Evolutionary Systems Virology Group

Dynamical Systems and Computational Virology CSIC-Centre de Reçerca Matemàtica Associated Unit

Prof. Santiago F. Elena

CSIC Professor

SFI External Professor

IPP-CAAS Adjunct Professor

Instituto de Biología Integrativa de Sistemas

MSc in Biochemistry, Universitat de València, 1990
Ph.D. in Molecular and Evolutionary Genetics,
Universitat de València, 1995

Research Interests:

In general, my scientific interests are related with the evolutionary biology of microbes.  More concretely, this interest is focused in the study, within the framework of Populations Genetics, of the mechanisms that generate and maintain the genetic variability of RNA viruses.  The model systems that we use now for our experiments are the RNA viruses Tobacco etch potyvirus (TEV) and Turnip mosaic potyvirus (TuMV), the para-retrovirus Cauliflower mosaic caulimovirus (CaMV), and the viroids.  I have also been exploring the endless potential of digital organisms as model systems for evolutionary studies.  And finally, to avoid missing the wave of Systems Biology we are now developing in silico and mathematical hierarchical models of the entire viral infectious cycle.


Among the projects that we are currently working on, I would like to highlight the following:

  1. Role of Arabidopsis thaliana's genetic diversity for susceptibility-to-infection genes and resistance signaling pathways in the evolution of virulence of a picorna-like plant virus, turnip mosaic potyvirus (TuMV).
  2. Interplay between epigenetic modifications and viral infection. In collaboration with Prof. Sir David Baulcombe (University of Cambridge, Cambridge, UK) and Dr. Gustavo G. Gómez (I2SysBio).
  3. Role of epigenetics in the synergistic/antagonistic interactions among viruses coinfecting the same A. thaliana plant.
  4. Role of host's population structure and local adaptation in the rates of TuMV evolution and the evolution of its virulence and infectivity.
  5. Using genome-wide association studies (GWAS) to identify A. thaliana genes differentially responding to  infection with non-adapted and well-adapted TuMV strains.  In collaboration with Prof. Magnus Nordborg (Gregor Mendel Institute, Vienna, Austria).
  6. Using GWAS to identify host genes that are differentially targeted by generalist and specialist TuMV strains.
  7. Experimental determination and computational analysis of host-potyvirus protein-protein interaction networks (PPIN) and their evolution. In collaboration with Dr. Guillermo Rodrigo (I2SysBio) and Dr. Sergi Valverde (CSIC-Institut de Biologia Evolutiva, Barcelona, Spain).
  8. Evolutionary transitions from parasitism to mutualism in plant-virus pathosystems as a response to environmental stresses. In collaboration with Prof. Pedro Carrasco (Universitat de València, València, Spain) and Prof. Aurelio Gómez-Cadenas (Universitat Jaume I, Castelló, Spain).
  9. Evolution of mechanisms of genetic robustness in highly mutable RNA genomes. Test of the plastogenetic congruence hypothesis for the evolution of mutational robustness.
  10. Evolution of genetic architecture, gene content and gene order in picorna-like plant potyviruses.
  11. Molecular evolution, phylogenetics, phylogeography and molecular epidemiology studies of different plant (e.g., apple stem pitting foveavirus, pepino mosaic potexvirus, potato Y potyvirus, tomato black ring nepovirus, tospoviruses...) and fungal (Thrichoderma harziaunum bipartite mycovirus 1) viruses. In collaboration with a wide network of awesome colleagues abroad.
  12. Identification of early-warning signals of transitions from health to disease during plant infections using transcriptomic data. Development of new statistical and computational approaches. In collaboration with Dr. José A. OteoDr. Wladimiro Díaz and Dr. Vicente Arnau (I2SysBio).
  13. Development of mathematical models of virus-host coevolution in fluctuating coupled fitness landscapes. In collaboration with Prof. Ricard V. Solé (ICREA-Universitat Pompeu Fabra, Barcelona, Spain) and Dr. Sergi Valverde.
  14. Development of mathematical models for the evolution of specialist and generalist viruses. In collaboration with Dr. Josep Sardanyés and Prof. Lluís Alsedà (Centre de Recerca Matemàtica, Barcelona, Spain).
  15. Mathematical models for the evolution of segmented multipartite viruses, RNA satellites and defective interfering particles. In collaboration with Dr. Josep Sardanyés and Dr. Tomás Alarcón (Centre de Recerca Matemàtica, Barcelona, Spain),  Dr. J. Tomás Lázaro (Universitat Politècnica de Catalunya, Barcelona, Spain) and Dr. Mark P. Zwart (KNAW-NIOO, Wageningen, The Neatherlands).
  16. Mathematical and simulation models to understand the origin and evolution of viroids and other small non-coding infectious RNAs. In collaboration with Dr. Susanna Manrubia (CSIC-Centro Nacional de Biotecnología, Madrid, Spain) and Dr. José A. Cuesta (Universidad Carlos III, Madrid, Spain).
  17. Mathematical and simulation models for exploring the rules of microbiome assambly: from Black Queen to Red Queen. In colaboration with Prof. David Wolpert and Dr. Jacopo Grilli (Santa Fe Institute, Santa Fe NM, USA).


