Institute for Integrative Systems Biology (I2SysBio)





Viral mutation rates


University of Valencia

Genetics Department





Virus experimental evolution (Sanjuán lab)

Click here to see publications in Google Scholar

    1. Andreu-Moreno I., Bou J.V., Sanjuán R. (2020). Cooperative nature of viral replication. Sci. Adv., accepted for publication.
    2. Siles Lucas M., González-Miguel J., Geller R., Sanjuán R., Pérez-Arévalo J., Martínez-Moreno A. (2020). Potential influence of helminth molecules on COVID-19 pathology. Trends Parasitol., accepted for publication.
    3. Bou J.V., Sanjuán R. (2020). Experimental evolution reveals a genetic basis for membrane-associated virus release. Mol. Biol. Evol., online ahead of print.
    4. Randazzo W., Cuevas-Ferrando E., Sanjuán R., Domingo-Calap P., Sánchez G. (2020). Metropolitan wastewater analysis for COVID-19 epidemiological surveillance. Int. J. Hyg. Envir. Heal. 230: 113621.
    5. Domingo-Calap P., Mora-Quilis L., Sanjuán R. (2020). Social bacteriophages. Microorganisms 8: 533.
    6. Anschau V., Sanjuán R. (2020). Fibrinogen gamma chain promotes aggregation of vesicular stomatitis virus in saliva. Viruses 12: 282.
    7. Domingo-Calap P., Sanjuán R. (2020). Social interactions among bacteriophages. In: Biocommunication of phages. Springer. p. 103-119.
    8. Domingo-Calap P., Beamud B., Mora-Quilis L., González-Candelas F., Sanjuán R. (2020). Isolation and characterization of two Klebsiella pneumoniae phages encoding divergent depolymerases. Int. J. Mol. Sci. 21: 3160.
    9. Segredo-Otero E., Sanjuán R. (2020). The role of spatial structure in the evolution of viral innate immunity evasion: A diffusion-reaction cellular automaton model. PLoS Comp. Biol. 16: e1007656.
    10. Domingo-Calap P., Beamud B., Vienne J., González-Candelas F., Sanjuán R. (2020). Isolation of four lytic phages infecting Klebsiella pneumoniae K22 clinical isolates from Spain. Int. J. Mol. Sci. 21: 425.
    11. Andreu-Moreno I., Sanjuán R. (2020). Collective viral spread mediated by virion aggregates promotes the evolution of defective interfering particles. mBio 11: e02156-19.
    12. Risso-Ballester J., Sanjuán R. (2019). High fidelity deep sequencing reveals no effect of ATM, ATR, and DNA-PK cellular DNA damage response pathways on adenovirus mutation rate. Viruses 11: E938.
    13. Bou J.V., Geller R., Sanjuán R. (2019). Membrane-associated enteroviruses undergo intercellular transmission as pools of sibling viral genomes. Cell Rep. 29: 714-723.
    14. Sanjuán R., Domingo-Calap P. (2019). Genetic Diversity and Evolution of Viral Populations. Encyclopedia of Virology, 4th Edition. Elsevier.
    15. Segredo-Otero E., Sanjuán R. (2019) The effect of genetic complementation on the fitness and diversity of viruses spreading as collective infectious units. Virus Res. 267: 41-48.
    16.  Sanjuán R., Thoulouze M.I. (2019). Why viruses sometimes disperse in groups. Virus Evol. 5: vez014.
    17. Domingo-Calap P., Segredo-Otero E., Durán-Moreno M., Sanjuán R. (2019). Social evolution of innate immunity evasion in a virus. Nat. Microbiol 4: 1006-1013.
    18. Cebriá-Mendoza M., Sanjuán R., Domingo-Calap P. (2019). Directed evolution of a mycobacteriophage. Antibiotics 8: E46.
