Biology subjects

Elena, S.

Publications and source records attributed to Elena, S..

3 recordsLinked to original sources

bioRxiv2018

Noise-induced bistability in the quasineutral coexistence of viral RNA under different replication modes

Evolutionary and dynamical investigations on real viral populations indicate that RNA replication can range between two extremes given by so-called stamping machine replication (SMR) and geometric replication (GR). The impact of asymmetries in replication for single-stranded, (+) sense RNA viruses has been up to now studied with deterministic models. However, viral replication should be better described by including stochasticity, since the cell infection process is typically initiated with a very small number of RNA macromolecules, and thus largely influenced by intrinsic noise. Under appropriate conditions, deterministic theoretical descriptions of viral RNA replication predict a quasineutral coexistence scenario, with a line of fixed points involving different strands equilibrium ratios depending on the initial conditions. Recent research on the quasineutral coexistence in two competing populations reveals that stochastic fluctuations fundamentally alters the mean-field scenario, and one of the two species outcompetes the other one. In this manuscript we study this phenomenon for RNA viral replication modes by means of stochastic simulations and a diffusion approximation. Our results reveal that noise has a strong impact on the amplification of viral RNA, also causing the emergence of noise-induced bistability. We provide analytical criteria for the dominance of (+) sense strands depending on the initial populations on the line of equilibria, which are in agreement with direct stochastic simulation results. The biological implications of this noise-driven mechanism are discussed within the framework of the evolutionary dynamics of RNA viruses with different modes of replication.

systems biology↗

bioRxiv2017

Viral fitness predicts the magnitude and direction of perturbations in the infected host transcriptome

Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a mesoscopic property that captures into a single figure differences in performance at every stage of viral infection. But to which extent viral fitness results from particular molecular interactions with host factors and regulatory networks during infection? Can we identify host genes, and then functional classes, whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus (TEV) that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, that led to close fitness values, also resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with TEV fitness. Over-expression of genes with positive correlation activates hormone-and RNA silencing-mediated pathways of plant defense. By contrast, under-expression of genes negatively correlated reduces metabolism, growth, and development. Overall, these results reveal the high information content of viral fitness, and suggest its potential use to predict differences in genomic profiles of infected hosts.

evolutionary biology↗

bioRxiv2016

Non-linear tradeoffs allow cooperation to evolve from Prisoner’s Dilemma to Snow Drift

The existence of cooperation, or the production of public goods, is an evolutionary problem. Cooperation is not favored because the Prisoners Dilemma (PD) game drives cooperators to extinction. We have re-analyzed this problem by using RNA viruses to motivate a model for the evolution of cooperation. Gene products are the public goods and group size is the number of virions co-infecting the same host cell. Our results show that if the tradeoff between replication and production of gene products is linear, PD is observed. However, if the tradeoff is nonlinear, the viruses evolve into separate lineages of ultra-defectors and ultra-cooperators as group size is increased. The nonlinearity was justified by the existence of real viral ultra-defectors, known as defective interfering (DI) particles, which gain a nonlinear advantage by being smaller. The evolution of ultra-defectors and ultra-cooperators creates the Snow Drift game, which promotes high-level production of public goods.

evolutionary biology↗