Stability of a stochastically perturbed model of intracellular single-stranded RNA virus replication

Replication of single-stranded RNA virus can be complicated, compared to that of double-stranded virus, as it require production of intermediate antigenomic strands that then serve as template for the genomic-sense strands. Moreover, for ssRNA viruses, there is a variability of the molecular mechanism by which genomic strands can be replicated. A combination of such mechanisms can also occur: a fraction of the produced progeny may result from a stamping-machine type of replication that uses the parental genome as template, whereas others may result from the replication of progeny genomes. F. Mart\'{\i}nez et al. and J. Sardany\'{e}s at al. suggested a deterministic ssRNA virus intracellular replication model that allows for the variability in the replication mechanisms. To explore how stochasticity can affect this model principal properties, in this paper we consider the stability of a stochastically perturbed model of ssRNA virus replication within a cell. Using the direct Lyapunov method, we found sufficient conditions for the stability in probability of equilibrium states for this model. This result confirms that this heterogeneous model of single-stranded RNA virus replication is stable with respect to stochastic perturbations of the environment

Quasispecies Spatial Models for RNA Viruses with Different Replication Modes and Infection Strategies

Empirical observations and theoretical studies suggest that viruses may use different replication strategies to amplify their genomes, which impact the dynamics of mutation accumulation in viral populations and therefore, their fitness and virulence. Similarly, during natural infections, viruses replicate and infect cells that are rarely in suspension but spatially organized. Surprisingly, most quasispecies models of virus replication have ignored these two phenomena. In order to study these two viral characteristics, we have developed stochastic cellular automata models that simulate two different modes of replication (geometric vs stamping machine) for quasispecies replicating and spreading on a two-dimensional space. Furthermore, we explored these two replication models considering epistatic fitness landscapes (antagonistic vs synergistic) and different scenarios for cell-to-cell spread, one with free superinfection and another with superinfection inhibition. We found that the master sequences for populations replicating geometrically and with antagonistic fitness effects vanished at low critical mutation rates. By contrast, the highest critical mutation rate was observed for populations replicating geometrically but with a synergistic fitness landscape. Our simulations also showed that for stamping machine replication and antagonistic epistasis, a combination that appears to be common among plant viruses, populations further increased their robustness by inhibiting superinfection. We have also shown that the mode of replication strongly influenced the linkage between viral loci, which rapidly reached linkage equilibrium at increasing mutations for geometric replication. We also found that the strategy that minimized the time required to spread over the whole space was the stamping machine with antagonistic epistasis among mutations. Finally, our simulations revealed that the multiplicity of infection fluctuated but generically increased along time.This work has been funded by the Human Frontier Science Program Organization Grant RGP12/2008 and the Spanish Ministerio de Ciencia e Innovacio´n Grant BFU2009-06993. The authors also acknowledge support from the Santa Fe Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Magnitude and sign epistasis among deleterious mutations in a positive-sense plant RNA virus

How epistatic interactions between mutations determine the genetic architecture of fitness is of central importance in evolution. The study of epistasis is particularly interesting for RNA viruses because of their genomic compactness, lack of genetic redundancy, and apparent low complexity. Moreover, interactions between mutations in viral genomes determine traits such as resistance to antiviral drugs, virulence and host range. In this study we generated 53 Tobacco etch potyvirus genotypes carrying pairs of single-nucleotide substitutions and measured their separated and combined deleterious fitness effects. We found that up to 38% of pairs had significant epistasis for fitness, including both positive and negative deviations from the null hypothesis of multiplicative effects. Interestingly, the sign of epistasis was correlated with viral protein-protein interactions in a model network, being predominantly positive between linked pairs of proteins and negative between unlinked ones. Furthermore, 55% of significant interactions were cases of reciprocal sign epistasis (RSE), indicating that adaptive landscapes for RNA viruses maybe highly rugged. Finally, we found that the magnitude of epistasis correlated negatively with the average effect of mutations. Overall, our results are in good agreement to those previously reported for other viruses and further consolidate the view that positive epistasis is the norm for small and compact genomes that lack genetic robustness.Spanish Ministry of Science and Innovation BFU2009-06993 JAE program from CSICPeer reviewe

