Evolutionary responses of fast adapting populations to opposing selection pressures

This thesis deals with the mathematical modeling of evolutionary processes that take place in heterogeneous populations. Its leitmotif is the response of complex ensembles of replicating entities to multiple (and often opposite) selection pressures. Even though the specific problems addressed in different chapters belong to different organizational levels—genome, population, and community—all of them can be conceptualized as the evolution of a heterogeneous population—let it be a population of genomic elements, viruses, or prokaryotic hosts and phages—facing a complex environment. As a result, the mathematical tools required for their study are quite similar. In contrast, the strategies that each population has discovered to perpetuate vary according to the different evolutionary challenges and environmental constraints that the population experiences. Along this thesis, there has been a special interest on connecting theoretical models with experimental results. To that end, most of the work presented here has been motivated either by laboratory findings or by the bioinformatic analysis of sequenced genomes. We strongly believe that such a multidisciplinary approach is necessary in order to improve our knowledge on how evolution works. Moreover, experiments are a must when it comes to propose antiviral strategies based on theoretical predictions, as we do in Chapter 3. This thesis is structured in two main blocks. The first one focuses on studying instances of viral evolution under the action of mutagenic drugs, paying particular attention to their possible application to the development of novel antiviral therapies. This block comprises chapters 2 and 3; the former dicussing the phenomenon of lethal defection and stochastic viral extinction; the latter dealing with the optimal way to combine mutagens and inhibitors in multidrug antiviral treatments. The second block is devoted to the study of the evolutionary forces underlying genome structure. In chapter 4, we propose a mechanism through which multipartite viruses could have originated. Interestingly, the pathway leading to genome segmentation shares some steps with lethal defection, but each outcome is reached at specific environmental conditions. Chapter 5 analyses the abundance distributions of transposable elements in prokaryotic genomes, with the aim of determining the key processes involved in their spreading. We explicitly explore the hypothesis that transposable elements follow a neutral dynamics, with a negligible fitness cost for their host genomes. A higher level of organization is studied in Chapter 6, where an agent based coevolutionary model based on Lotka-Volterra interactions is used to investigate the evolutionary dynamics of the prokaryotic antiviral immunity system CRISPR-Cas. This chapter also examines the environmental factors that are responsible for its maintenance or loss. Finally, Chapter 7 summarizes the main results obtained along the thesis and sketches possible lines of work based on them

Reply to Holmes and Duchêne, "Can Sequence Phylogenies Safely Infer the Origin of the Global Virome?": Deep Phylogenetic Analysis of RNA Viruses Is Highly Challenging but Not Meaningless

International audienc

Origins and evolution of the global RNA virome

Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (–) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas –RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy. IMPORTANCE The majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than was attainable previously. This reconstruction reveals the relationships between different Baltimore classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses