A Case Study of Genomic Instability in an Industrial Strain of Saccharomyces cerevisiae.
A Case Study of Genomic Instability in an Industrial Strain of Saccharomyces cerevisiae.
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酿酒酵母工业菌株中基因组不稳定性的案例研究。
DOI：
10.1534/g3.118.200446
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发表时间：
2018-11-06
期刊：
影响因子：
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通讯作者：
Argueso JL
中科院分区：
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作者：
Rodrigues-Prause A;Sampaio NMV;Gurol TM;Aguirre GM;Sedam HNC;Chapman MJ;Malc EP;Ajith VP;Chakraborty P;Tizei PA;Pereira GAG;Mieczkowski PA;Nishant KT;Argueso JL
酿酒酵母菌株JAY 270/PE 2是一种高效的生物催化剂，用于从甘蔗原料生产生物乙醇。该菌株为异宗配合二倍体，其基因组具有同源染色体间丰富的结构多态性和核苷酸多态性。它受到许多酿酒厂青睐的原因之一是它的细胞通常不会聚集，这是一种在分批补料发酵过程中促进细胞再循环的特性。然而，长期繁殖使酵母菌群容易受到基因组不稳定性的影响，这可能引发不期望的表型如细胞聚集的出现。在JAY 270的纯培养物中，我们鉴定了反复出现的突变体，所述突变体显示母-子细胞分离缺陷，导致琼脂培养基中的粗糙菌落和液体培养中的快速沉降。我们研究了殖民地形态表型的遗传基础，发现JAY 270是ACE 2基因（ACE 2/ace 2-A7）中移码突变的杂合型，该基因编码母子细胞分离的转录调节因子。分析的所有自发粗糙集落JAY 270衍生的分离株在ACE 2所在的染色体XII区域（ace 2-A7/ace 2-A7）携带拷贝中性杂合性丢失（洛）。我们专门测量了洛率在ACE 2基因座，并在三个额外的染色体区域在JAY 270和传统的纯合二倍体实验室菌株。这种直接比较表明，两种菌株背景之间所有位点的洛率非常相似。在这个工业菌株基因组不稳定性的案例研究中，我们表明JAY 270基因组是动态的，其染色体的结构变化可能导致新的表型。然而，我们的分析还表明，相对于实验室菌株，该工业菌株的基因组不稳定性的固有水平是正常的。我们的工作提供了一个重要的参考框架，以背景化的解释工业酵母菌株的复杂基因组中观察到的不稳定过程。
The Saccharomyces cerevisiae strain JAY270/PE2 is a highly efficient biocatalyst used in the production of bioethanol from sugarcane feedstock. This strain is heterothallic and diploid, and its genome is characterized by abundant structural and nucleotide polymorphisms between homologous chromosomes. One of the reasons it is favored by many distilleries is that its cells do not normally aggregate, a trait that facilitates cell recycling during batch-fed fermentations. However, long-term propagation makes the yeast population vulnerable to the effects of genomic instability, which may trigger the appearance of undesirable phenotypes such as cellular aggregation. In pure cultures of JAY270, we identified the recurrent appearance of mutants displaying a mother-daughter cell separation defect resulting in rough colonies in agar media and fast sedimentation in liquid culture. We investigated the genetic basis of the colony morphology phenotype and found that JAY270 is heterozygous for a frameshift mutation in the ACE2 gene (ACE2/ace2-A7), which encodes a transcriptional regulator of mother-daughter cell separation. All spontaneous rough colony JAY270-derived isolates analyzed carried copy-neutral loss-of-heterozygosity (LOH) at the region of chromosome XII where ACE2 is located (ace2-A7/ace2-A7). We specifically measured LOH rates at the ACE2 locus, and at three additional chromosomal regions in JAY270 and in a conventional homozygous diploid laboratory strain. This direct comparison showed that LOH rates at all sites were quite similar between the two strain backgrounds. In this case study of genomic instability in an industrial strain, we showed that the JAY270 genome is dynamic and that structural changes to its chromosomes can lead to new phenotypes. However, our analysis also indicated that the inherent level of genomic instability in this industrial strain is normal relative to a laboratory strain. Our work provides an important frame of reference to contextualize the interpretation of instability processes observed in the complex genomes of industrial yeast strains.