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The evolution of Ebola virus: Insights from the 2013–2016 epidemic

Abstract

The 2013–2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude and changed our perspective on this lethal but sporadically emerging virus. This outbreak also marked the beginning of large-scale real-time molecular epidemiology. Here, we show how evolutionary analyses of Ebola virus genome sequences provided key insights into virus origins, evolution and spread during the epidemic. We provide basic scientists, epidemiologists, medical practitioners and other outbreak responders with an enhanced understanding of the utility and limitations of pathogen genomic sequencing. This will be crucially important in our attempts to track and control future infectious disease outbreaks.

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Figure 1: Evolution of EBOV during the 2013–2016 outbreak showing the extent and location of virus sampling.
Figure 2: Evolutionary rates of EBOV compared to those of other RNA viruses.
Figure 3: Examples of violations of the Ebola virus molecular clock.
Figure 4: Illustration of different measures of genomic variation.

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References

  1. Baize, S. et al. Emergence of Zaire Ebola virus disease in Guinea. N. Engl. J. Med. 371, 1418–1425 (2014).The first paper to describe the emergence of EBOV Makona in Guinea in December 2013, providing the sequences of three full-length viral genomes.

    Article  CAS  PubMed  Google Scholar 

  2. Gire, S. K. et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 345, 1369–1372 (2014).Obtained the first large-scale, near-real-time EBOV genomic data from 78 patients in Sierra Leone, which provided critical insights into virus spread during the early stages of the epidemic.

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  3. Park, D. J. et al. Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone. Cell 161, 1516–1526 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Andersen, K. G. et al. Clinical sequencing uncovers origins and evolution of Lassa virus. Cell 162, 738–750 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kuhn, J. H. et al. Nomenclature- and database-compatible names for the two Ebola virus variants that emerged in Guinea and the Democratic Republic of the Congo in 2014. Viruses 6, 4760–4799 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  6. WHO. Statement on the 1st meeting of the IHR Emergency Committee on the 2014 Ebola outbreak in West Africa. WHO Media Centrehttp://www.who.int/mediacentre/news/statements/2014/ebola-20140808/en/(2014)

  7. Ebola Situation Report, W. H. O. Ebola virus disease outbreak http://apps.who.int/ebola/current-situation/ebola-situation-report-30-march-2016 (2016)

  8. Nichol, S. T. et al. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science 262, 914–917 (1993)

    Article  CAS  ADS  PubMed  Google Scholar 

  9. Holmes, E. C. et al. The molecular epidemiology of human immunodeficiency virus type 1 in Edinburgh. J. Infect. Dis. 171, 45–53 (1995)

    Article  CAS  PubMed  Google Scholar 

  10. Tsui, S. K., Chim, S. S. & Lo, Y. M. Coronavirus genomic-sequence variations and the epidemiology of the severe acute respiratory syndrome. N. Engl. J. Med. 349, 187–188 (2003)

    Article  CAS  PubMed  Google Scholar 

  11. Ghedin, E. et al. Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution. Nature 437, 1162–1166 (2005)

    Article  CAS  ADS  PubMed  Google Scholar 

  12. Garten, R. J. et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 325, 197–201 (2009)

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  13. Chiu, C. Y. Viral pathogen discovery. Curr. Opin. Microbiol. 16, 468–478 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shendure, J. & Ji, H. Next-generation DNA sequencing. Nat. Biotechnol. 26, 1135–1145 (2008)

    Article  CAS  PubMed  Google Scholar 

  15. Metzker, M. L. Sequencing technologies—the next generation. Nat. Rev. Genet. 11, 31–46 (2010)

    Article  CAS  PubMed  Google Scholar 

  16. Mardis, E. R. Next-generation sequencing platforms. Annu. Rev. Anal. Chem. 6, 287–303 (2013)

    Article  CAS  Google Scholar 

  17. Hoenen, T. et al. Virology. Mutation rate and genotype variation of Ebola virus from Mali case sequences. Science 348, 117–119 (2015)

    Article  CAS  ADS  PubMed  Google Scholar 

  18. Bell, A. et al. Genome sequence analysis of Ebola virus in clinical samples from three British healthcare workers, August 2014 to March 2015. Euro Surveill. 20, 21131 (2015)

    Article  PubMed  Google Scholar 

  19. Kugelman, J. R. et al. Monitoring of Ebola virus Makona evolution through establishment of advanced genomic capability in Liberia. Emerg. Infect. Dis. 21, 1135–1143 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Simon-Loriere, E. et al. Distinct lineages of Ebola virus in Guinea during the 2014 West African epidemic. Nature 524, 102–104 (2015)

    Article  CAS  ADS  PubMed  Google Scholar 

  21. Carroll, M. W. et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature 524, 97–101 (2015).The first study to obtain a large EBOV sequence data set collected over multiple outbreaks, providing insights into the phylogenetic relationship between EBOV outbreak variants as well as other filoviruses.

