美国哥伦比亚大学Harris H. Wang团队在研究中取得进展。他们发现人工合成序列可增加细胞内遗传信息的稳定性和约束性。2019年8月9日出版的《科学》发表了这项成果。

研究人员提出了一种通用策略，其通过重叠基因的计算设计来保护和约束遗传信息。将一段序列与一个必需基因进行重叠会改变其适应性情况并产生一个受限的进化路径，即使对于同义突变也是如此。在目的基因中嵌入毒素基因可限制其横向传播。研究人员进一步展示了一种多重和可扩展的方法，其通过构建和测试超过7500个重叠序列的设计在天然同源物中产生有功能但极为不同的变体。这项工作可以对自然和工程的重叠基因进行更深入的探索，并促进新兴应用中遗传稳定性和生物防护的增强。

据悉，在合成生物学中，稳定基因改造功能和限制重组DNA于目标宿主内的方法，对于应对自然突变积累和普遍的横向基因流是必需的。

附：英文原文

Title: Synthetic sequence entanglement augments stability and containment of genetic information in cells

Author: Tomasz Blazejewski, Hsing-I Ho, Harris H. Wang

Issue&Volume: Vol. 365, Issue 6453, pp. 595-598

Abstract: In synthetic biology, methods for stabilizing genetically engineered functions and confining recombinant DNA to intended hosts are necessary to cope with natural mutation accumulation and pervasive lateral gene flow. We present a generalizable strategy to preserve and constrain genetic information through the computational design of overlapping genes. Overlapping a sequence with an essential gene altered its fitness landscape and produced a constrained evolutionary path, even for synonymous mutations. Embedding a toxin gene in a gene of interest restricted its horizontal propagation. We further demonstrated a multiplex and scalable approach to build and test >7500 overlapping sequence designs, yielding functional yet highly divergent variants from natural homologs. This work enables deeper exploration of natural and engineered overlapping genes and facilitates enhanced genetic stability and biocontainment in emerging applications.

DOI: 10.1126/science.aav5477

Source:https://science.sciencemag.org/content/365/6453/595