Distribution and abundance
分布和丰度
Phages in marine environments
海洋环境中的噬菌体
Marine phages are thought to play major roles in modulating microbial communities, generating genetic diversity, and influencing the nutrient cycle through bacterial mortality84. The critical role of marine phages can be attributed to their tremendous abundance and diversity. In a recent analysis combining 22 distinct marine surveys, 95% of viral abundance was observed to range from 105 to 107 virus-like particles (VLPs) per ml, with a median virus-to-microbial cell ratio of 10:185. Analyses of samples from six global ocean regions using quantitative transmission electron microscopy (qTEM)6 revealed a dominance of non-tailed viruses in the samples (Fig. 4a) (79%) followed by Myoviridae (14%), Podoviridae (6%) and Siphoviridae (1%). Interestingly, the morphological distribution did not vary consistently with depth or oceanic region6.
海洋噬菌体被认为在调节微生物群落、产生遗传多样性以及通过细菌死亡影响营养循环方面发挥着重要作用84。海洋噬菌体的关键作用可归因于其巨大的丰度和多样性。最近的一项分析结合了 22 项不同的海洋调查，观察到 95% 的病毒丰度介于每毫升 105 到 107 个病毒样颗粒（VLPs）之间，病毒与微生物细胞的中位比例为 10:185。利用定量透射电子显微镜（qTEM）6 对全球六个海洋区域的样本进行分析后发现，样本中主要是无尾病毒（图 4a）（79%），其次是肌病毒科（14%）、波多病毒科（6%）和虹彩病毒科（1%）。有趣的是，形态分布并不随深度或海洋区域而变化6。
Comparative genomic analyses of more than 100 Synechococcus-infecting cyanophages collected over 15 years revealed genomic clusters and sub-clusters that exhibited clear temporal and/or spatial patterns of abundance86. Viral tagging metagenomics confirmed that phages infecting Synechococcus are clustered into at least 26 discrete populations with relative abundances ranging from 0.06 to 18.2%82. Possibly, the most abundant and well-distributed phages are those infecting Pelagibacter, a host dominating marine surface bacterioplankton communities87. Indeed, pelagiphages were among the most abundant phages in metagenomic datasets along longitudinal and depth gradients from all oceans80. The isolation and genome sequencing of 31 phages that infect Cellulophaga baltica (Bacteroidetes)88 showed that cellulophage diversity was even higher than that observed for Synechococcus phages and comprised non-tailed dsDNA phages. Comparisons with existing metagenomic data also revealed that cellulophages are widespread in oceans, but in low numbers. More recently, a group of dsDNA non-tailed viruses called autolykiviruses, that were previously missed due to multiple methodological biases, were isolated7. Genomic sequencing of these new phages revealed that they were present in the genome of major bacterial phyla and in metagenomic datasets from the water column and sediments7.
对 15 年来收集到的 100 多种感染 Synechococcus 的蓝藻噬菌体进行的基因组比较分析表明，基因组集群和亚集群表现出明显的丰度时间和/或空间模式86。病毒标签元基因组学证实，感染 Synechococcus 的噬菌体至少分为 26 个离散种群，相对丰度从 0.06% 到 18.2% 不等82。最丰富且分布最广的噬菌体可能是那些感染天竺藻的噬菌体，天竺藻是海洋表层浮游细菌群落的主要宿主87。事实上，在各大洋纵深梯度的元基因组数据集中，海蛆噬菌体是最丰富的噬菌体之一80。对感染 Baltica Cellulophaga（类杆菌）的 31 种噬菌体进行分离和基因组测序88 表明，噬菌体的多样性甚至高于在 Synechococcus 噬菌体中观察到的多样性，而且包括非尾状 dsDNA 噬菌体。与现有元基因组数据的比较也显示，嗜纤维细菌在海洋中广泛存在，但数量较少。最近，一组名为自溶病毒（autolykiviruses）的 dsDNA 无尾病毒被分离出来，这些病毒之前由于多种方法的偏差而被遗漏7。对这些新噬菌体的基因组测序显示，它们存在于主要细菌门的基因组中，也存在于水体和沉积物的元基因组数据集中7。
Taxonomic analyses of 24 Mediterranean metagenomes from diverse geographical and ecological biomes reported the dominance of Caudovirales, with Myoviridae accounting for 67%- 96% of the viral reads detected (followed by Podoviridae and Siphoviridae), independently of the water depth89. The largest marine viral metagenomics study was recently published11, which surveyed 145 samples from the Tara research expedition, including 41 samples from the polar circle. The authors identified 195,728 viral populations, 90% of which could not be taxonomically annotated, and found that Caudovirales dominated the known sequences. They confirmed that phages in the ocean form discrete populations and identified potential drivers of phage diversity, such as nitrate levels, photosynthetically active radiation, and latitude.
