1887

Microbial Genomics logo

Volume 9, Issue 1

Analysis of variola virus molecular evolution suggests an old origin of the virus consistent with historical records Open Access

Abstract

Archaeovirology efforts provided a rich portrait of the evolutionary history of variola virus (VARV, the cause of smallpox), which was characterized by lineage extinctions and a relatively recent origin of the virus as a human pathogen (~1700 years ago, ya). This contrasts with historical records suggesting the presence of smallpox as early as 3500 ya. By performing an analysis of ancestry components in modern, historic, and ancient genomes, we unveil the progressive drifting of VARV lineages from a common ancestral population and we show that a small proportion of Viking Age ancestry persisted until the 18th century. After the split of the P-I and P-II lineages, the former experienced a severe bottleneck. With respect to the emergence of VARV as a human pathogen, we revise time estimates by accounting for the time-dependent rate phenomenon. We thus estimate that VARV emerged earlier than 3800 ya, supporting its presence in ancient societies, as pockmarked Egyptian mummies suggest.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): molecular dating , population structure , smallpox and Variola virus
Funding
This study was supported by the:
  • Ministero della Salute (Award Ricerca Corrente 2022)
    • Principle Award Recipient: ManuelaSironi
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000932
2023-01-09
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/mgen/9/1/mgen000932.html?itemId=/content/journal/mgen/10.1099/mgen.0.000932&mimeType=html&fmt=ahah