    Article  CAS  ADS  PubMed  Google Scholar 

  22. Tong, Y. G. et al. Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone. Nature 524, 93–96 (2015)

    Article  CAS  PubMed  Google Scholar 

  23. Smits, S. L. et al. Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015. Euro Surveill. 20, 30035 (2015)

    Article  Google Scholar 

  24. Ladner, J. T. et al. Evolution and spread of Ebola virus in Liberia, 2014–2015. Cell Host Microbe 18, 659–669 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Quick, J. et al. Real-time, portable genome sequencing for Ebola surveillance. Nature 530, 228–232 (2016).Implemented real-time sequencing in Guinea using the Oxford Nanopore MinION technology, which enabled EBOV genomic sequence data to be obtained within hours or days of cases being detected.

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  26. Arias, A. et al. Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases. Virus Evol. 2, vew016(2016).The largest single study of EBOV genomics to date. Implemented real-time sequencing in Sierra Leone using the Thermo Fisher Ion Torrent platform, which enabled EBOV genomic sequence data to be obtained within days of cases being detected.

    Article  MathSciNet  PubMed  PubMed Central  Google Scholar 

  27. Matranga, C. B. et al. Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples. Genome Biol. 15, 519 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Woolhouse, M. E., Rambaut, A. & Kellam, P. Lessons from Ebola: improving infectious disease surveillance to inform outbreak management. Sci. Transl. Med. 7, 307rv5 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  29. Neher, R. A. & Bedford, T. Nextflu: real-time tracking of seasonal influenza virus evolution in humans. Bioinformatics 31, 3546–3548 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bedford, T. & Neher, R. A. NextStrain—real-time analysis of Ebola virus evolution. NextStrain http://ebola.nextstrain.org/ (2015)

  31. Lewis, J. A. et al. Phylogenetic relationships of dengue-2 viruses. Virology 197, 216–224 (1993)

    Article  CAS  PubMed  Google Scholar 

  32. Ray, S. C., Arthur, R. R., Carella, A., Bukh, J. & Thomas, D. L. Genetic epidemiology of hepatitis C virus throughout Egypt. J. Infect. Dis. 182, 698–707 (2000)

    Article  CAS  PubMed  Google Scholar 

  33. WHO. WHO experts consultation on Ebola Reston pathogenicity in humans. Emergencies Preparedness, Response http://www.who.int/csr/resources/publications/WHO_HSE_EPR_2009_2/en/ (2015)

  34. Leroy, E. M. et al. Fruit bats as reservoirs of Ebola virus. Nature 438, 575–576 (2005).Obtained sequence information from three species of fruit bats collected during the 2001–2003 EVD outbreak in Gabon to provide the first convincing evidence implicating fruit bats as a/the likely EBOV reservoir.

    Article  CAS  ADS  PubMed  Google Scholar 

  35. Leendertz, S. A., Gogarten, J. F., Düx, A., Calvignac-Spencer, S. & Leendertz, F. H. Assessing the evidence supporting fruit bats as the primary reservoirs for Ebola viruses. EcoHealth 13, 18–25 (2016)

    Article  PubMed  Google Scholar 

  36. Taylor, D. J., Leach, R. W. & Bruenn, J. Filoviruses are ancient and integrated into mammalian genomes. BMC Evol. Biol. 10, 193 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Taylor, D. J., Ballinger, M. J., Zhan, J. J., Hanzly, L. E. & Bruenn, J. A. Evidence that ebolaviruses and cuevaviruses have been diverging from marburgviruses since the Miocene. PeerJ 2, e556 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Report of an International Commission. Ebola haemorrhagic fever in Zaire, 1976. Bull. World Health Organ. 56, 271–293 (1978)

  39. WHO Ebola Response Team. Ebola virus disease in West Africa—the first 9 months of the epidemic and forward projections. N. Engl. J. Med. 371, 1481–1495 (2014)

  40. Kucharski, A. J. & Edmunds, W. J. Case fatality rate for Ebola virus disease in West Africa. Lancet 384, 1260 (2014)

    Article  PubMed  Google Scholar 

  41. CDC. Outbreaks chronology: Ebola virus disease. Outbreaks http://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html (2015)