对来自不同地理和生态生物群落的 24 个地中海元基因组进行的分类分析表明，Caudovirales 占主导地位，Myoviridae 占检测到的病毒读数的 67%-96%（其次是 Podoviridae 和 Siphoviridae），与水深无关89。最近发表的最大规模的海洋病毒元基因组学研究报告11 调查了来自塔拉研究考察队的 145 个样本，包括来自极圈的 41 个样本。作者确定了 195 728 个病毒种群，其中 90% 无法进行分类注释，并发现 Caudovirales 在已知序列中占主导地位。他们证实海洋中的噬菌体形成了离散的种群，并确定了噬菌体多样性的潜在驱动因素，如硝酸盐水平、光合有效辐射和纬度。
In addition to exhibiting various morphological compositions, phage communities in the ocean have different replication strategies according to seasonal variations. In the western Antarctic Peninsula90 and in the Canadian Arctic Shelf91, prophages dominate in the spring while lytic infections prevail in the summer. This fluctuation can be explained by the Kill-the-Winner hypothesis, which states that a high bacterial abundance (caused by favorable growth conditions in the summer) is coupled with a high rate of lytic infections92,93. This model was further extended with the Piggyback-the-Winner model, in which the lysogenic lifestyle is instead privileged at high bacterial densities94,95. This was first observed in coral reefs, where the virus-to-host ratio was low despite heavy microbial density94. Following those dynamics, the abundant hosts have been killed by phages or became resistant lysogens, which in turn decreases phage titers when no more hosts are available for replication. According to a recent review66, the new phages to occupy the niche are more likely to be descendants of a ‘royal family’, i.e. variants of the most abundant phages that overcame host resistance. The authors coined the term ‘royal family model’ to illustrate the persistence of dominant phages in aquatic ecosystems.
海洋中的噬菌体群落除了表现出不同的形态组成外，还因季节变化而采取不同的复制策略。在南极半岛西部90 和加拿大北极大陆架91 ，噬菌体在春季占主导地位，而溶菌感染则在夏季盛行。这种波动可以用 “杀死赢家假说”（Kill-the-Winner hypothesis）来解释，该假说认为高细菌丰度（由夏季有利的生长条件引起）与高溶菌性感染率相伴92,93。该模型进一步扩展为 “猪背-赢家”（Piggyback-the-Winner）模型，在该模型中，溶解性生活方式在细菌密度高时反而具有优势94,95。这首先是在珊瑚礁中观察到的，在珊瑚礁中，尽管微生物密度很高，但病毒与宿主的比例却很低94。根据这些动态变化，大量宿主被噬菌体杀死或成为抗性溶菌体，当没有更多宿主可供复制时，噬菌体的滴度就会下降。根据最近的一篇综述66 ，占据利基的新噬菌体更有可能是 “皇室家族 “的后代，即克服宿主抗性的最大量噬菌体的变种。作者创造了 “王室模式 “一词来说明优势噬菌体在水生生态系统中的持续存在。
Phages from the soil 土壤中的噬菌体
Compared to marine environments, soils are intrinsically diverse due in part to their wide compositional spectrum and spatial heterogeneity in terms of physicochemical properties. A recent meta-analysis of 24 soils indicated that viral abundance is highly variable and correlates with soil type, ranging from approximately 103 VLPs/g in desert soils to 109 VLPs/g in forest soils67 (Fig. 4b). TEM observations of different soil types reported the predominance of non-tailed particles over tailed phages, and higher morphological diversity in forest soils compared to agricultural soils, in some cases96,97. Metagenomics were also used to assess the richness and evenness of viral communities in prairie, desert and rainforest soils98. Similar phage sequences were observed in all of these soils but were significantly different from the dominant types found in marine or faecal samples. Metagenomic analyses of different Antarctic soils revealed that tailed phages were dominant in all samples, with the presence of Myoviridae and Siphoviridae inversely correlated99. Of note, samples with low- and medium-diversity were completely dominated by Siphoviridae signatures. Abiotic factors like pH and the altitude of the sampling site appeared to be the main drivers of viral community composition99.