Selected Publications:

  • Elena, S.F., Dopazo, J., Diener, T.O., Flores, R., and Moya, A. (1991). Phylogeny of viroids, viroid-like satellite RNAs ant the viroid-like domain of Human Hepatitis Delta Virus. Proc. Natl. Acad. Sci. USA 88: 5631-5634.
  • Clarke, D.K., Duarte, E.A., Elena, S.F., Moya, A., Domingo, E., and Holland, J.J. (1994). The Red Queen reigns in the kingdom of RNA viruses. Proc. Natl. Acad. Sci. USA 91: 4821-4824.
  • Novella, I.S., Duarte, E.A., Elena, S.F., Moya, A., Domingo, E., and Holland, J.J. (1995). Exponential increases of RNA virus fitness during repeated transmission. Proc. Natl. Acad. Sci. USA 92: 5841-5844.
  • Elena, S.F., Cooper, V.S., and Lenski, R.E. (1996). Punctuated evolution caused by selection of rare beneficial mutations. Science 272: 1802-1804.
  • Elena, S.F., Cooper, V.S., and Lenski, R.E. (1996). Mechanisms of punctuated evolution? Reply. Science 274: 1749-1750.
  • Elena, S.F. and Lenski, R.E. (1997). Test of Synergistic Interactions between deleterious mutations in bacteria. Nature 390: 395-398.
  • Miralles, R., Gerrish, P.J., Moya, A., and Elena, S.F. (1999). Clonal interference and the evolution of RNA viruses. Science 285: 1745-1747.
  • Moya, A., Elena, S.F., Bracho, A., Miralles, R., and Barrio, E. (2000). The evolution of RNA viruses: a population genetic view. Proc. Natl. Acad. Sci. USA 97: 6967-6973.
  • Fares, M.A., Ruiz-González, M.X., Moya, A., Elena, S.F., and Barrio, E. (2002). Endosymbiotic bacteria: GroEL buffers against deleterious mutations. Nature 417: 398.
  • Elena, S.F. and Lenski, R.E. (2003). Evolution experiments with microorganisms: the dynamics and genetic bases of adaptation. Nat. Rev. Genet. 4: 457-469.
  • Elena, S.F. and Sanjuán, R. (2003). Climb every mountain? Science 302: 2074-2075.
  • 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.
  • 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.
  • Sanjuán, R. and Elena, S.F. (2006). Epistasis correlates to genomic complexity. Proc. Natl. Acad. Sci. USA 103: 14402-14405.
  •  de Visser, J.A.G.M. and Elena, S.F. (2007). The evolution of sex: empirical insights into the roles of epistasis and drift. Nat. Rev. Genet. 8: 139-149.
  • Martin, G., Elena, S.F. and Lenormand, T. (2007). Distribution of epistasis in microbes fit predictions from a fitness landscape model. Nat. Genet. 33: 555-560.
  • Elena, S.F. and Sanjuán, R. (2007). Virus evolution: insights from an experimental approach. Annu. Rev. Ecol. Evol. Syst. 38: 27-52.
  • Gago, S., Elena, S.F., Flores, R. and Sanjuán, R. (2009). Extremely high mutation rate of a hammerhead viroid. Science 323: 1308.
  • Carrera, J., Elena, S.F. and Jaramillo, A. (2012). Computational design of genomic transcriptional networks with adaptation to varying environments. Proc. Natl. Acad. Sci. USA 109: 15277-15282.
  • Flores, R., Gago-Zachert, S., Serra, P., Sanjuán, R. and Elena, S.F. (2014). Viroids: survivors from RNA world? Annu. Rev. Microbiol. 68: 395-414.
  • Zwart, M.P., Elena, S.F. (2015). Matters of size: genetic bottlenecks in virus infection and their potential impact on evolution. Annu. Rev. Virol. 2: 161-179.
  • Lefeuvre, P., Martin, D., Elena, S.F., Shepherd, D.N., Roumagnac, P., Varsani, A. (2019). Evolution and ecology of plant viruses. Nat. Rev. Microbiol. 17: 632-644.
  • Gonzalez, R., Butkovi?, A., Escaray, F.J., Martínez-Latorre, J., Melero, I., Pérez-Parets, E., Gómez-Cadenas, A., Carrasco, P., Elena, S.F. (2021). Plant virus evolution under strong drought conditions results in a transition from parasitims to mutualism. Proc. Natl. Acad. Sci. USA. 118: e2020990118.


And the most recently published…

  • Mongelli, V., Lequime, S., Lousathanas, A., Gausson, V., Blanc, H., Nigg, J., Quintana-Murci, L., Elena, S.F., Saleh, M.C. (2022). Innate immune pathways act synergistically to constrain RNA virus evolution in Drosophila melanogaster. Nat. Ecol. Evol. 6: 565-578.

At the present, I'm Editorial Advisor for BMC Evol Biol
and co-editor in chief for



I was elected EMBO Member in 2011.
And member of the American Academy of Arts and Sciences in 2020


I’m also an external professor at The Santa Fe Institute (New Mexico, USA), a great place for doing multidisciplinary science.


I'm also Adjunct Professor at the Chinese Academy of Agricultural Sciences Institute of Plant Protection


Follow this link for a complete description of my CV.

Contact Information:

Prof. Santiago F. Elena

Instituto de Biología Integrativa de Sistemas (CSIC-UV)

Parc Cientific UV

CL. Catedrático Agustín Escardino 9, Paterna

46980 València



Phone: +34 963 544 779



           Last modified: February 29th, 2022

Go to the lab webpage
Go to the
I2SysBio main homepage
Go to the CSIC main homepage
Go to the
Universitat de València main homepage
Go the Santa Fe Institute homepage