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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Hypervariable loci in the human gut virome
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Hypervariable loci in the human gut virome

机译：人肠道病毒中的高变基因座

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Genetic variation is critical in microbial immune evasion and drug resistance, but variation has rarely been studied in complex heterogeneous communities such as the human microbiome. To begin to study natural variation, we analyzed DNA viruses present in the lower gastrointestinal tract of 12 human volunteers by determining 48 billion bases of viral DNA sequence. Viral genomes mostly showed low variation, but 51 loci of ~100 bp showed extremely high variation, so that up to 96% of the viral genomes encoded unique amino acid sequences. Some hotspots of hypervariation were in genes homologous to the bacteriophage BPP-1 viral tail-fiber gene, which is known to be hypermutagenized by a unique reverse-transcriptase (RT)-based mechanism. Unexpectedly,other hypervariable loci in our data were in previously undescribed gene types, including genes encoding predicted Ig-superfamily proteins. Most of the hypervariable loci were linked to genes encoding RTs of a single dade, which we find is the most abundant clade among gut viruses but only a minor component of bacterial RT populations. Hypervariation was targeted to 5-AAY-3' asparagine codons, which allows maximal chemical diversification of the en coded amino acids while avoiding formation of stop codons. These findings document widespread targeted hypervariation in the human gut virome, identify previously undescribed types of genes targeted for hypervariation, clarify association with RT gene clades, and motivate studies of hypervariation in the full human microbiome.
机译：遗传变异对微生物的免疫逃逸和耐药性至关重要，但是在复杂的异质群落（如人类微生物组）中很少研究遗传变异。为了开始研究自然变异，我们通过确定480亿个病毒DNA序列碱基，分析了12位志愿者的下消化道中存在的DNA病毒。病毒基因组大多显示低变异，但〜100 bp的51个基因座显示出极高的变异，因此多达96％的病毒基因组编码独特的氨基酸序列。高变的一些热点位于与噬菌体BPP-1病毒尾纤维基因同源的基因中，该基因已知是通过独特的基于逆转录酶（RT）的机制进行超诱变的。出乎意料的是，我们数据中的其他高变基因座属于先前未描述的基因类型，包括编码预测的Ig超家族蛋白的基因。大多数高变基因座都与编码单个基因的RT的基因有关，我们发现这是肠道病毒中含量最高的进化枝，但细菌RT群体中只有一小部分。高变针对于5-AAY-3'天冬酰胺密码子，其允许编码氨基酸的最大化学多样化，同时避免终止密码子的形成。这些发现证明了人类肠道病毒中广泛的靶向高变，识别了先前未描述的针对高变的基因类型，阐明了与RT基因进化枝的关联，并激发了整个人类微生物组中高变的研究。

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