What Evolutionary Biologists Can Learn from Artificial Life

Big questions in Evolutionary Biology and experimental limitations - The evolution of complex traits. - The role of neutral variation in adaptive evolution. - Selection for fitness vs selection for robustness. - The topography of adaptive landscapes and the evolution of landscapes. - Eco-evolutionary dynamics: how evolution changes ecology and how ecology modulates evolution. - Evolution of phenotype-genotype maps. - The evolution of genetic systems (sex, speciation, genome architecture). The advantages of microbial Experimental Evolution - They are easy to propagate and enumerate. - They reproduce quickly, which allows experiments to run for many generations. - They allow large populations in small spaces, which facilitates experimental replication. -They can be stored in suspended animation and later revived, which allows the direct comparison of ancestral and evolved types. -Many microbes reproduce asexually and the resulting clonality enhances the precision of experimental replication. -Asexuality also maintains linkage between a genetic marker and the genomic background into which it is placed, which facilitates fitness measurements. -It is easy to manipulate environmental variables, such as resources, as well as the genetic composition of founding populations. - There are abundant molecular and genomic data for many species, as well as techniques for their precise genetic analysis and manipulation.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. BitLab (http://www.bitlab-es.com) Universidad de Málag

Robust dynamical pattern formation from a multifunctional minimal genetic circuit

<p>Abstract</p> <p>Background</p> <p>A practical problem during the analysis of natural networks is their complexity, thus the use of synthetic circuits would allow to unveil the natural mechanisms of operation. Autocatalytic gene regulatory networks play an important role in shaping the development of multicellular organisms, whereas oscillatory circuits are used to control gene expression under variable environments such as the light-dark cycle.</p> <p>Results</p> <p>We propose a new mechanism to generate developmental patterns and oscillations using a minimal number of genes. For this, we design a synthetic gene circuit with an antagonistic self-regulation to study the spatio-temporal control of protein expression. Here, we show that our minimal system can behave as a biological clock or memory, and it exhibites an inherent robustness due to a quorum sensing mechanism. We analyze this property by accounting for molecular noise in an heterogeneous population. We also show how the period of the oscillations is tunable by environmental signals, and we study the bifurcations of the system by constructing different phase diagrams.</p> <p>Conclusions</p> <p>As this minimal circuit is based on a single transcriptional unit, it provides a new mechanism based on post-translational interactions to generate targeted spatio-temporal behavior.</p

Different bat detectors and processing software… Same results?

There has been an increase in commercial bat detectors and noise filtering software for monitoring bat activity. In this study, we compare the recording efficiency of three bat detectors from the popular brand Wildlife Acoustics (Echo Meter 3, Echo Meter Touch Pro 1 and Song Meter 2 BAT) and the effectiveness of two noise filtering software (Kaleidoscope and SonoBat Batch Scrubber). To do so, we recorded 7513 files from 13 urban parks in Madrid in 2017, that were manually identified to species level. The results show that the Echo Meter 3 records significantly less activity than the Echo Meter Touch Pro 1 and Song Meter 2 BAT. Our results also identify SonoBat Batch Scrubber as more reliable than Kaleidoscope for preventing false negatives. Therefore, our study demonstrates that different bat detectors, and different noise filtering software, can provide different results

RNA virus genetic robustness: possible causes and some consequences

[EN] In general terms, robustness is the capacity of biological systems to function in spite of genetic or environmental perturbations. The small and compacted genomes and high mutation rates of RNA viruses, as well as the ever-changing environments wherein they replicate, create the conditions for robustness to be advantageous. In this review, I will enumerate possible mechanisms by which viral populations may acquire robustness, distinguishing between mechanisms that are inherent to virus replication and population dynamics and those that result from the interaction with host factors. Then, I will move to review some evidences that RNA virus populations are robust indeed. Finally, I will comment on the implications of robustness for virus evolvability, the emergence of new viruses and the efficiency of lethal mutagenesis as an antiviral strategyThis work was supported by the Spanish MICINN grant BFU2009-06993 and by the Santa Fe Institute. I thank Mark P. Zwart for critical reading of the manuscript.Elena Fito, SF. (2012). RNA virus genetic robustness: possible causes and some consequences. Current Opinion in Virology. 2(5):525-530. https://doi.org/10.1016/j.coviro.2012.06.008S5255302

