variant clones acquired such complex karyotypic configurations simultaneously, during stochastic and transient episodes of punctuated systemic genomic instability (PSGI). Surprisingly, we found that the majority of these highly altered variant karyotypes were propagated with perfect fidelity in long-term passaging experiments, demonstrating that high aneuploidy burdens can often be conducive with prolonged genomic integrity. Together, our results demonstrate that colony morphology switching in YJM311 is driven by a stochastic process in which genome stability and plasticity are integrally coupled to phenotypic heterogeneity. Consequently, this system simultaneously introduces both phenotypic and genomic variation into a population of cells, which can, in turn perpetuate population diversity for many generations thereafter.
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影响因子：
2.5
作者：
Heasley LR;Sampaio NMV;Argueso JL
通讯作者：
Argueso JL
影响因子：
11.8
作者：
Funk LC;Zasadil LM;Weaver BA
通讯作者：
Weaver BA
影响因子：
3.2
作者：
Klingberg, Trine Dano;Lesnik, Urska;Jespersen, Lene
通讯作者：
Jespersen, Lene
影响因子：
4.5
作者：
Granek JA;Magwene PM
通讯作者：
Magwene PM
影响因子：
30.8
作者：
Gao, Ruli;Davis, Alexander;McDonald, Thomas O.;Sei, Emi;Shi, Xiuqing;Wang, Yong;Tsai, Pei-Ching;Casasent, Anna;Waters, Jill;Zhang, Hong;Meric-Bernstam, Funda;Michor, Franziska;Navin, Nicholas E.
通讯作者：
Navin, Nicholas E.