Article

The evolutionary history of vertebrate RNA viruses

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Abstract

Our understanding of the diversity and evolution of vertebrate RNA viruses is largely limited to those found in mammalian and avian hosts and associated with overt disease. Here, using a large-scale meta-transcriptomic approach, we discover 214 vertebrate-associated viruses in reptiles, amphibians, lungfish, ray-finned fish, cartilaginous fish and jawless fish. The newly discovered viruses appear in every family or genus of RNA virus associated with vertebrate infection, including those containing human pathogens such as influenza virus, the Arenaviridae and Filoviridae families, and have branching orders that broadly reflected the phylogenetic history of their hosts. We establish a long evolutionary history for most groups of vertebrate RNA virus, and support this by evaluating evolutionary timescales using dated orthologous endogenous virus elements. We also identify new vertebrate-specific RNA viruses and genome architectures, and re-evaluate the evolution of vector-borne RNA viruses. In summary, this study reveals diverse virus–host associations across the entire evolutionary history of the vertebrates.

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Acknowledgements

This study was supported by the Special National Project on Research and Development of Key Biosafety Technologies (2016YFC1201900, 2016YFC1200101) and the National Natural Science Foundation of China (Grants 81672057, 81611130073). E.C.H. and M.S. are funded by an ARC Australian Laureate Fellowship to E.C.H. (FL170100022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank students at the Zoonosis branch of the China CDC, especially W.-C. Wu, J.-W. Shao, C.-X. Li, J.-J. Guo and K.-L. Song for assistance with virus and host sequence confirmation, and we thank B. Yu for help with the collection of animal samples. We acknowledge the University of Sydney high-performance computing (HPC) service at The University of Sydney for providing resources that have contributed to the research results reported within this paper

Reviewer information

Nature thanks A. Rambaut and M. Worobey for their contribution to the peer review of this work.

Author information

Author notes

  1. These authors contributed equally: Mang Shi, Xian-Dan Lin, Xiao Chen, Jun-Hua Tian.

Affiliations

  1. State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

    • Mang Shi
    • , Liang-Jun Chen
    • , Kun Li
    • , Wen Wang
    • , Edward C. Holmes
    •  & Yong-Zhen Zhang
  2. Shanghai Public Health Clinical Center & Institute of Biomedical Sciences, Fudan University, Shanghai, China

    • Mang Shi
    • , Edward C. Holmes
    •  & Yong-Zhen Zhang
  3. Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia

    • Mang Shi
    • , John-Sebastian Eden
    •  & Edward C. Holmes
  4. Wenzhou Center for Disease Control and Prevention, Wenzhou, China

    • Xian-Dan Lin
    •  & Li Liu
  5. College of Marine Sciences, South China Agricultural University, Guangzhou, China

    • Xiao Chen
  6. Wuhan Center for Disease Control and Prevention, Wuhan, China

    • Jun-Hua Tian
  7. Yancheng Center for Disease Control and Prevention, Yancheng, China

    • Jin-Jin Shen

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Contributions

M.S. and Y.-Z.Z. conceived and designed the study. M.S., X.-D.L., X.C., J.-H.T., K.L., L.-J.C., J.-J.S., L.L. and Y.-Z.Z. organized field work, and collected samples. M.S., X.-D.L., X.C., J.-H.T., K.L., L.-J.C., W.W., J.-J.S., L.L. and Y.-Z.Z. performed experiments. M.S., J.-S.E., E.C.H. and Y.-Z.Z. analysed data. M.S., E.C.H. and Y.-Z.Z. wrote the paper with input from all authors. Y.-Z.Z. led the study.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Yong-Zhen Zhang.

Extended data figures and tables

  1. Extended Data Fig. 1 Phylogenetic positions of vertebrate-associated positive-sense and double-stranded RNA viruses within the broader diversity of RNA viruses.

    Phylogenies were estimated using a maximum likelihood method and midpoint-rooted for clarity only. Viruses discovered here are labelled with solid black circles. The name of the major clade (phylogeny) is shown at the top of each tree, and taxonomic names are shown to the right. The vertebrate associated virus diversity is shaded in grey. All horizontal branch lengths are scaled to the number of amino acid substitutions per site.

  2. Extended Data Fig. 2 Phylogenetic positions of vertebrate-associated negative-sense RNA viruses within the broader diversity of RNA viruses.

    Phylogenies were estimated using a maximum likelihood method and midpoint-rooted for clarity only. Viruses discovered here are labelled with solid black circles. The name of the major clade (phylogeny) is shown at the top of each tree, and taxonomic names are shown to the right. The vertebrate associated virus diversity is shaded in grey. All horizontal branch lengths are scaled to the number of amino acid substitutions per site.

  3. Extended Data Fig. 3 The phylogenies of potentially new families of vertebrate-associated viruses.

    Viruses identified from vertebrate hosts are shaded with different colours. Sequences recovered from the Transcriptome Shotgun Assembly (TSA) database are marked with solid black diamonds, while those recovered from the Whole-Genome Shotgun (WGS) contigs database (that is, endogenous virus elements) are marked with open triangles. For vertebrate viruses, the relevant taxonomic and tissue information is provided in the sequence names.

  4. Extended Data Fig. 4 Evolutionary history of four groups of vector-borne RNA virus.

    Each phylogenetic tree was estimated using a maximum likelihood method. Within each phylogeny, the viruses newly identified here are marked with solid black circles, the vertebrate host groups are indicated by different colours, and the vector symbol is shown next to viruses known to be transmitted by vectors. The name of the virus family or genus is shown at the top of each phylogeny, and the lower level virus taxonomic names are shown to the right.

  5. Extended Data Fig. 5 Evolution of vertebrate-associated negative-sense RNA virus genomes.

    Representative genomes from negative-sense RNA virus families/genera are shown. The regions that encode major functional proteins or protein domains are labelled on each of the genomes. Homologous regions within each family are connected with orange dotted lines. Schematic phylogenetic relationships are shown next to the genomes diagrams. Coverage plots are shown underneath novel genome structures. Reverse-complementary sequences are shown for negative-sense RNA viruses with complete termini. A Sanger sequencing chromatogram is shown at a GC-rich hairpin-forming region of the Wenling frogfish arenavirus 2 genome, in which the coverage drops substantially. Host associations are labelled to the right of tree using solid circles with different colours. Host associations and abbreviation of functional domains are described at the bottom of the figure.

  6. Extended Data Fig. 6 Evolution of vertebrate-associated positive-sense RNA virus genomes.

    Representative genomes from positive-sense RNA virus families or genera are shown. The regions that encode major functional proteins or protein domains are labelled on each of the genomes. Homologous regions within or between viral families are connected by orange dotted lines. Host associations are reflected in the colour of the virus names. Host association colour schemes and the abbreviations of functional domains are described at the bottom of the figure.

Supplementary information

  1. Supplementary Table 1

    This table contains the detailed information of each pool/library

  2. Reporting Summary

  3. Supplementary Table 2

    This table contains the detailed information on each virus discovered in this study

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