    19. Leeks A., Sanjuán R., West S.A. (2019). The evolution of collective infectious units in viruses. Virus Res. 265: 94-101.
    20. Sanjuán R. (2018). Collective properties of viral infectivity. Curr. Opin. Virol. 33: 1-6. [author pdf]
    21. Patiño-Galindo J.Á., Domínguez F., Cuevas M.T., Delgado E., Sánchez M., Pérez-Álvarez L., Thomson M.M., Sanjuán R., González-Candelas F., Cuevas J.M. (2018). Genome-scale analysis of evolutionary rate and selection in a fast-expanding Spanish cluster of HIV-1 subtype F1. Infect. Genet. Evol. 66: 43-47. [author pdf]
    22. Andreu-Moreno I., Sanjuán R. (2018). Collective infection of cells by viral aggregates promotes early viral proliferation and reveals a cellular-level Allee effect. Curr. Biol. 28: 3212-3219. [author pdf]
    23. Leeks A., Segredo-Otero E.A., Sanjuán R., West S.A. (2018). Beneficial coinfection can promote within-host viral diversity. Virus Evol. 4: vey028.
    24. Benito J.M., Hillung J., Restrepo C., Cuevas J.M., León A., Ruiz-Mateos E., Palacios-Muñoz R., Górgolas M., Sanjuán R., Rallón N. (2018). Role of APOBEC3H in the viral control of HIV elite controller patients. Int. J. Med. Sci. 15:95-100.
    25. López-Carrasco A., Ballesteros C., Sentandreu V., Delgado S., Gago-Zachert S., Flores R., Sanjuán R. (2017). Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing. PLoS Pathog. 13:e10065.
    26. Díaz-Muñoz S.L., Sanjuán R., West S. (2017). Sociovirology: conflict, cooperation, and communication among viruses. Cell Host Microbe 22: 437-441.
    27. Cuevas J.M., Durán-Moreno M., Sanjuán R. (2017). Multi-virion infectious units arise from free viral particles in an enveloped virus.  Nat. Microbiol. 2: 17078.
    28. Sanjuán R. (2017). Collective infectious units in  viruses. Trends Microbiol. 25:402-412

    29. Risso-Ballester J., Cuevas J.M., Sanjuán R. (2016). Genome-wide estimation of the spontaneous mutation rate of human adenovirus 5 by high-fidelity deep sequencing.  PLoS Pathog. 12:e1006013.
    30. Pereira-Gómez M., Bou J.V., Andreu I., Sanjuán R. (2016). Lamivudine/Adefovir treatment increases the rate of spontaneous mutation of hepatitis B virus in patients. PLoS One 11: e0163363.
    31. Sanjuán R., Domingo-Calap P. (2016). Mechanisms of viral mutation. Cell Mol Life Sci. 73:4433-4448.
    32. Geller R., Estada U., Peris J.B., Andreu I., Bou J.-V., Garijo R., Cuevas J.M., Sabariegos R., Mas A., Sanjuán R. (2016). Highly heterogeneous mutation rates in the hepatitis C virus genome. Nat. Microbiol. 1: 16045. Available at:
    33. Cuevas J.M., Combe M., Torres-Puente M., Garijo R., Guix S., Buesa J., Rodríguez-Díaz J., Sanjuán R. (2016). Human norovirus hyper-mutation revealed by ultra-deep sequencing. Infect. Genet. Evol., 41: 233-239.
    34. Garijo R, Cuevas J.M., Briz A., Sanjuán R. (2016). Constrained evolvability of interferon suppression in an RNA virus. Sci. Reports 6: 24722.
    35. Sanjuán R., Pereira-Gómez, M., Risso, J. Genome instability in DNA viruses (2016) in: Genome Stability (Eds: I. Kovalchuk, O. Kovalchuk). Elsevier.
