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一个染色体段的合成对线化使得远距离的属之间不相容的基因剖析成为可能

Shawn H Yang¹, Alessandro L V Coradini^1,2, Cara B Hull¹

¹Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.

bioRxiv : the preprint server for biology

|November 19, 2025

概括

线性化合成染色体来研究不同的生物体. 这种方法创造了一种混合酵母基因组,揭示了遗传不相容性,并使得无法自然繁殖的物种之间的特征分析成为可能.

科学领域:

合成生物学合成生物学
基因组学就是基因组学.
酵母遗传学酵母遗传学

背景情况:

由于生殖障碍和基因组差异,不同生物之间的遗传分析具有挑战性.
线性化提供了一种方法来克服这些挑战,通过合成具有本地基因内容和组织的染色体.

研究的目的:

为了研究是否可以对与远距离相关的酵母物种,Kluyveromyces marxianus和Saccharomyces cerevisiae应用线性化.
评估创建模拟基因组和分析遗传不相容性的可行性.

主要方法:

应用了对线化,在S. cerevisiae染色体内合成了一个~35kb的K. marxianusDNA段.
利用AlphaFold来预测蛋白质与蛋白质的相互作用,并确定生长成本的来源.
补充了正义蛋白质,并替换了不兼容的基因以缓解生长缺陷.

主要成果:

一个来自K. marxianus的合成染色体段成功地集成到S. cerevisiae中.
由于不兼容的K. marxianus蛋白质,观察到显著的生长成本.
计算预测和基因改造成功地减轻了增长成本.

结论:

线性化是创建模拟基因组的可行工具,用于研究不同生物体之间的遗传不相容性.
被破坏的蛋白质-蛋白质相互作用是遗传不相容性的主要来源,可预测 in silico.
在S. cerevisiae和K. marxianus.之间可能存在数百种遗传不兼容性.

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