References

  1. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID et al. Smallpox and its eradication; 1988
  2. Esposito JJ, Sammons SA, Frace AM, Osborne JD, Olsen-Rasmussen M et al. Genome sequence diversity and clues to the evolution of variola (smallpox) virus. Science 2006; 313:807–812 [View Article]
     [Google Scholar]
  3. Simpson K, Heymann D, Brown CS, Edmunds WJ, Elsgaard J et al. Human monkeypox - after 40 years, an unintended consequence of smallpox eradication. Vaccine 2020; 38:5077–5081 [View Article]
     [Google Scholar]
  4. Thèves C, Crubézy E, Biagini P. History of smallpox and its spread in human populations. Microbiol Spectr 2016; 4: [View Article]
     [Google Scholar]
  5. Mühlemann B, Vinner L, Margaryan A, Wilhelmson H, de la Fuente Castro C. Diverse variola virus (smallpox) strains were widespread in northern Europe in the viking age. Science 2020; 369:eaaw8977 [View Article]
     [Google Scholar]
  6. Duggan AT, Perdomo MF, Piombino-Mascali D, Marciniak S, Poinar D et al. 17th Century variola virus reveals the recent history of smallpox. Curr Biol 2016; 26:3407–3412 [View Article]
     [Google Scholar]
  7. Ferrari G, Neukamm J, Baalsrud HT, Breidenstein AM, Ravinet M et al. Variola virus genome sequenced from an eighteenth-century museum specimen supports the recent origin of smallpox. Philos Trans R Soc Lond B Biol Sci 2020; 375:20190572 [View Article]
     [Google Scholar]
  8. Ghafari M, Simmonds P, Pybus OG, Katzourakis A. A mechanistic evolutionary model explains the time-dependent pattern of substitution rates in viruses. Curr Biol 2021; 31:4689–4696 [View Article] [PubMed]
     [Google Scholar]
  9. Simmonds P, Aiewsakun P, Katzourakis A. Prisoners of war - host adaptation and its constraints on virus evolution. Nat Rev Microbiol 2019; 17:321–328 [View Article] [PubMed]
     [Google Scholar]
  10. Pajer P, Dresler J, Kabíckova H, Písa L, Aganov P et al. Characterization of two historic smallpox specimens from a Czech museum. Viruses 2017; 9:200 [View Article]
     [Google Scholar]
  11. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 2013; 30:772–780 [View Article] [PubMed]
     [Google Scholar]
  12. Watterson GA. On the number of segregating sites in genetical models without recombination. Theor Popul Biol 1975; 7:256–276 [View Article] [PubMed]
     [Google Scholar]
  13. Nei M, Li WH. Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci 1979; 76:5269–5273 [View Article]
     [Google Scholar]
  14. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 1989; 123:585–595 [View Article]
     [Google Scholar]
  15. Pfeifer B, Wittelsbürger U, Ramos-Onsins SE, Lercher MJ. PopGenome: an efficient Swiss army knife for population genomic analyses in R. Mol Biol Evol 2014; 31:1929–1936 [View Article] [PubMed]
     [Google Scholar]
  16. Boni MF, Posada D, Feldman MW. An exact nonparametric method for inferring mosaic structure in sequence triplets. Genetics 2007; 176:1035–1047 [View Article]
     [Google Scholar]
  17. Lam HM, Ratmann O, Boni MF. Improved algorithmic complexity for the 3SEQ recombination detection algorithm. Mol Biol Evol 2018; 35:247–251 [View Article]
     [Google Scholar]
  18. Haubold B, Hudson RR. LIAN 3.0: detecting linkage disequilibrium in multilocus data. Linkage analysis. Bioinformatics 2000; 16:847–848 [View Article]
     [Google Scholar]
  19. Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics 2000; 155:945–959 [View Article]
     [Google Scholar]
  20. Falush D, Stephens M, Pritchard JK. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 2003; 164:1567–1587 [View Article]
     [Google Scholar]
  21. Wang J. The computer program structure for assigning individuals to populations: easy to use but easier to misuse. Mol Ecol Resour 2017; 17:981–990 [View Article] [PubMed]
     [Google Scholar]
  22. Evanno G, Regnaut S, Goudet J. Detecting the number of clusters of individuals using the software STRUCTURE: a simulation study. Mol Ecol 2005; 14:2611–2620 [View Article] [PubMed]
     [Google Scholar]
  23. Earl DA. BM STRUCTURE HARVESTER: a website and program for visualizing STRUCTURE output and implementing the Evanno method. Conservation Genet Resour 2012; 4:359–361 [View Article]
     [Google Scholar]
  24. Kopelman NM, Mayzel J, Jakobsson M, Rosenberg NA, Mayrose I. Clumpak: a program for identifying clustering modes and packaging population structure inferences across K. Mol Ecol Resour 2015; 15:1179–1191 [View Article]
     [Google Scholar]
  25. Aiewsakun P, Katzourakis A. Time-Dependent Rate Phenomenon in Viruses. J Virol 2016; 90:7184–7195 [View Article] [PubMed]
     [Google Scholar]
  26. Porter AF, Duggan AT, Poinar HN, Holmes EC. Comment: characterization of two historic smallpox specimens from a Czech museum. Viruses 2017; 9:276 [View Article]
     [Google Scholar]
  27. Suchard MA, Lemey P, Baele G, Ayres DL, Drummond AJ et al. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evol 2018; 4:vey016 [View Article]
     [Google Scholar]
  28. Rambaut A, Drummond AJ, Xie D, Baele G, Suchard MA. Posterior summarization in bayesian phylogenetics using tracer 1.7. Syst Biol 2018; 67:901–904 [View Article]
     [Google Scholar]
  29. Correa RL, Bruckner FP, de Souza Cascardo R, Alfenas-Zerbini P. The role of F-box proteins during viral infection. Int J Mol Sci 2013; 14:4030–4049 [View Article]
     [Google Scholar]
  30. Ingham RJ, Loubich Facundo F, Dong J. Poxviral ANKR/F-box proteins: substrate adapters for ubiquitylation and more. Pathogens 2022; 11:875 [View Article]
     [Google Scholar]
  31. Schweneker M, Lukassen S, Späth M, Wolferstätter M, Babel E et al. The vaccinia virus O1 protein is required for sustained activation of extracellular signal-regulated kinase 1/2 and promotes viral virulence. J Virol 2012; 86:2323–2336 [View Article] [PubMed]
     [Google Scholar]
  32. Alcamí A. Was smallpox a widespread mild disease?. Science 2020; 369:376–377 [View Article]
     [Google Scholar]
  33. Bergna A, Ventura CD, Marzo R, Ciccozzi M, Galli M et al. Phylogeographical and evolutionary history of variola major virus; a question of timescales?. Infez Med 2022; 30:109–118 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000932
Loading
Analysis of variola virus molecular evolution suggests an old origin of the virus consistent with historical records
M Gen 9, 000932 (2023); https://doi.org/10.1099/mgen.0.000932
/content/journal/mgen/10.1099/mgen.0.000932
/content/journal/mgen/10.1099/mgen.0.000932
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error