Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Department of Biochemistry, University of Cambridge, Cambridge, UK.
Science. 2022 Nov 4;378(6619):516-523. doi: 10.1126/science.add8943. Epub 2022 Oct 20.
The near-universal genetic code defines the correspondence between codons in genes and amino acids in proteins. We refactored the structure of the genetic code in and created orthogonal genetic codes that restrict the escape of synthetic genetic information into natural life. We developed orthogonal and mutually orthogonal horizontal gene transfer systems, which permit the transfer of genetic information between organisms that use the same genetic code but restrict the transfer of genetic information between organisms that use different genetic codes. Moreover, we showed that locking refactored codes into synthetic organisms completely blocks invasion by mobile genetic elements, including viruses, which carry their own translation factors and successfully invade organisms with canonical and compressed genetic codes.
近乎通用的遗传密码定义了基因中的密码子与蛋白质中的氨基酸之间的对应关系。我们重构了遗传密码的结构,并创建了正交遗传密码,限制了合成遗传信息逃逸到自然生命中。我们开发了正交和相互正交的水平基因转移系统,允许在使用相同遗传密码的生物体之间转移遗传信息,但限制了在使用不同遗传密码的生物体之间转移遗传信息。此外,我们还表明,将重构的密码锁定在合成生物体中完全阻止了移动遗传元件的入侵,包括携带自身翻译因子并成功入侵具有规范和压缩遗传密码的生物体的病毒。