  42. Marzi, A. et al. Delayed disease progression in Cynomolgus macaques infected with Ebola virus Makona strain. Emerg. Infect. Dis. 21, 1777–1783 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Schieffelin, J. S. et al. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N. Engl. J. Med. 371, 2092–2100 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Volz, E. & Pond, S. Phylodynamic analysis of Ebola virus in the 2014 Sierra Leone epidemic. PLoS Curr. 6, ecurrents.outbreaks.6f7025f1271821d4c815385b08f5f80e (2014)

  45. Alizon, S., Lion, S., Murall, C. L. & Abbate, J. L. Quantifying the epidemic spread of Ebola virus (EBOV) in Sierra Leone using phylodynamics. Virulence 5, 825–827 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  46. Althaus, C. L. Estimating the reproduction number of Ebola virus (EBOV) during the 2014 outbreak in West Africa. PLoS Curr. 6, ecurrents.outbreaks.91afb5e0f279e7f29e7056095255b288 (2014)

  47. Rosello, A. et al. Ebola virus disease in the Democratic Republic of the Congo, 1976-2014. eLife 4, e09015 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  48. Dudas, G. & Rambaut, A. Phylogenetic analysis of Guinea 2014 EBOV ebolavirus outbreak. PLoS Curr. 6, ecurrents.outbreaks.84eefe5ce43ec9dc0bf0670f7b8b417d (2014)

  49. Leroy, E. M. et al. Multiple Ebola virus transmission events and rapid decline of central African wildlife. Science 303, 387–390 (2004)

    Article  CAS  ADS  PubMed  Google Scholar 

  50. Wittmann, T. J. et al. Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants. Proc. Natl Acad. Sci. USA 104, 17123–17127 (2007)

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  51. Walsh, P. D., Biek, R. & Real, L. A. Wave-like spread of Ebola Zaire. PLoS Biol. 3, e371 (2005)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Carroll, S. A. et al. Molecular evolution of viruses of the family Filoviridae based on 97 whole-genome sequences. J. Virol. 87, 2608–2616 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Biek, R., Walsh, P. D., Leroy, E. M. & Real, L. A. Recent common ancestry of Ebola Zaire virus found in a bat reservoir. PLoS Pathog. 2, e90 (2006).Using previously available sequence data, this paper describes a strong link between EBOV found in bats and EBOV found in humans during outbreaks, suggesting common ancestry within the last three decades.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Drummond, A. J., Ho, S. Y., Phillips, M. J. & Rambaut, A. Relaxed phylogenetics and dating with confidence. PLoS Biol. 4, e88 (2006)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Sanchez, A., Trappier, S. G., Mahy, B. W., Peters, C. J. & Nichol, S. T. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc. Natl Acad. Sci. USA 93, 3602–3607 (1996)

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  56. Georges-Courbot, M. C. et al. Isolation and phylogenetic characterization of Ebola viruses causing different outbreaks in Gabon. Emerg. Infect. Dis. 3, 59–62 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Georges, A. J. et al. Ebola hemorrhagic fever outbreaks in Gabon, 1994–1997: epidemiologic and health control issues. J. Infect. Dis. 179 (Suppl. 1), S65–S75 (1999)

    Article  PubMed  Google Scholar 

  58. Rodriguez, L. L. et al. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J. Infect. Dis. 179 (Suppl. 1), S170–S176 (1999)

    Article  CAS  PubMed  Google Scholar 

  59. Grard, G. et al. Emergence of divergent Zaire ebola virus strains in Democratic Republic of the Congo in 2007 and 2008. J. Infect. Dis. 204 (Suppl. 3), S776–S784 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  60. Łuksza, M., Bedford, T. & Lässig, M. Epidemiological and evolutionary analysis of the 2014 Ebola virus outbreak. Preprint at: http://arxiv.org/pdf/1411.1722.pdf (2014)

  61. Holmes, E. C. The Evolution and Emergence of RNA Viruses. (Oxford Univ. Press, 2009)

  62. Osterholm, M. T. et al. Transmission of Ebola viruses: what we know and what we do not know. MBio 6, e00137 (2015)

    PubMed  PubMed Central  Google Scholar 

  63. Ponce De Leon-Rosales, S., Arredondo-Hernandez, R., Macias, A. & Wenzel, R. P. Ebola, through air or not through air: that is the question. Front. Public Health 2, 292 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  64. Leroy, E. M., Labouba, I., Maganga, G. D. & Berthet, N. Ebola in West Africa: the outbreak able to change many things. Clin. Microbiol. Infect. 20, O597–O599 (2014)