    36. Combe M., Garijo R., Geller R., Cuevas J.M., Sanjuán R. (2015). Single-cell analysis of RNA virus infection identifies multiple genetically diverse viral genomes within single infectious units. Cell Host Microbe 18: 424-432
    37. Geller R., Domingo-Calap P., Cuevas J.M., Rossolillo P., Negroni M., Sanjuán R. (2015). The external domains of the HIV-1 envelope are a mutational cold spot. Nat. Commun. 6: 8571.
    38. Cuevas J.M., Geller R., Garijo R., López-Aldeguer J., Sanjuán R. (2015). Extremely high mutation rate of HIV-1 in vivo. PLoS Biol. 13:e1002251.
    39. Sanjuán R. Viral mutation rates (2015) in: Virus Evolution: Current Research and Future Perspectives (Eds: S.C. Weaver, M. Denison, M. Roossinck, M. Vignuzzi). Caister Academic Press.
    40. Pereira-Gómez M., Sanjuán R. (2015). Effect of mismatch repair on the mutation rate of bacteriophage fX174. Virus Evol. 1: vev010.
    41. Hernández-Alonso P., Garijo R., Cuevas J.M., Sanjuán R. (2015). Experimental evolution of an RNA virus in cells with innate immunity defects. Virus Evol. 1: vev008.
    42. Sanjuán R., Grdzelishvili V.Z. (2015). Evolution of oncolytic viruses. Curr. Opin .Virol. 13: 1-5.
    43. Garijo R., Hernández-Alonso P., Rivas C., Diallo J.S., Sanjuán R. (2014). Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells. PLoS One 9:e102365.
    44. Flores R., Gago-Zachert S., Serra P., Sanjuán R., Elena SF. (2014). Viroids: survivors from the RNA world? Annu. Rev. Microbiol. 68: 395-414.
    45. Cabanillas L., Sanjuán R., Lázaro E. (2014). Changes in protein domains outside the catalytic site of the bacteriophage Qβ replicase reduce the mutagenic effect of 5-azacytidine. J. Virol. 88: 10480-10487.
    46. Pereira-Gómez M., Sanjuán R. (2014). Delayed lysis confers resistance to the nucleoside analogue 5-fluorouracil and alleviates mutation accumulation in the single-stranded DNA bacteriophage fX174. J. Virol. 88:5042-5049.
    47. Combe M., Sanjuán R. (2013). Variation in RNA virus mutation rates across host cells. PLoS Pathog. 10: e1003855.
    48. Bradwell K., Combe M., Domingo-Calap P., Sanjuán R. (2013). Correlation between mutation rate and genome size in riboviruses: mutation rate of bacteriophage QβGenetics 195: 243-251.
    49. Sanjuán R., Nebot M.R., Peris J.B., Alcamí J. (2013). Immune activation promotes evolutionary conservation of T-cell epitopes in HIV-1. PLoS Biol. 11: e1001523.
    50. Pereira-Gómez M., Peris J.B., Sanjuán R. (2013). Seguint la pista del VIH: els estudis evolutius i la comprensió de la SIDA. Mètode 78: 61- 67.
    51. Furió V., Garijo R., Durán M., Moya A., Bell J.C., Sanjuán R. (2012). Relationship between within-host fitness and virulence in the vesicular stomatitis virus: correlation with partial decoupling. J. Virol. 86: 12228-36
    52. Vale P.F., Choisy M., Froissart R., Sanjuán R., Gandon S. (2012). The distribution of mutational fitness effects of phage fX174 on different hosts. Evolution 66: 3495-507.
    53. Domingo-Calap P., Pereira-Gómez M., Sanjuán R. (2012). Nucleoside analogue mutagenesis of a single-stranded DNA virus: evolution and resistance. J. Virol. 86: 9640-9646.
    54. Sanjuán R. (2012). From molecular genetics to phylodynamics: evolutionary relevance of mutation rates across viruses. PLoS Pathog. 8:e1002685.
