bioRxiv Science⌕ Search

Biology subjects

Elena, S. F.

Publications and source records attributed to Elena, S. F..

48 records · Page 3Linked to original sources

Defects in plant immunity modulate the rates and patterns of RNA virus evolution

It is assumed that host genetic variability for susceptibility to infection necessarily conditions virus evolution. Differences in host susceptibility can either drive the virus to diversify into strains that track different defense alleles (e.g., antigenic diversity) or to infect only the most susceptible genotypes. To clarify these processes and their effect on virulence, we have studied how variability in host defense responses determine the evolutionary fate of viruses. To accomplish this, we performed evolution experiments with Turnip mosaic potyvirus in Arabidopsis thaliana mutants. Mutant plants had disruptions in infection-response signaling pathways or in genes whose products are essential for potyvirus infection. Genotypes were classified into five phenogroups according to their response to infection. In order to disentangle how host susceptibility affects virus adaptation, independent viral lineages were evolved in selected plant genotypes. Evaluating disease-related traits of the evolved lineages, we found that evolution proceeded faster in the most resistant hosts than in the most permissive ones, as expected for adaptation to a harsh environment. By sequencing the genomes of the evolved viral lineages, we found that the multifunctional protein VPg turned out to be the target of selection in most host genotypes. When all evolved viral lineages were tested for fitness in all plant genotypes used in the experiments, we found compelling evidences that generalist viruses were selected by the most restrictive plant genotypes, while permissive genotypes selected for specialist viruses. Overall, this work illustrates how different host defense signaling pathways constrain not only disease-related traits but virus evolution.

evolutionary biology↗

Increasing growth temperature alters the within-host competition of viral strains and influences virus genetic variation

The emergence of viral diseases in plant crops hamper the sustainability of food production, and this may be boosted by global warming. Concurrently, mixed viral infections are becoming common in plants, of which epidemiology are unpredictable due to within-host virus-virus interactions. However, the extent in which the combined effect of variations in the abiotic components of the plant ecological niche (e.g., temperature) and the prevalence of mixed infections (i.e., within-host interactions among viruses) affect the evolutionary dynamics of viral populations is not well understood. Here, we explore the interplay between ecological and evolutionary factors during viral infections, and show that two individual strains of pepino mosaic virus (PepMV) coexisted in a temperature-dependent continuum between neutral and antagonistic interactions in tomato plants. After a long-term infection, the mutational analysis of the evolved viral genomes revealed strain-specific single-nucleotide polymorphisms that were modulated by the interaction between the type of infection and temperature. Mathematical modeling allowed us to asses a thermal reaction norm for both strains, which indicated that viral replication rates were increased along with increasing temperature in mixed infections, with a remarkable strain-dependent effect. These results suggest that the growth temperature is an ecological driver of virus-virus interactions, with an effect on the genetic diversity of individual viruses co-infecting a host. This research provides insights into the effect that climate change will have on the evolutionary dynamics of viral populations.

evolutionary biology↗

Heterogeneity in the response of different subtypes of Drosophila melanogaster enteroendocrine cells to viral infections

Single cell RNA sequencing (scRNA-seq) offers the possibility to monitor both host and pathogens transcriptomes at the cellular level. Here, public scRNA-seq data from Drosophila melanogaster have been used to compare the differences in replication strategy and cellular response between two viruses, Thika virus (TV) and D. melanogaster Nora virus (DMelNV) in enteroendocrine cells (EEs). TV and DMelNV exhibited different patterns of replication and for TV, accumulation varied according to cell subtype. Cells infected with TV underwent down-regulation of genes that represent bottlenecks in the fruit fly interactome, while cells infected with DMelNV went through a down-expression of translation-related genes that represent both hubs and bottlenecks in the host interactome. In contrast, flies infected with DMelNV show only a systemic level down-regulation of bottleneck genes. Here, we use scRNA-seq to highlight the differences and commonalities between cellular response to TV and DMelNV and between cellular and systemic response to DMelNV.

