Polymer physics of structural evolution in synthetic yeast chromosomes

Polymer physics of structural evolution in synthetic yeast chromosomes
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合成酵母染色体结构进化的高分子物理学

DOI:
10.1101/2022.09.14.507906
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发表时间:
2022
期刊:
--
影响因子:
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通讯作者:
Stracquadanio G
Stracquadanio G
中科院分区:
--
文献类型:
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作者:
Stracquadanio G

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酵母SCRaMbLE是使用设计的合成酵母染色体通过基因组重排产生组合多样性的实验方法。这些事件通过Cre重组酶的活性发生在设计的loxPsym重组位点处。虽然合成SCRaMbLE系统的目的是探索最小的基因组,并允许快速的基因组进化,重组的模式也反映了固有的性质,DNA循环所需的聚结对loxPsym sites.Genomes的SCRaMbLE产生的酵母菌株进行了分析,在这里使用一个新的统计力学模型,称为SCRaMbLE聚合物相互作用(SPI)模型。SPI使用聚合物物理模型的重组,并实现有效的拒绝采样和直方图重新加权算法进行SCRaMbLE实验silico.Using SPI,我们发现,实验观察到的重组事件是一致的随机游走标度指数范围在0.45和0.6之间,跨越值为0.55的高斯聚合物和0.588的自避免行走。SPI为研究SCRaMbLE重组和大规模并行基因组重组实验提供了一个高度精确的工具。
Yeast SCRaMbLE is an experimental method using designed synthetic yeast chromosomes to generate combinatorial diversity through genome rearrangements. These events occur at designed loxPsym recombination sites through the activity of Cre recombinase. While the synthetic SCRaMbLE system was designed to explore minimal genomes and permit rapid genome evolution, the pattern of recombinations also reflects inherent properties of DNA looping required to coalesce pairs of loxPsym sites.Genomes of yeast strains generated by SCRaMbLE are analyzed here using a new statistical mechanics model, called the SCRaMbLE Polymer Interaction (SPI) model. SPI uses polymer physics to model recombinations, and implements efficient rejection sampling and histogram reweighting algorithms to conduct SCRaMbLE experimentsin silico.Using SPI, we found that recombination events observed experimentally are consistent with a random walk scaling exponent ranging between 0.45 and 0.6, which spans values of 0.55 for a Gaussian polymer and 0.588 for a self-avoiding walk. SPI provides a highly accurate tool to study SCRaMbLE recombinations and massively parallel genome recombination experiments.
DOI: 10.1002/bip.1974.360130115
发表时间: 1974-01-01
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影响因子: 2.9
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