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天津大学合成生物学元英进教授团队首次实现对人造环形染色体的基因组重排

发布: 2018-09-19 9,330阅读 362评论

2018年9月17日，在最新一期上线的国际学术期刊《自然·通讯》上刊载了一篇名为《环形5号染色体基因组重排》的论文。文章公布了天津大学元英进教授团队首次将自主设计合成的5号酿酒酵母环状染色体进行基因组重排的相关研究成果，为探索环形染色体结构变异和功能提供了新的研究思路和模型。

染色体结构变异对生物性状多样性具有重要影响。我们常见的真核生物染色体一般都是成线性的棒状结构，而人类的某些染色体发生变异后会出现“成环”的现象。染色体的环化与癌症、癫痫、智力发育迟缓、白血病等多种疾病的发生密切相关。目前对环形染色体结构变异及所产生表型的认知相对匮乏。元英进教授团队以此前人工合成的酿酒酵母环形5号染色体为研究对象，利用SCRaMbLE基因组重排系统对其进行基因组重排，发现环形染色体不同于线性染色体的多种结构性变化。

图1.环形V号染色体重排产生基因型和表型多样性

研究人员选择了抗癌活性化合物——紫色杆菌素前体物（PDV）作为目标性状，通过多轮基因组重排来探究染色体结构变异对细胞功能的影响。研究发现，环形染色体基因组重排过程中会连续产生复杂的基因组结构变异和表型优化。环形染色体的重排后，发现了1、3、6、12、13和环形5号染色体的数目加倍，形成染色体非整倍体酵母菌株。重排使染色体自身产生更多的非对称性结构变异，包括DNA片段的重复和片段插入；经过5次连续诱导重排后，所获得环形染色体的长度比原始染色体增加了一倍以上。

图2.紫色杆菌素前体物产量连续提升和结构变异连续发生

环形染色体重排过程检测到更多的非天然新型结构变异。环形5号染色体在经过第一轮诱导重排后检测到29种非天然存在的新型结构变异，在两轮连续诱导重排后增加到47个；多轮实验后共计检测到53种新型结构变异。将第一轮重排染色体中检测到的29个结构变异分别导入细胞中，在其中11种当中筛选得到了PDV合成产量提升的菌株。同时发现，未表征基因YER182W的缺失与PDV的产量提升具有相关性。

研究表明，环形染色体在基因组重排过程中通过修改染色体数目和结构可以持续产生染色体结构变异和细胞表型增强，进而推动基因组的进化，为理解DNA基因型与生物表型关系提供了有效的研究模型。

图3.重排环形V号染色体内部相互关联

相关研究成果于9月17日在线发表于《自然-通讯》杂志（Nature Communications (2018). https://www.nature.com/articles/s41467-018-06216-y）。天津大学化工学院的硕士研究生王娟和谢泽雄副教授为该文章的共同第一作者，元英进教授为通讯作者。该研究获得了国家自然科学基金（21621004、21750001）和国家重点基础研究发展计划（“973”计划：2014CB745100）等基金的大力支持。

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