systems biology↗

Revisiting Orthotospovirus Phylogeny Using Whole Genomic Data and a Hypothesis for their Geographic Origin and Diversification

The family Tospoviridae, a member of the Bunyavirales order, is constituted of tri-segmented negative-sense single-stranded RNA viruses that infect plants and are also able of replicating in their insect vectors in a persistent manner. The family is composed of a single genus, the Orthotospovirus, whose type species is Tomato spotted wilt virus (TSWV). Previous studies assessing the phylogenetic relationships within this genus were based upon partial genomic sequences, thus resulting in unresolved clades and a poor assessment of the roles of recombination and genome shuffling during mixed infections. Complete genomic data for most Orthotospovirus species are now available at NCBI genome database. In this study we have used 62 complete genomes from 20 species. Our study confirms the existence of four phylogroups (A to D), grouped in two major clades (A-B and C-D), within the genus. We have estimated the split between the two major clades [~]3,100 years ago shortly followed by the split between the A and B phylogroups [~]2,860 years ago. The split between the C and D phylogroups happened more recently, [~]1,465 years ago. Segment reassortment has been shown to be important in the generation of novel viruses. Likewise, within-segment recombination events have been involved in the origin of new viral species. Finally, phylogeographic analyses of representative viruses suggests the Australasian ecozone as the possible origin of the genus, followed by complex patterns of migration, with rapid global spread and numerous reintroduction events. IMPORTANCEMembers of the Orthotospovirus genus infect a large number of plant families, including food crops and ornamentals, resulting in multimillionaire economical losses. Despite this importance, phylogenetic relationships within the genus were established years ago based in partial genomic sequences. A peculiarity of orthotospoviruses is their tri-segmented negative sense genomes, which makes segment reassortment and within-segment recombination, two forms of viral sex, potential evolutionary forces. Using full genomes from all described orthotospovirus species, we revisited their phylogeny and confirmed the existence of four major phylogroups with uneven geographic distribution. We have also shown a pervasive role of sex in the origin of new viral species. Finally, using Bayesian phylogeographic methods, we assessed the possible geographic origin and historical dispersal of representative viruses from the different phylogroups.

evolutionary biology↗

Viral fitness determines the magnitude of transcriptomic and epigenomic reprogramming of defense responses in plants

Although epigenetic factors may influence the expression of defense genes in plants, their role in antiviral responses and the impact of viral adaptation and evolution in shaping these interactions are still poorly explored. We used two isolates of turnip mosaic potyvirus (TuMV) with varying degrees of adaptation to Arabidopsis thaliana to address these issues. One of the isolates was experimentally evolved in the plant and presented increased load and virulence relative to the ancestral isolate. The magnitude of the transcriptomic responses were larger for the evolved isolate and indicated a role of innate immunity systems triggered by molecular patterns and effectors in the infection process. Several transposable elements (TEs) located in different chromatin contexts and epigenetic-related genes were also affected. Correspondingly, mutant plants having loss or gain of repressive marks were, respectively, more tolerant and susceptible to TuMV, with a more efficient response against the ancestral isolate. In wild-type plants both isolates induced similar levels of cytosine methylation changes, including in and around TEs and stress-related genes. Results collectively suggested that apart from RNA silencing and basal immunity systems, DNA methylation and histone modification pathways may also be required for mounting proper antiviral defenses in plants and that the effectiveness of this type of regulation strongly depends on the degree of viral adaptation to the host.

evolutionary biology↗

Role of host genetic diversity for susceptibility-to-infection in the evolution of virulence of a plant virus