    55. Manrubia S., Sanjuán R. (2012). Shape matters: effect of point mutations on RNA secondary structure. Advances in Complex Systems 13: 25.
    56. Sanjuán R., Lázaro E., Vignuzzi M. (2012). Biomedical implications of viral mutation and evolution. Future Virol. 7: 1-12.
    57. Cuevas J.M., Domingo-Calap P., Sanjuán R. (2012). The fitness effects of synonymous mutations in DNA and RNA viruses. Mol. Biol. Evol. 29: 17-20.
    58. Belshaw R., Sanjuán R., Pybus O.G. (2011). Viral mutation and substitution: units and levels. Curr. Opin. Virol. 1: 430-435.
    59. Cuevas J.M., Pereira-Gómez M., Sanjuán R. (2011). Mutation rate of bacteriophage ϕX174 modified through changes in GATC sequence context. Infect. Genet. Evol. 11:1820-1822.
    60.  Domingo-Calap P., Sanjuán R. (2011). Experimental evolution of RNA versus DNA viruses. Evolution 65: 2987-2994
    61. Sanjuán R., Domingo-Calap P. (2011). Experimental evolution in viruses. Encyclopedia of Life Sciences.  DOI: 10.1002/9780470015902.a0022857.
    62. Sanjuán R., Bordería A.V. (2011). Interplay between RNA structure and protein evolution in HIV-1. Mol. Biol. Evol. 28: 1333-1338.
    63. Sanjuán R., Nebot M.R., Chirico N., Mansky L.M., Belshaw R. (2010). Viral mutation rates. J. Virol. 84: 9733-9748 .
    64. Domingo-Calap P., Pereira-Gómez M., Sanjuán R. (2010). Selection for thermostability can lead to the emergence of mutational robustness in an RNA virus. J. Evol. Biol. 23: 2453-2460 .
    65. Sanjuán R., Bradwell K. (2010). Book review: The Evolution and Emergence of RNA viruses (Author: E.C. Holmes). Syst. Biol. 59: 610-612.
    66. Cuevas J.M., Sanjuán R., Moya A. Evolución experimental en virus (2010) in: Adaptación y Evolución (Eds: H. Dopazo, A. Navarro), p. 439-446. Obrapropia.
    67. González-Candelas F., Sanjuán R. The population genetics of human viral pathogens (2010) in: Microbial Population Genetics (Ed: Jianping Xu) p. 167-188.
    68. Sanjuán R. (2010). Mutational fitness effects in RNA and single-stranded DNA viruses: common patterns revealed by site-directed mutagenesis studies. Philos. Trans. Roy. Soc. Lond. B 365: 1975-1982 .
    69. Peris J.B., Davis P., Cuevas J.M., Nebot M.R., Sanjuán R. (2010). Distribution of fitness effects caused by single-nucleotide substitutions in bacteriophage f1. Genetics 185: 603-609.
    70. Domingo-Calap P., Cuevas J.M., Sanjuán R. (2009). The fitness effects of random mutations in single-stranded DNA and RNA bacteriophages. PLoS Genet. 5: e1000742 .
    71. Cuevas J.M., Duffy S., Sanjuán R. (2009). Point muation rate of bacteriophage fX174. Genetics 183: 747-749 .
    72. Cuevas J.M., Moya A., Sanjuán R. (2009). A genetic background with low mutational robustness is associated with increased adaptability to a novel host in an RNA virus. J. Evol. Biol. 22: 2041-2048 .
    73. Domingo-Calap P., Sentandreu V., Bracho A., González-Candelas F., Moya A., Sanjuán R. (2009). Unequal distribution of RT-PCR artifacts along the E1-E2 region of hepatitis C virus. J. Virol. Methods 161: 136-140.
    74. Cuevas J.M., Domingo-Calap P., Pereira-Gómez M., Sanjuán R. (2009). Experimental evolution and population genetics of RNA viruses.  The Open Evolution Journal 3: 9-16.
