Pfennig Aaron, Lomsadze Alexandre, Borodovsky Mark
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
J Mol Biol. 2023 Jul 15;435(14):168159. doi: 10.1016/j.jmb.2023.168159. Epub 2023 May 25.
Massive sequencing of microbiomes has led to the discovery of a large number of phage genomes with intermittent stop codon recoding. We have developed a computational tool, MgCod, that identifies genomic regions (blocks) with distinct stop codon recoding simultaneously with the prediction of protein-coding regions. When MgCod was used to scan a large volume of human metagenomic contigs hundreds of viral contigs with intermittent stop codon recoding were revealed. Many of these contigs originated from genomes of known crAssphages. Further analyses had shown that intermittent recoding was associated with subtle patterns in the organization of protein-coding genes, such as 'single-coding' and 'dual-coding'. The dual-coding genes, clustered into blocks, could be translated by two alternative codes producing nearly identical proteins. It was observed that the dual-coded blocks were enriched with the early-stage phage genes, while the late-stage genes were residing in the single-coded blocks. MgCod can identify types of stop codon recoding in novel genomic sequences in parallel with gene prediction. It is available for download from https://github.com/gatech-genemark/MgCod.
对微生物群落进行大规模测序已发现大量具有间歇性终止密码子重编码的噬菌体基因组。我们开发了一种计算工具MgCod，它在预测蛋白质编码区域的同时，能够识别具有独特终止密码子重编码的基因组区域（模块）。当使用MgCod扫描大量人类宏基因组重叠群时，发现了数百个具有间歇性终止密码子重编码的病毒重叠群。其中许多重叠群源自已知crAssphage的基因组。进一步分析表明，间歇性重编码与蛋白质编码基因组织中的细微模式有关，如“单编码”和“双编码”。聚集成模块的双编码基因可以通过两种替代密码子进行翻译，产生几乎相同的蛋白质。据观察，双编码模块富含早期噬菌体基因，而晚期基因则位于单编码模块中。MgCod可以在进行基因预测的同时，识别新基因组序列中的终止密码子重编码类型。可从https://github.com/gatech-genemark/MgCod下载该工具。