Predicting viral emergence is difficult due to the stochastic nature of the underlying processes and the many factors that govern pathogen evolution. Environmental factors affecting the host, the pathogen and the interaction between both are key in emergence. In particular, infectious disease dynamics are affected by spatiotemporal heterogeneity in their environments. A broad knowledge of these factors will allow better estimating where and when viral emergence is more likely to occur. Here we investigate how the population structure for susceptibility-to-infection genes of the plant Arabidopsis thaliana shapes the evolution of Turnip mosaic virus (TuMV). For doing so we have evolved TuMV lineages in two radically different host population structures: (i) multiple genetically homogeneous A. thaliana subpopulations and (ii) a single maximally genetically heterogeneous population. We found faster adaptation of TuMV to homogeneous than to heterogeneous host populations. However, viruses evolved in heterogeneous host populations were more pathogenic and infectious than viruses evolved in the homogeneous population. Furthermore, the viruses evolved in homogeneous populations showed stronger signatures of local specialization than viruses evolved in heterogeneous populations. These results illustrate how the genetic diversity of hosts in an experimental ecosystem favors the evolution of virulence of a pathogen.

evolutionary biology↗

Parsimonious scenario for the emergence of viroid-like replicons de novo

Viroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or several de novo independent evolutionary origins in plants. Here we discuss the plausibility of de novo emergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixed length, rod-like structures typical of Pospiviroidae are difficult to fix. Using different quantitative approaches, we evaluate the likelihood that RNA sequences fold into a rod-like structure and bear specific sequence motifs facilitating interactions with other molecules, e.g. RNA polymerases, RNases and ligases. By means of numerical simulations, we show that circular RNA replicons analogous to Pospiviroidae emerge if evolution is seeded with minimal circular RNAs that grow through the gradual addition of nucleotides. Further, these rod-like replicons often maintain their structure if independent functional modules are acquired that impose selective constraints. The evolutionary scenario we propose here is consistent with the structural and biochemical properties of viroids described to date.

evolutionary biology↗

Engineered Genetic Redundancy Relaxes Selective Constraints upon Endogenous Genes in Viral RNA Genomes

1Genetic redundancy, understood as the functional overlap of different genes, is a double-edge sword. At the one side, it is thought to serve as a robustness mechanism that buffers the deleterious effect of mutations hitting one of the redundant copies, thus resulting in pseudogenization. At the other side, it is considered as a source of genetic and functional innovation. In any case, genetically redundant genes are expected to show an acceleration in the rate of molecular evolution. Here we tackle the role of genetic redundancy in viral RNA genomes. To this end, we have evaluated the rates of compensatory evolution for deleterious mutations affecting an essential function, the suppression of RNA silencing plant defense, of tobacco etch potyvirus (TEV). TEV genotypes containing deleterious mutations in presence/absence of engineered genetic redundancy were evolved and the pattern of fitness and virulence recovery evaluated. Genetically redundant genotypes suffered less from the effect of deleterious mutations and showed relatively minor changes in fitness and virulence. By contrast, non-genetically redundant genotypes had very low fitness and virulence at the beginning of the evolution experiment that were fully recovered by the end. At the molecular level, the outcome depended on the combination of the actual mutations being compensated and the presence/absence of genetic redundancy. Reversions to wild-type alleles were the norm in the non-redundant genotypes while redundant ones either did not fix any mutation at all or showed a higher nonsynonymous mutational load.

evolutionary biology↗

Exploring the role of cellular homologous of the 30K-superfamily of plant virus movement proteins

Genes orthologous to the 30K-superfamily of movement proteins (MP) from plant viruses have been recently discovered by bioinformatics analyses as integrated elements in the genome of most vascular plants. However, their functional relevance for plants is still unclear. Here, we undertake some preliminary steps into the functional characterization of one of these putative MP genes found in Arabidopsis thaliana. We found that the AtMP gene is expressed at different stages of the plant development, with accumulation being highest in flowers but lowest in mature siliques. We also found down-regulation of the gene may result in a small delay in plant development and in an exacerbation of the negative effect of salinity in germination efficiency. We have also explored whether changes in expression of the endogenous AtMP have any effect on susceptibility to infection with several viruses, and found that the infectivity of tobacco rattle tobravirus was strongly dependent on the expression of the endogenous AtMP. Finally, we have cloned the endogenous MP from four different plant species into an expression vector that allows for specifically assessing their activity as cell-to-cell movement proteins and have shown that though some may still retain the ancestral activity, they do so in a quite inefficient manner, thus suggesting they have acquired a novel function during adaptation to the host genome.