    Article  CAS  PubMed  Google Scholar 

  65. Osterholm, M. T. What we’re afraid to say about Ebola. NY Times (11 Sept. 2014)

  66. Basch, C. H., Basch, C. E. & Redlener, I. Coverage of the Ebola virus disease epidemic in three widely circulated United States newspapers: implications for preparedness and prevention. Health Promot. Perspect. 4, 247–251 (2014)

    PubMed  PubMed Central  Google Scholar 

  67. Callaway, E. M. Ebola’s fast evolution questioned. NATNEWS doi: 10.1038/nature.2015.17200 (2015)

  68. Vogel, G. A reassuring snapshot of Ebola. Science 347, 1407 (2015)

    Article  CAS  ADS  PubMed  Google Scholar 

  69. Saphire, E. O. New advances in the effort against Ebola. Cell Host Microbe 17, 545–547 (2015)

    Article  CAS  PubMed  Google Scholar 

  70. Liu, S. Q., Rayner, S. & Zhang, B. How Ebola has been evolving in West Africa. Trends Microbiol. 23, 387–388 (2015)

    Article  PubMed  CAS  Google Scholar 

  71. Ho, S. Y., Shapiro, B., Phillips, M. J., Cooper, A. & Drummond, A. J. Evidence for time dependency of molecular rate estimates. Syst. Biol. 56, 515–522 (2007)

    Article  PubMed  Google Scholar 

  72. Duchêne, S., Holmes, E. C. & Ho, S. Y. Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates. Proc. R. Soc. 281, 20140732(2014)

    Article  Google Scholar 

  73. Moya, A., Holmes, E. C. & González-Candelas, F. The population genetics and evolutionary epidemiology of RNA viruses. Nat. Rev. Microbiol. 2, 279–288 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Maganga, G. D. et al. Ebola virus disease in the Democratic Republic of Congo. N. Engl. J. Med. 371, 2083–2091 (2014)

    Article  CAS  PubMed  Google Scholar 

  75. Lam, T. T., Zhu, H., Chong, Y. L., Holmes, E. C. & Guan, Y. Puzzling origins of the Ebola outbreak in the Democratic Republic of the Congo, 2014. J. Virol. 89, 10130–10132 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Blackley, D. J. et al. Reduced evolutionary rate in reemerged Ebola virus transmission chains. Sci. Adv. 2, e1600378 (2016).Using EBOV sequencing from seven EVD cases collected during a ‘flare-up’ in Liberia, this study investigates how these cases were linked to individuals who had survived EVD and carried the virus as a persistent asymptomatic infection.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  77. Mate, S. E. et al. Molecular evidence of sexual transmission of Ebola virus. N. Engl. J. Med. 373, 2448–2454 (2015).Using a combination of epidemiological and sequence-based investigations, this study convincingly shows that EBOV is capable of sexual transmission many months after an EVD survivor was discharged from the hospital.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Malpica, J. M. et al. The rate and character of spontaneous mutation in an RNA virus. Genetics 162, 1505–1511 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Sanjuán, R., Nebot, M. R., Chirico, N., Mansky, L. M. & Belshaw, R. Viral mutation rates. J. Virol. 84, 9733–9748 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Domingo-Calap, P. & Sanjuán, R. Experimental evolution of RNA versus DNA viruses. Evolution 65, 2987–2994 (2011)

    Article  PubMed  Google Scholar 

  81. Kuhn, J. H. Filoviruses. A compendium of 40 years of epidemiological, clinical, and laboratory studies. Arch. Virol. Suppl. 20, 13–360 (2008)

    Article  PubMed  Google Scholar 

  82. Côté, M. et al. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature 477, 344–348 (2011)

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  83. Carette, J. E. et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477, 340–343 (2011)

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  84. Horimoto, T. & Kawaoka, Y. Influenza: lessons from past pandemics, warnings from current incidents. Nat. Rev. Microbiol. 3, 591–600 (2005)

    Article  CAS  PubMed  Google Scholar 

  85. Deen, G. F. et al. Ebola RNA persistence in semen of Ebola virus disease survivors—preliminary report. N. Engl. J. Med. (2015). 10.1056/NEJMoa1511410

  86. Christie, A. et al. Possible sexual transmission of Ebola virus—Liberia, 2015. MMWR Morb. Mortal. Wkly. Rep. 64, 479–481 (2015)

