Department of Biology, University of Waterloo, 200 University Ave. West., Waterloo, ON N2L 3G1, Canada.
Viruses. 2023 May 5;15(5):1116. doi: 10.3390/v15051116.
Phycodnaviridae are large double-stranded DNA viruses, which facilitate studies of host-virus interactions and co-evolution due to their prominence in algal infection and their role in the life cycle of algal blooms. However, the genomic interpretation of these viruses is hampered by a lack of functional information, stemming from the surprising number of hypothetical genes of unknown function. It is also unclear how many of these genes are widely shared within the clade. Using one of the most extensively characterized genera, Coccolithovirus, as a case study, we combined pangenome analysis, multiple functional annotation tools, AlphaFold structural modeling, and literature analysis to compare the core and accessory pangenome and assess support for novel functional predictions. We determined that the Coccolithovirus pangenome shares 30% of its genes with all 14 strains, making up the core. Notably, 34% of its genes were found in at most three strains. Core genes were enriched in early expression based on a transcriptomic dataset of Coccolithovirus EhV-201 algal infection, were more likely to be similar to host proteins than the non-core set, and were more likely to be involved in vital functions such as replication, recombination, and repair. In addition, we generated and collated annotations for the EhV representative EhV-86 from 12 different annotation sources, building up information for 142 previously hypothetical and putative membrane proteins. AlphaFold was further able to predict structures for 204 EhV-86 proteins with a modelling accuracy of good-high. These functional clues, combined with generated AlphaFold structures, provide a foundational framework for the future characterization of this model genus (and other giant viruses) and a further look into the evolution of the Coccolithovirus proteome.
噬藻体病毒科是大型双链 DNA 病毒，由于其在藻类感染中的突出地位及其在藻类大量繁殖的生命周期中的作用，促进了宿主-病毒相互作用和共同进化的研究。然而，由于大量具有未知功能的假定基因，这些病毒的基因组解释受到阻碍。也不清楚这些基因中有多少在进化枝内广泛共享。我们使用最广泛特征的一个属 Coccolithovirus 作为案例研究，结合泛基因组分析、多种功能注释工具、AlphaFold 结构建模和文献分析，比较核心和辅助泛基因组，并评估对新功能预测的支持。我们确定，Coccolithovirus 泛基因组与所有 14 株共享 30%的基因，构成核心。值得注意的是，其 34%的基因最多存在于三种菌株中。基于 Coccolithovirus EhV-201 藻类感染的转录组数据集，核心基因在早期表达中富集，与非核心基因相比，更有可能与宿主蛋白相似，并且更有可能参与复制、重组和修复等重要功能。此外，我们从 12 个不同的注释来源为 EhV 代表 EhV-86 生成和整理注释，为 142 个以前的假定和推定膜蛋白积累信息。AlphaFold 进一步能够对 204 个 EhV-86 蛋白进行建模，建模准确性为良好至高度。这些功能线索，结合生成的 AlphaFold 结构，为该模型属（和其他巨型病毒）的未来特征描述提供了基础框架，并进一步探讨了 Coccolithovirus 蛋白质组的进化。