evolutionary biology↗

Viral replication modes in single-peak fitness landscapes: a dynamical systems analysis

Positive-sense, single-stranded RNA viruses are important pathogens infecting almost all types of organisms. Experimental evidences from mutant distributions and amplification kinetics of viral RNA suggest that these pathogens may follow different RNA replication modes, ranging from the stamping machine replication (SMR) to the geometric replication (GR) modes. Despite previous theoretical works have focused on the evolutionary dynamics of RNA viruses amplifying their genomes with different strategies, few is known in terms of the bifurcations and transitions involving error thresholds (mutation-induced dominance of mutants) and lethal mutagenesis (mutation-induced extinction of all sequences). Here we analyze a dynamical system describing the intracellular amplification of viral RNA genomes evolving on a single-peak fitness landscape focusing on three cases considering neutral, deleterious, and lethal mutants spectra. In our model, the different replication modes are introduced with parameter : with {gtrsim} 0 for the SMR and = 1 for the GR. We analytically derive the critical mutation rates causing lethal mutagenesis and error catastrophe, governed by transcritical bifurcations that depend on parameters , k1 (replicative fitness of mutants), and on the spontaneous degradation rates of the sequences,{epsilon} . For the lethal case the critical mutation rate involving lethal mutagenesis is [Formula]. Here, the SMR involves lower critical mutation rates, being the system more robust to lethal mutagenesis replicating closer to the GR mode. This result is also found for the neutral and deleterious cases, but for these later cases lethal mutagenesis can shift to the error catastrophe once the replication mode surpasses a threshold given by [Formula].

systems biology↗

Diminishing returns of inoculum size on the rate of a plant RNA virus evolution

Understanding how genetic drift, mutation and selection interplay in determining the evolutionary fate of populations is one of the central questions of Evolutionary Biology. Theory predicts that by increasing the number of coexisting beneficial alleles in a population beyond some point does not necessarily translates into an acceleration in the rate of evolution. This diminishing-returns effect of beneficial genetic variability in microbial asexual populations is known as clonal interference. Clonal interference has been shown to operate in experimental populations of animal RNA viruses replicating in cell cultures. Here we carried out experiments to test whether a similar diminishing-returns of population size on the rate of adaptation exists for a plant RNA virus infecting real multicellular hosts. We have performed evolution experiments with tobacco etch potyvirus in two hosts, the natural and a novel one, at different inoculation sizes and estimated the rates of evolution for two phenotypic fitness-related traits. Firstly, we found that evolution proceeds faster in the novel than in the original host. Secondly, we found the predicted diminishing-returns effect of inoculum size on the rate of evolution for one of the fitness traits, but not for the other, which suggests that selection operates differently on each trait.

evolutionary biology↗

Spatially-induced nestedness in a neutral model of phage-bacteria networks

Ecological networks, both displaying mutualistic or antagonistic interactions, seem to share common structural traits: the presence of nestedness and modularity. A variety of model approaches and hypothesis have been formulated concerning the significance and implications of these properties. In phage-bacteria bipartite infection networks, nestedness seems to be the rule in many different contexts. Modeling the coevolution of a diverse virus-host ensemble is a difficult task, given the dimensionality and multi parametric nature of a standard continuous approximation. Here we show that this can actually be overcome by using a simple model of coevolving digital genomes on a spatial lattice and having exactly the same properties, i.e. a genome-independent fitness associated to fixed growth and death parameters. A matching allele model of phage-virus recognition rule is enough to generate a complex, diverse ecosystem with heterogeneous patterns of interaction and nestedness, provided that interactions take place under a spatially-constrained setting. It is found that nestedness seems to be an emergent property of the coevolutionary dynamics. Our results indicate that the enhanced diversity resulting from localized interactions strongly promotes the presence of nested infection matrices.

ecology↗