    Google Scholar 

  87. Fischer, R. J., Judson, S., Miazgowicz, K., Bushmaker, T. & Munster, V. J. Ebola virus persistence in semen ex vivo. Emerg. Infect. Dis. 22, 289–291 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  88. Thorson, A., Formenty, P., Lofthouse, C. & Broutet, N. Systematic review of the literature on viral persistence and sexual transmission from recovered Ebola survivors: evidence and recommendations. BMJ Open 6, e008859 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  89. Lemey, P., Rambaut, A., Drummond, A. J. & Suchard, M. A. Bayesian phylogeography finds its roots. PLOS Comput. Biol. 5, e1000520 (2009)

    Article  ADS  MathSciNet  PubMed  PubMed Central  CAS  Google Scholar 

  90. Stadler, T. et al. Estimating the basic reproductive number from viral sequence data. Mol. Biol. Evol. 29, 347–357 (2012)

    Article  CAS  PubMed  Google Scholar 

  91. Stadler, T., Kühnert, D., Rasmussen, D. A. & du Plessis, L. Insights into the early epidemic spread of Ebola in Sierra Leone provided by viral sequence data. PLoS Curr. 6, ecurrents.outbreaks.02bc6d927ecee7bbd33532ec8ba6a25f (2014).Using sequence data from 72 EVD cases from Sierra Leone, this study utilized phylodynamic analyses to estimate several epidemiological parameters, obtaining an R 0 of around 2.18.

  92. Stadler, T. & Bonhoeffer, S. Uncovering epidemiological dynamics in heterogeneous host populations using phylogenetic methods. Phil. Trans. R. Soc. Lond. B 368, 20120198 (2013)

    Article  Google Scholar 

  93. Hoenen, T. et al. Nanopore sequencing as a rapidly deployable Ebola outbreak tool. Emerg. Infect. Dis. 22, 331–334 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Yozwiak, N. L. et al. Roots, not parachutes: research collaborations combat outbreaks. Cell 166, 5–8 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Poon, L. L. et al. Quantifying influenza virus diversity and transmission in humans. Nat. Genet. 48, 195–200 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Stack, J. C., Murcia, P. R., Grenfell, B. T., Wood, J. L. & Holmes, E. C. Inferring the inter-host transmission of influenza A virus using patterns of intra-host genetic variation. Proc. R. Soc. 280, 20122173 (2013)

    Article  CAS  Google Scholar 

  97. Drummond, A. J., Suchard, M. A., Xie, D. & Rambaut, A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 29, 1969–1973 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Hoenen, T. et al. Erratum: Mutation rate and genotype variation of Ebola virus from Mali case sequences. Science 348, aac5674 (2015)

    Article  CAS  Google Scholar 

  99. Stamatakis, A., Ludwig, T. & Meier, H. RAxML-III: a fast program for maximum likelihood-based inference of large phylogenetic trees. Bioinformatics 21, 456–463 (2005)

    Article  CAS  PubMed  Google Scholar 

  100. Guindon, S. & Gascuel, O. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52, 696–704 (2003)

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank all the African doctors, nurses, scientists, and outbreak responders who worked to control the 2013–2016 EVD epidemic, some of whom tragically died in the process. We also thank the EBOV genome sequence data producers for making their data publicly available, S. Schaffner for suggestions and reading of the manuscript, and L. M. Carvalho for donating evolutionary rate data. E.C.H. is funded by an NHMRC Australia Fellowship (AF30). G.D. is supported by EU (FP7/2007-2013) Grant Agreement no. 278433-PREDEMICS and the Mahan Postdoctoral Fellowship from the Computational Biology Program at Fred Hutchinson Cancer Research Center. A.R. is supported by EU (FP7/2007-2013) Grant Agreement no. 278433-PREDEMICS, H2020 Grant Agreement no. 643476-COMPARE, and a Wellcome Trust Strategic Award (VIZIONS; 093724). K.G.A. is a PEW Biomedical Scholar, and his work is supported by an NIH National Center for Advancing Translational Studies Clinical and Translational Science Award UL1TR001114, and NIAID contract HHSN272201400048C.

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Nature thanks C. Drosten, P. Lemey, G. Palacios and T. Sadler for their contribution to the peer review of this work.

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Holmes, E., Dudas, G., Rambaut, A. et al. The evolution of Ebola virus: Insights from the 2013–2016 epidemic. Nature 538, 193–200 (2016). https://doi.org/10.1038/nature19790

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