Strategic assessment of transport infrastructure Plans on European integration. Application for the Spanish Strategic Transport and Infrastructure Plan 2005-2020

Traditional transport infrastructure assessment methodologies rarely include the full range of strategic benefits for the transportation system. One of these benefits is the contribution to cross-border integration. However, this is a key issue in strategic planning and decision-making processes, as its inclusion may increase the probability of large-scale transport infrastructure projects being funded. This paper presents a methodology for the measurement of the contribution of Transport Infrastructure Plans to cross-border integration. The methodology is based on the measurement of the improvement in network efficiency in cross-border regions of neighboring countries, via accessibility calculations in a Geographical Information System (GIS) support. The methodology was tested by applying it to the ambitious road and rail network extensions included in the Spanish Strategic Transport and Infrastructure Plan (PEIT) 2005-2020. The results show significant and important network efficiency improvements of the PEIT outside the Spanish border. For the road mode, while the Spanish average accessibility improvement accounts for 2.6%, average improvements in cross-border regions of France and Portugal are of 1.8%. And for the rail mode, the corresponding Spanish value is 34.5%, whereas in neighboring regions it accounts for 20.2%. These results stress the significant importance of this strategic benefit and the consequent need for its inclusion in strategic planning processes. Finally, the paper identifies the potential of the methodology when applied at different administrative levels, such as the local or state levels

The effect of genetic robustness on evolvability in digital organisms

<p>Abstract</p> <p>Background</p> <p>Recent work has revealed that many biological systems keep functioning in the face of mutations and therefore can be considered genetically robust. However, several issues related to robustness remain poorly understood, such as its implications for evolvability (the ability to produce adaptive evolutionary innovations).</p> <p>Results</p> <p>Here, we use the Avida digital evolution platform to explore the effects of genetic robustness on evolvability. First, we obtained digital organisms with varying levels of robustness by evolving them under combinations of mutation rates and population sizes previously shown to select for different levels of robustness. Then, we assessed the ability of these organisms to adapt to novel environments in a variety of experimental conditions. The data consistently support that, for simple environments, genetic robustness fosters long-term evolvability, whereas, in the short-term, robustness is not beneficial for evolvability but may even be a counterproductive trait. For more complex environments, however, results are less conclusive.</p> <p>Conclusion</p> <p>The finding that the effect of robustness on evolvability is time-dependent is compatible with previous results obtained using RNA folding algorithms and transcriptional regulation models. A likely scenario is that, in the short-term, genetic robustness hampers evolvability because it reduces the intensity of selection, but that, in the long-term, relaxed selection facilitates the accumulation of genetic diversity and thus, promotes evolutionary innovation.</p

Imagen de regia majestad: Carlos V y Felipe II en las Fuentes impresas de la Biblioteca Histórica “Marqués de Valdecilla”

Este artículo pretende profundizar, a través de las fuentes impresas presentes en la Biblioteca Histórica «Marqués de Valdecilla», en la concepción de la imagen regia que legaron a la posteridad Carlos V y Felipe II y en los vínculos de ambos monarcas con el mundo de las artes, prestando especial atención a la obra de Tiziano, a los viajes de juventud de Felipe II y a su Monasterio de San Lorenzo de El Escorial. [ABSTRACT]Based on printed sources preserved at Biblioteca Histórica «Marqués de Valdecilla», this paper focuses on analysing the conception of royal majesty which Charles V and Philip II pass on to posterity. Links of both monarchs to arts are also studied, giving special attention to Tiziano’s paintings, youth travels of Philip II and to his Monastery of El Escorial