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合成基因组揭示了同义重编码的影响

Akos Nyerges¹, Anush Chiappino-Pepe¹, Bogdan Budnik²

¹Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

bioRxiv : the preprint server for biology

|June 25, 2024

概括

科学家们使用更少的编码器设计了一种合成大肠杆菌 (Escherichia coli) 基因组,克服了遗传代码变化的致死性. 这项工作使得更安全的转基因生物和新型生物聚合物生产成为可能.

科学领域:

合成生物学合成生物学
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

工程生物的遗传密码使病毒耐药性,修饰基因的制,以及非自然聚合物的生产成为可能.
对这些目标来说,重新分配子至关重要,但往往是致命的,对身体健康的影响不太了解.

研究的目的:

为了探索同义代码子重新分配 (重新编码) 的健身后果.
开发一个工作流程,用于构建和故障排除合成基因组.
为了使有机体具有增强的遗传特性的创造.

主要方法:

采用了全基因组合成和多重化定向进化.
用基因组-转录基因组-翻译基因组-蛋白质组共同分析来分析重新编码的基因组.
为应对合成基因组挑战,开发了一种数据驱动的,基于多omics的工作流.

主要成果:

使用 57 个编码子组装了一个合成的 Escherichia coli 基因组,克服了来自 62,007 个同名编码子交换的致命性.
发现同义重编引发了转录噪声,包括反意义RNA,扰乱了转录和蛋白质组.
消除编码子揭示了神秘的促进子,这表明自然编码子的使用可以最大限度地减少转录噪声.

结论:

同义代码子选择显著影响生物体的健康和基因组稳定性.
开发的工作流成功地解决了合成基因组构造的故障.
这项研究为具有遗传防火墙和扩展生物合成能力的工程生物铺平了道路.

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