与海洋环境相比，土壤具有固有的多样性，部分原因在于其广泛的成分谱和理化特性方面的空间异质性。最近对 24 种土壤进行的荟萃分析表明，病毒丰度变化很大，并与土壤类型相关，从沙漠土壤中的约 103 个 VLPs/克到森林土壤中的 109 个 VLPs/克67（图 4b）。对不同类型土壤的 TEM 观察显示，无尾颗粒比有尾噬菌体占优势，在某些情况下，森林土壤的形态多样性比农业土壤高96,97。元基因组学也被用来评估草原、沙漠和雨林土壤中病毒群落的丰富性和均匀性98。在所有这些土壤中都观察到了类似的噬菌体序列，但与海洋或粪便样本中发现的主要类型明显不同。对不同南极土壤进行的元基因组分析表明，尾状噬菌体在所有样本中都占主导地位，而 Myoviridae 和 Siphoviridae 的存在成反比99。值得注意的是，多样性较低和中等的样本完全以 Siphoviridae 为主。取样地点的 pH 值和海拔高度等非生物因素似乎是病毒群落组成的主要驱动因素99。
Phages from the human gut
人体肠道中的噬菌体
Phages are also highly abundant in the human gut microbiome with up to 108 VLPs/ml in faecal filtrates100 (Fig. 4c). Of note, phage titer was higher in gut mucosal biopsies (109 per biopsy), possibly due to the affinity of host-associated phages to bind and accumulate in the mucosal secretion101,102. TEM visualizations demonstrated that Caudovirales dominate the gut, with striking inter-individual differences in the composition of morphologies and types100. Since most of the bacteria residing in the gut are difficult to culture, metagenomic sequencing is mainly used to assess the complexity and diversity of gut phage populations. Recent analyses confirmed that a large majority of contigs that could be identified belonged to the Caudovirales order, but members of the Microviridae family were also detected75,103,104. It should be mentioned that contigs with taxonomic attribution were low, which highlights the importance of the viral dark matter. The composition of the human gut virome seems also highly specific and stable over time. The differences among individuals are the main sources of variation, despite the fact that a core set of phages was found in 20–50% of individuals75,76,103,104. The viral community can also evolve considerably during the first years of life, leading to an increased abundance of Microviridae8. Finally, phage distribution is also dependent on individual health status. For example, patients with Crohn’s disease and ulcerative colitis exhibit a distinct virome with a significantly increased number of Caudovirales phages compared to Microviridae105.
噬菌体在人类肠道微生物组中也非常丰富，粪便滤液中的 VLPs 高达 108 个/毫升100（图 4c）。值得注意的是，噬菌体滴度在肠道粘膜活检组织中更高（109 个/活检组织），这可能是由于宿主相关噬菌体与粘膜分泌物结合并积聚的亲和力101,102。TEM 图像显示，肠道中的主要细菌为 Caudovirales，其形态和类型组成在个体间存在显著差异100。由于肠道中的大多数细菌难以培养，元基因组测序主要用于评估肠道噬菌体种群的复杂性和多样性。最近的分析证实，大部分可识别的等位基因属于 Caudovirales 目，但也检测到了微小病毒科的成员75,103,104。值得一提的是，具有分类属性的等位基因较少，这凸显了病毒暗物质的重要性。人类肠道病毒组的组成似乎也具有高度特异性和长期稳定性。尽管在 20%-50%的个体中发现了一组核心噬菌体，但个体之间的差异是变异的主要来源75,76,103,104。在生命的最初几年，病毒群落也会发生很大变化，导致微小病毒科的数量增加8。最后，噬菌体的分布也取决于个体的健康状况。例如，克罗恩病和溃疡性结肠炎患者表现出独特的病毒群，与微小病毒科相比，腔肠动物噬菌体的数量明显增加105。