    75. Cuevas J.M., González-Candelas F., Moya A., Sanjuán R. (2009), Effect of ribavirin on the mutation rate and spectrum of hepatitis C virus in vivo. J. Virol. 83: 5760-5764.
    76. Cuevas J.M., Sanjuán R. (2009). Evolución experimental: evolución en tiempo real. Apuntes de Ciencia y Tecnología 30: 30-34.
    77. Sanjuán R., Agudelo-Romero P., Elena S.F. (2009). Upper-limit mutation rate estimation for a plant virus. Biol. Lett. 5: 394-396.
    78. Gago S., Elena S.F., Flores R., Sanjuán R. (2009). Extremely high mutation rate of a hammerhead viroid. Science 323: 1308.
    79. Elena S.F., Sanjuán R. (2008) The effect of genetic robustness on evolvability in digital organisms. BMC Evol. Biol. 8: 284.
    80. Clune J., Misevic D., Ofria C., Lenski R., Elena S.F., Sanjuán R. (2008). Selection fails to optimize mutation rates in rugged fitness landscapes. PLoS Comput. Biol. 4: e1000187 .
    81. Carrillo F.Y., Sanjuán R., Moya A., Cuevas J.M. (2008). Enhanced adaptation of vesicular stomatitis virus in cells infected with vaccinia virus. Infect. Genet. Evol. 8: 614-620.
    82. Sanjuán R., Nebot M.R. (2008) A network model for the correlation between epistasis and genomic complexity. PLoS ONE 3: e2663.
    83. Bull J.J., Sanjuán R., and Wilke C.O. Lethal mutagenesis (2008) in: Origin and Evolution of Viruses (Eds: E. Domingo, C. Parrish, J. Holland), p. 207-218.
    84. Sanjuán R. Quasispecies and experimental evolution of RNA viruses (2008) in: Enciclopedia of Virology (Eds: B.W.J. Mahy, M.H.V. Van Regenmortel), p. 359-365.
    85. Elena S.F., Agudelo-Romero P., Carrasco P., Codoñer F.M., Martín S., Torres C., and Sanjuán R. (2008). Experimental evolution of plant RNA viruses. Heredity 100: 478-483.
    86. Serrani J.C., Sanjuán R., Fos M., García-Martínez J.L. (2007). Gibberellin regulation of fruit-set and growth in tomato. Plant Physiol. 145: 246-257 .
    87. Elena S.F. and Sanjuán R. (2007). Virus evolution: insights from an experimental approach. Annu. Rev. Ecol. Evol. Syst. 38: 27-52 .
    88. Sanjuán R. and Daròs J.A. (2007). Site-directed mutagenesis of viroid dimeric cDNA. J. Virol. Methods 145: 71-75.
    89. Sanjuán R., Cuevas J.M., Furió V., Holmes E.C., and Moya A. (2007). Selection for robustness in mutagenized RNA viruses. PLOS Genet. 15: e93.
    90. Bordería A.V., Codoñer F.M., and Sanjuán R. (2007) Selection promotes organ compartmentalization in HIV-1: evidence form gag and pol genes. Evolution 61: 272-279.
    91. Bull J.J., Sanjuán R., and Wilke C.O. (2007) Theory of lethal mutagenesis for viruses. J. Virol. 81: 2930-2939 .
    92. Furió V., Moya A., and Sanjuán R. (2007). The cost of replication fidelity in human immunodeficiency virus type 1. Proc. Biol. Sci. 274: 225-230.
    93. Carrillo F.Y., Sanjuán R., Moya A., and Cuevas F.M. (2007). The effect of co- and superinfection on the adaptive dynamics of vesicular stomatitis virus. Infect. Genet. Evol. 7: 69-73.
    94. Czarna A., Sanjuán R., González-Candelas F., and Wróbel B. (2006). Topology testing of phylogenies using least squares methods. BMC Evol. Biol., 6: 105.
