Research Progress in the Exploring Genomic Variations Driven by Stress Factors Using the Yeast Model

doi:10.13560/j.cnki.biotech.bull.1985.2023-0723

Abstract

Abstract:

Genomic alteration is the molecular basis for the occurrence of genetic diseases and species evolution. This process is affected by the joint action of endogenous and exogenous physical and chemical factors of the cell. The genome in model organism Saccharomyces cerevisiae is small, thus it is easy for carrying out molecular genetic manipulation, and is widely used in research related to exploring the evolutionary regulation mechanism of genome variation. This article sums the typical DNA mutation detection genetic system in yeast models, including the use of reporter genes to detect DNA mutation rates and red and white/red sectoring colonies to screen chromosomal recombinants. Further the article also discussed the application of high-throughput sequencing technology in detecting spontaneous and stress factor-induced genomic alterations. Moreover, this review summarizes the research progresses in using S. cerevisiae to investigate the impacts of temperature fluctuations, oxidative stress, anti-tumor drug, heavy metal ions, radiation, and other stressors on genome stability and genetic mechanisms. Yeast cells are prone to undergo adaptive evolution under multiple stressful conditions, and specific chromosomal structural variations is an important genetic mechanism behind the adaptation. It may provide new insights for a comprehensive understanding of the impact of stressors on genome stability and the evolutionary patterns of species under different environments by combining genetic screening systems and high-throughput analysis methods in yeast to elucidate the relationship between cellular stress factors and genome variations.

Key words: environmental stress, Saccharomyces cerevisiae, DNA mutation, genomic instability, adaptive evolution

ZHU Ying-xuan, LI Ke-jing, HE Min, ZHENG Dao-qiong. Research Progress in the Exploring Genomic Variations Driven by Stress Factors Using the Yeast Model[J]. Biotechnology Bulletin, 2023, 39(11): 191-204.

Figures/Tables 6

Fig. 1 Yeast white/red sectoring colony system to screen chromosomal crossover recombinants The homologous allele ade2-1 in the diploid yeast strain is ocher mutant. One copy of the SUP4-o gene can partially suppress this ochre mutation of ade2-1, making the colonies appear pink. Chromosomal crossover events can lead to one daughter cell having two copies of the SUP4-o gene, causing the colonies to appear white; another daughter cell without the SUP4-o gene would result in red colonies

Fig. 2 LOH events induced by DNA homologous recombination in heterozygous diploid A: The interstitial LOH or gene conversion is resulted from repairing the DSB（double-strand DNA breaks）on a sister chromatid via homologous recombination. B: A 3∶1 pattern of the crossover associated with gene conversion tract（black rectangle）indicates repairing the DSB on one sister chromatid via homologous recombination. C: Chromosome breakage during the G1 phase results in DNA breaks on both sister chromosomes. A 4∶0 gene conversion district is formed at the breakpoint after this situation is repaired

Fig. 3 Mapping genomic alterations by analyzing the relative sequencing coverages of SNP sites A: Chromosomal trisomy events. B: Chromosomal monosomy events. C: An internal deletion event in chromosome. D: A terminal deletion event in chromosome. E: Internal loss of heterozygosity（LOH）caused by gene conversion events. F: Crossover induced terminal LOH. The blue and red lines or points represent homologous chromosomes or SNP sites. The relative coverage value 0, 0.5, and 1 indicate zero, one, and two copies of DNA, respectively

Fig. 4 Characteristic mutations and genetic mechanisms of yeast cells induced by different compounds A: Potassium bromate induces cells to produce ROS, which oxidizes base G to 8-oxo-G that prefers to pair with A, causing G > T. B: MMS and bleomycin treatment induces the generation of AP sites without base. DNA polymerase δ and Rev1 can recognize AP sites and prefer to insert A and C, respectively, causing G > T and T > G. The C inserted by Rev1 pairs with the G adjacent to the AP site when DNA polymerase ζ acts, this template slippage will cause one base T deletion. C: Cisplatin treatment induces C > T substitution or C deletion

Table 1 Examples of evolutionary adaptation induced by genomic alternations in yeast

表型效应 Phenotypic effect	变异类型 Variation type	遗传机理 Genetic mechanism	参考文献 References
H₂O₂耐受性提高	Ⅳ号染色体扩增	编码硫氧还蛋白过氧化物酶的TSP2基因拷贝数上升	[70]
H₂O₂耐受性提高	VII号染色体上572-734 kb区域扩增	编码过氧化氢酶T的 CTT1基因拷贝数上升	[24]
热胁迫耐受性提高	III号染色体扩增	该染色体上至少14个与耐热相关基因表达量上调	[75]
博来霉素耐受性提高	SKY1突变， XIII号染色体右臂缺失	SKY1基因编码蛋白激酶，其缺失可抑制膜转运蛋白活性，减少药物进入细胞	[16]
乙醇耐受性提高	III号染色体扩增	未知	[76]
对亚硫酸盐环境耐受性提高	VIII和XVI号染色体易位，XV和XVI号染色体易位	染色体易位引起SSU1基因表达量提高，SSU1基因编码可泵出亚硫酸盐的膜蛋白	[77]
氮限制环境耐受性提高	含有GAP1基因区域形成eccDNA	GAP1基因编码氨基酸透性酶	[73]
尿囊素利用能力提高	DAL4基因所在区域扩增	DAL4基因编码尿囊素通透酶	[78]
尿素利用能力提高	DUR3基因所在区域扩增	DUR3基因编码尿素通透酶	[78]
冻融耐受性增强	AQY2基因所在区域扩增	AQY2基因介导水分子跨膜运输通道	[79]
氟康唑耐受性增强	ERG11基因所在区域扩增	ERG11基因编码羊毛甾醇14α-去甲基化酶，可与氟康唑结合发挥耐药性作用	[80]
雷帕霉素耐受性提高	XII号染色体扩增	维持核糖体DNA拷贝数	[71]
NaCl耐受性提高	Gcn20基因所在区域缺失	未知	[74]
5-氟胞嘧啶耐受性提高	FCY2基因所在区域扩增缺失	FCY2基因编码胞嘧啶通透酶	[74]
葡萄糖限制环境耐受性提高	IV号染色体扩增	己糖转运蛋白编码基因HXT6和HXT7扩增	[81]

Fig. 5 Different environmental stressors result in differentiated and characteristic variations in genomes Various extracellular stressors can cause DNA damage, including DNA breaks, base damage, and cross-linking, thereby inducing different types of variations. Genetic screening systems and whole-genome sequencing are crucial technical methods for detecting environmental factors induced genomic alterations in yeast

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