Research Project in collaboration between: ICREA/Complex Systems Lab, Universitat Pompeu Fabra Plant Virus Diversity and Evolution Group, CSIC Valencia Main Researchers : Ricard V. Solé, Santiago Elena Josep Sardanyes Sergi Valverde Viruses and viroids are the simpler forms of replicating structures inhabiting our biosphere. They are known as the most important intracellular parasites, using genetic information from their hosts in order to replicate themselves. They can only reproduce by invading and controlling other cells as they lack the cellular machinery for self-reproduction. The term virus usually refers to those particles that infect eukaryotes, whilst the term bacteriophage or phage is used to describe those infecting prokaryotes. Figure : both RNA (left, polio) and DNA (right, herpes) viruses are intracellular parasites inhabiting the edge between the living and the non-living. The pictures have been taken from the The Big Picture Book of Viruses website. Our joint research wishes to understand, from both theoretical and experimental perspectives, the origins of complexity and plasticity of viruses, particularly focusing on RNA viruses. To this goal, we are using well-defined experimental systems (mainly viroids infecting plants) together mathematical and computer models looking for understanding of how viruses explore their worlds. Among other questions, we want to know how viruses and their hosts co-evolve, what is the structure of their fitness landscapes, how they cope with their complexity and how they might have originated and perhaps, canalized the evolution of biological complexity.

NEWS 1/1/2007    Launching the VIRUS DYNAMICS SITE 2007    Last paper: Information catastrophe in RNA viruses through replication thresholds, by: Ricard V. Solé, Josep Sardanyés, Juana Díez and Antonio Mas. J. Theor. Biol. 2006

Thresholds to RNA virus stability RNA viruses are known to replicate at very high mutation rates. These rates are actually known to be close to their so-called error threshold. This threshold is in fact a critical point beyond which genetic information is lost through a so called error catastrophe . However, the transition from a stable quasispecies to genetic drift and loss of information can also occur by crossing replication thresholds: below some replication rates, the viral population gets suddenly unable to survive. Available data from hepatitis C virus population analysis (see A. Mas et al., J. Gen. Virol. vol 85 (2004) pp. 3619-3626) can be interpreted through this theoretical view, providing evidence for such a replication threshold. Left: hepatitis C virus. Right: the two phases of a simple quasispecies model In its simplest form, we can consider a reduced system of equations defining a population as formed by two basic groups: the master sequence x1 and the other sequences, which we assume to be grouped into an "average" sequence with population x2 (Swetina and Schuster, 1982). Let us also assume (as a first approximation) that mutations occur from the master to the second compartment but not in the reverse sense. The enormous size of the sequence space makes this assumption a good first approximation. The model is given by the next two ordinary differential equations set: It can be shown that the stability condition for the master sequence to persist is given by the inequality: In the previous figure (right) we show the two possible phases, separated by the critical line, using a fixed f2 value (here f_2=0.25). Once such boundary is crossed, we shift from one type of qualitative dynamics to the other. The standard error threshold condition is associated to an increase in mutation rate. Increased mutation rates crossing the critical line drive the master sequence into extinction. But another possibility becomes obvious by considering the second parameter: as the master sequence replication rate decreases, we can also perform the same type of phase transition. Such scenario is consistent with a successful immune response against the dominant sequence, which leads to a decreased viability of the master sequence. This actually explains several key features of the observed quasispecies complexity observed in the HCV infected patients.

FITNESS LANDSCAPES AND VIRAL EVOLUTION Viral evolution takes place on fitness landscapes. The structure of such landscapes is one of the key topics to be explored by our Lab and collaborating teams. How the neutrality and rugeddness of landscapes affects and is affected by viral dynamics will be explored using different theoretical approaches. See our related papers: Climb every mountain? Elena, S.F. and Sanjuán, R. (2003). Science 302: 2074-2075. Evolution experiments with microorganisms: the dynamics and genetic bases of adaptation. Elena, S.F. and Lenski, R.E. (2003). Nature Rev. Genetics 4: 457-469.   VIRUS AND DIGITAL EVOLUTION RELATED WEBSITES Big Picture Book of Viruses The Big Picture Book of Viruses is intended to serve as both a catalog of virus pictures on the Internet and as an educational resource to those seeking more information about viruses. To this end, it is intimately linked to All the Virology on the WWW, and our collection of Virology Courses and Tutorials. There are several ways to access the information in the Big Picture Book of Viruses. All viruses are listed according to the family to which they have been assigned by the International Committee on Taxonomy of Viruses (ICTV). The images and other data can be obtained by the routes listed. All the Virology in the WWW All the Virology on the WWW seeks to be the best single site for Virology information on the Internet. We have collected all the virology related Web sites that might be of interest to our fellow virologists, and others interested in learning more about viruses. Additionally, we have created an index to virus pictures on the web, The Big Picture Book of Viruses, which also functions as a resource for viral taxonomy. A collection of some of the best Online Virology and Microbiology Course Notes available can also be found here. If you're interested in even more information, we have The Virology Bookshop, an on-line microbiology and virology bookstore with a significant discount for our users. Evolutionary Biology and Biocomplexity: Chris Adami's Lab We study fundamental properties of the evolutionary process, using theoretical and computational methods. Evolutionary theory has a claim of universality, in the sense that the theory does not make any reference to its instantiation, that is, how information is encoded. We therefore often use populations of self-replicating computer programs (also known as digital life) to perform simple evolutionary experiments. We believe that evolutionary theory can be treated just like any theory in physics, where theories inspire experiments, who in turn can be designed to validate of falsify theories. Digital virus evolution: Claus Wilke RNA viruses (such as influenza virus, human immunodeficiency virus, or hepatitis A, B, C virus) tend to have very high mutation rates. As a consequence, they can evolve rapidly in reaction to immune response or treatment. Frequently, they adapt to new hosts, and the majority of newly emerging infectious diseases are RNA viruses that cross the species barrier from animal host to human (examples are SARS or the avian influenza). However, a high mutation rate also implies frequent deleterious mutations. I am studying questions such as how RNA viruses can thrive under high rates of deleterious mutations, how they can mask the effect of deleterious mutations under coinfection, and how they adapt to changing hosts. In silico and in vitro microbial evolution: Lenski's Lab The main focus of my lab is on experimental evolution. Evolution is usually investigated using the comparative method or by studying fossils. Our approach is to watch evolution as it happens, in the context of experiments that are replicated and performed under controlled conditions. The idea of watching evolution in action is not new. In fact, Charles Darwin, in the first edition of On the Origin of Species (1859, p. 187), said In looking for the gradations by which an organ in any species has been perfected, we ought to look exclusively to its lineal ancestors ; but this is scarcely ever possible, and we are forced in each case to look to species of the same group, that is to the collateral descendants from the same original parent-form. In order to study evolution as it happens we are now performing experiments with two different fast-evolving systems: (a) Bacteria, primarily Escherichia coli; and (b) Digital organisms in the Avida system.