Petrone Mary E, Grove Joe, Mélade Julien, Mifsud Jonathon C O, Parry Rhys H, Marzinelli Ezequiel M, Holmes Edward C
Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Laboratory of Data Discovery for Health Limited, Hong Kong Special Administrative Region, China.
Proc Natl Acad Sci U S A. 2024 Jul 23;121(30):e2403805121. doi: 10.1073/pnas.2403805121. Epub 2024 Jul 17.
It is commonly held that there is a fundamental relationship between genome size and error rate, manifest as a notional "error threshold" that sets an upper limit on genome sizes. The genome sizes of RNA viruses, which have intrinsically high mutation rates due to a lack of mechanisms for error correction, must therefore be small to avoid accumulating an excessive number of deleterious mutations that will ultimately lead to population extinction. The proposed exceptions to this evolutionary rule are RNA viruses from the order (such as coronaviruses) that encode error-correcting exonucleases, enabling them to reach genome lengths greater than 40 kb. The recent discovery of large-genome flavi-like viruses (), which comprise genomes up to 27 kb in length yet seemingly do not encode exonuclease domains, has led to the proposal that a proofreading mechanism is required to facilitate the expansion of nonsegmented RNA virus genomes above 30 kb. Herein, we describe a ~40 kb flavi-like virus identified in a sponge metatranscriptome that does not encode a known exonuclease. Structural analysis revealed that this virus may have instead captured cellular domains associated with nucleic acid metabolism that have not been previously found in RNA viruses. Phylogenetic inference placed this virus as a divergent pesti-like lineage, such that we have provisionally termed it "Maximus pesti-like virus." This virus represents an instance of a flavi-like virus achieving a genome size comparable to that of the and demonstrates that RNA viruses have evolved multiple solutions to overcome the error threshold.
人们普遍认为基因组大小与错误率之间存在着根本关系，表现为一个设定基因组大小上限的概念性“错误阈值”。由于缺乏纠错机制，RNA病毒的突变率本来就很高，因此其基因组大小必须很小，以避免积累过多有害突变，最终导致种群灭绝。这一进化规则的例外情况是来自该目（如冠状病毒）的RNA病毒，它们编码纠错外切核酸酶，使其基因组长度能够超过40kb。最近发现的大基因组黄病毒样病毒（），其基因组长度可达27kb，但似乎不编码外切核酸酶结构域，这导致有人提出需要一种校对机制来促进非节段RNA病毒基因组扩展到30kb以上。在此，我们描述了在一种海绵元转录组中鉴定出的一种约40kb的黄病毒样病毒，它不编码已知的外切核酸酶。结构分析表明，这种病毒可能捕获了与核酸代谢相关的细胞结构域，而这些结构域以前在RNA病毒中从未发现过。系统发育推断将这种病毒置于一个不同的瘟病毒样谱系中，因此我们暂时将其命名为“最大瘟病毒样病毒”。这种病毒代表了一种黄病毒样病毒达到与该病毒相当的基因组大小的实例，并表明RNA病毒已经进化出多种解决方案来克服错误阈值。
