Moïra B. Dion1,2, Frank Oechslin1,2 and Sylvain Moineau1,2,3
1 Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec City, G1V 0A6, Canada
1 加拿大魁北克市拉瓦尔大学科学与工程学院生物化学、微生物学和生物信息学系，G1V 0A6
2 Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval, Québec City, G1V 0A6, Canada
2 加拿大魁北克市 G1V 0A6 拉瓦尔大学牙科学院口腔生态研究小组
3 Félix d’Hérelle Reference Center for Bacterial Viruses, Université Laval, Québec City, G1V 0A6, Canada
3 Félix d’Hérelle 细菌病毒参考中心，拉瓦尔大学，加拿大魁北克市，G1V 0A6
Abstract: 摘要
Recent advances in viral metagenomics have enabled the rapid discovery of an unprecedented catalogue of phages in many biomes. While it significantly expanded our understanding of how diverse phage sequences are, it also revealed that we have only scratched the surface in the discovery of novel viruses. Yet despite their remarkable diversity at the nucleotide sequence level, the structural proteins that make up their virion particles still show strong similarities and conservation. Phages are uniquely interconnected from an evolutionary perspective and undergo multiple events of genetic exchanges in response to the selective pressure of their hosts, which fuel their diversity. In this Review, we explore phage diversity at the structural, genomic and community level as well as the complex evolutionary relationships between phages, molded by the mosaicity of their genomes.
病毒元基因组学的最新进展使我们能够在许多生物群落中快速发现前所未有的噬菌体目录。虽然这极大地扩展了我们对噬菌体序列多样性的了解，但也揭示出我们对新型病毒的发现还仅仅停留在表面。然而，尽管噬菌体在核苷酸序列水平上具有显著的多样性，但构成其病毒粒子的结构蛋白仍然显示出很强的相似性和保护性。从进化的角度看，噬菌体之间有着独特的相互联系，它们在宿主的选择性压力下经历了多次基因交换，从而促进了它们的多样性。在这篇综述中，我们将探讨噬菌体在结构、基因组和群落层面的多样性，以及噬菌体之间复杂的进化关系，这些关系是由其基因组的镶嵌性所决定的。
Phages are the most abundant and diverse biological entities on the planet. This opening statement has become a favorite of many viral ecologists. With an estimated 1031 on the planet1, phages can even outnumber bacteria by approximately ten-fold in some ecosystems. They are found in every explored biome, from the human gastrointestinal tract to the global ocean, but also in startling places such as the oceanic basement2 and a Middle Age fossilized stool specimen3. In aquatic environments, phages were shown to play major roles in biogeochemical cycling, by short-circuiting the flow of carbon through bacterial killing, known as the viral shunt1. They are also important modulators in the human gut, where they predominantly carry out a lysogenic lifestyle, which can affect their bacterial host’s physiology and metabolism4. In addition to their ubiquity, phages exhibit a plethora of structural morphologies, with tailed dsDNA phages being the most represented in public databases as of 2019. Other seemingly less common phages can package their ssDNA, ssRNA or dsRNA genome into tailless virions. Despite their relatively small genomes, phages also show tremendous genomic diversity and complex evolutionary relationships that do not obey traditional hierarchical phylogeny, due to pervasive mosaicism.
噬菌体是地球上最丰富、最多样的生物实体。这一开场白已成为许多病毒生态学家的最爱。据估计，地球上有 1031 个噬菌体1 ，在某些生态系统中，噬菌体的数量甚至超过细菌约十倍。从人类胃肠道到全球海洋，噬菌体存在于每一个已探明的生物群落中，而且还存在于令人吃惊的地方，如海洋基底2 和中世纪的粪便化石标本3。在水生环境中，噬菌体被证明在生物地球化学循环中发挥着重要作用，它们通过杀死细菌（即病毒分流1）使碳流短路。噬菌体在人类肠道中也是重要的调节剂，它们在肠道中主要过着溶菌生活，这会影响细菌宿主的生理和新陈代谢4。除了无处不在之外，噬菌体还表现出大量的结构形态，截至 2019 年，在公共数据库中，有尾 dsDNA 噬菌体的数量最多。其他看似不太常见的噬菌体可以将其 ssDNA、ssRNA 或 dsRNA 基因组包装成无尾病毒。尽管噬菌体的基因组相对较小，但由于普遍存在镶嵌现象，它们也表现出巨大的基因组多样性和复杂的进化关系，不服从传统的分级系统进化。
Much of our knowledge of phage diversity has been redrawn following the advancements in large-scale viral metagenomics and culturing efforts. In recent years, scientists have discovered phages with a genome size nearly ten times larger than average5. Non-tailed dsDNA6,7 and ssDNA8,9 phages are increasingly identified and even perhaps dominant in some biomes. Thousands of viral sequences have been identified from metagenomic projects, yet most of them share no detectable homology with reference phages10,11. One feature that was certainly emphasized by metagenomics is the exceptional viral diversity at the genomic level.
随着大规模病毒元基因组学和培养工作的进展，我们对噬菌体多样性的认识也有了很大改观。近年来，科学家们发现噬菌体的基因组大小比平均水平大近 10 倍5 。非尾状 dsDNA6,7 和 ssDNA8,9 噬菌体越来越多地被发现，甚至可能在某些生物群落中占主导地位。元基因组项目已鉴定出数千个病毒序列，但其中大多数与参考噬菌体没有可检测到的同源性10,11。当然，元基因组学强调的一个特点是病毒在基因组水平上的特殊多样性。
This review will focus on phage (viruses infecting bacteria) diversity and will explore four levels of organization. First, we present their unique morphologies and the structural proteins that make up these viral particles. Second, we examine the genomic diversity and scarceness in gene content similarities. From these two analyses emerges a contradiction: even when no sequence homology exists between morphologically distinct phages, some viral proteins still show conservation at the structural level. Third, we evaluate viral diversity at the community level, by comparing phage abundance and composition in various ecosystems. Recent progress in viral metagenomics has broadened our view of phage abundance and diversity, especially in marine environments. Lastly, we explore gene exchanges between phages, which generate mosaicity and diversification, and illustrate that bacterial viruses are interconnected through a complex web.
本综述将重点讨论噬菌体（感染细菌的病毒）的多样性，并将探讨四个层次的组织结构。首先，我们将介绍噬菌体的独特形态以及构成这些病毒颗粒的结构蛋白。其次，我们研究基因组的多样性和基因内容相似性的稀缺性。通过这两项分析，我们发现了一个矛盾：即使形态上不同的噬菌体之间不存在序列同源性，一些病毒蛋白在结构层面上仍然显示出保护性。第三，我们通过比较不同生态系统中噬菌体的丰度和组成，评估了群落层面的病毒多样性。病毒元基因组学的最新进展拓宽了我们对噬菌体丰度和多样性的视野，尤其是在海洋环境中。最后，我们探讨了噬菌体之间的基因交换，这种交换产生了镶嵌性和多样性，并说明细菌病毒通过复杂的网络相互关联。