Model systems

Viruses are excellent model systems for studying evolution because they evolve fast under lab conditions, which allows us to do 'real time' analyses. Moreover, their small genomes facilitate genetic manipulation and the study of the genetic bases of adaptation. We have worked both at the computational and experimental levels with several viruses:

Bacteriophages. RNA (Qbeta, MS2, SP) and single-stranded DNA (phiX174, G4, f1/m13) coliphages, all of which infect the same host strain, thus allowing us to perform direct comparisons between viral species.

Vesicular stomatitis virus (VSV), a negative-stranded RNA virus belonging to the family Rhabdoviridae. As most RNA viruses, it has a small genome size (11 kb), a high per-base mutation rate (~10^-4-10^-5), and low tolerance to mutations (~40% random nucleotide substitutions are lethal to the virus). In the wild, it is of particular importance to farmers in regions where it can infect livestock. In the lab, it has been extensively used for experimental evolution.

Transmissible gastroenteritis virus (TGEV), a model coronavirus. Using samples kindly provided by Prof. Luis Enjuanes (CSIC, Madrid), we are measuring the mutation rate of this virus. Coronaviruses are probably the only RNA viruses whose polymerases are able of proofreading, and this should result in relatively low mutation rates.

Hepatitis C virus (HCV) constitutes a major global health concern. We have analyzed sequence datasets in collaboration with Prof. Fernando González-Candelas to investigate the effect of the interferon-ribavirin therapy on the viral mutation rate.

HIV-1. Given the huge amount of information available for this virus, it constitutes an excellent model for studying evolution at the molecular level. For instance, in collaboration with Dr. Antonio V. Borderia (Institut Pasteur), we have shown that HIV-1 evolution is constrained by selection operating simultaneously at the RNA structure and protein levels. We are also investigating how immune pressure shapes HIV-1 sequence variability.

Viroids are plant infectious agents constituted by a minimal (200-400 nt) RNA genome that does not code for any protein. In collaboration with the groups of the Profs. Santiago F. Elena and Ricardo Flores, we have performed several in silico analyses of their RNA secondary structure and have measured the per-base mutation rate of a hammerhead viroid, which turned out to be the highest described for any biological entity.