    95. Sanjuán R. and Elena S.F. (2006). Epistasis correlates to genomic complexity. Proc. Natl. Acad. Sci. USA 103: 14402-14405.
    96. Sanjuán R., Forment J., and Elena S.F. (2006). In silico predicted robustness of viroids RNA secondary structures. II. Interaction between mutation pairs. Mol. Biol. Evol. 23: 2123-2130.
    97.  Sanjuán R., Forment J., and Elena S.F. (2006). In silico predicted robustness of viroids RNA secondary structures. I. The effect of single mutations. Mol. Biol. Evol. 23: 1427-1436.
    98. Sanjuán R. (2006) Quantifying antagonistic epistasis in a multifunctional RNA secondary structure of the Rous sarcoma virus. J. Gen. Virol., 87: 1595-1602 .
    99. Elena SF., Carrasco P., Daròs J.A., and Sanjuán R. (2006). Mechanisms of genetic robustness in RNA viruses. EMBO R. 7: 168-173.
    100. Furió V., Moya A., and Sanjuán R. (2005). The cost of replication fidelity in an RNA virus. Proc. Natl. Acad. Sci. USA 102: 10233-10237.
    101. Elena S.F. and Sanjuán R. (2005). On the adaptive value of high mutation rates in RNA viruses: separating causes from consequences. J. Virol., 79, 11555-11558.
    102. Sanjuán R., Cuevas J.M., Moya A., and Elena S.F. (2005). Epistasis and the adaptability of an RNA virus. Genetics 170: 1001-1008.
    103. Elena S.F. and Sanjuán R. (2005). RNA viruses as complex adaptive systems. Biosystems 81: 31-41.
    104. Sanjuán R. and Wróbel B. (2005). Weighted least-squares likelihood ratio test for branch testing in phylogenies reconstructed from distance methods. Syst. Biol., 54: 218-229.
    105. Cuevas J.M., Sanjuán R., Moya A., and Elena S.F. (2005). Mode of selection and experimental evolution of antiviral drugs resistance in vesicular stomatitis virus. Infect. Genet. Evol. 5: 55-65.
    106. Cuevas J.M., Moya A., and Sanjuán R. (2005). Following the very initial growth of biological RNA viral clones. J Gen. Virol. 86: 435-443.
    107. Sanjuán R., Moya A., and Elena S.F. (2004). The contribution of epistasis to the architecture of fitness in an RNA virus. Proc. Natl. Acad. Sci. USA 101: 15376-15379 .
    108. Sanjuán R., Moya A., and Elena S.F. (2004). The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus. Proc. Natl. Acad. Sci. USA 101: 8396-8401.
    109. Sanjuán R., Codoner F.M., Moya A., and Elena S.F. (2004). Natural selection and the organ-specific differentiation of HIV-1 V3 hypervariable region. Evolution 58: 1185-1194.
    110. Elena S.F. and Sanjuán R. (2003). Evolution: Climb every mountain? Science 302: 2074-2075.
    111. Elena S.F., Codoñer F.M., Cuevas J.M., and Sanjuán R. (2003). Adaptive dynamics during experimental evolution of RNA viruses. Biology International 44: 75-78.
    112. Elena S.F., Codoñer F.M., and Sanjuán R. (2003). Intraclonal variation in RNA viruses: generation, maintenance and consequences. Biol. J. Linn. Soc. 79: 17-26.
    113. Elena S.F., Sanjuán R., Borderia A.V., and Turner P.E. (2002). Differential effects of horizontal and vertical transmission in the fitness of an RNA virus: A reanalysis. Infect. Genet. Evol. 1: 307-309.
    114. Sanjuán R. and Marín I. (2001). Tracing the origin of the compensasome: evolutionary history of DEAH helicase and MYST acetyltransferase gene families. Mol. Biol Evol. 18: 330-343. 


Universitat de Valè
ncia, 2020