Biology subjects

Lucia-Sanz, A.

Publications and source records attributed to Lucia-Sanz, A..

5 recordsLinked to original sources

bioRxiv2024

Inferring strain-level mutational drivers of phage-bacteria interaction phenotypes

The enormous diversity of bacteriophages and their bacterial hosts presents a significant challenge to predict which phages infect a focal set of bacteria. Infection is largely determined by complementary - and largely uncharacterized - genetics of adsorption, injection, cell take-over and lysis. Here we present a machine learning approach to predict phage-bacteria interactions trained on genome sequences of and phenotypic interactions amongst 51 Escherichia coli strains and 45 phage{lambda} strains that coevolved in laboratory conditions for 37 days. Leveraging multiple inference strategies and without a priori knowledge of driver mutations, this framework predicts both who infects whom and the quantitative levels of infections across a suite of 2,295 potential interactions. We found that the most effective approach inferred interaction phenotypes from independent contributions from phage and bacteria mutations, accurately predicting 86% of interactions while reducing the relative error in the estimated strength of the infection phenotype by 40%. Feature selection revealed key phage{lambda} and E. coli mutations that have a significant influence on the outcome of phage-bacteria interactions, corroborating sites previously known to affect phage{lambda} infections, as well as identifying mutations in genes of unknown function not previously shown to influence bacterial resistance. The methods success in recapitulating strain-level infection outcomes arising during coevolutionary dynamics may also help inform generalized approaches for imputing genetic drivers of interaction phenotypes in complex communities of phage and bacteria.

bioinformatics↗

bioRxiv2023

Rapid bacteria-phage coevolution drives the emergence of multi-scale networks

Interactions between species have catalyzed the evolution of multiscale ecological networks-including both nested and modular elements that regulate the function of diverse communities. One common assumption is that such complex pattern formation requires long evolutionary timescales, spatial isolation, or other exogenous processes. Here we show that multiscale network structure can evolve rapidly under simple ecological conditions without spatial structure. In just 21 days of laboratory coevolution, Escherichia coli and bacteriophage {Phi}21 coevolve and diversify to form elaborate cross-infection networks. By measuring [~]10,000 phage-bacteria infections and testing the genetic basis of interactions, we identify the mechanisms that create each component of the multiscale pattern. Initially, nested patterns form through an arms race where hosts successively lose the original receptor (LamB) and phages evolve to use a second (OmpC) and then a third (OmpF) receptor. Next, modules form when the cost of losing the third receptor, OmpF, increases and bacteria evolve resistance mutations that modify the OmpF receptors extramembrane loops. In turn, phages evolve adaptations that facilitate specialized interactions with different OmpF variants. Nestedness reemerges within modules as bacteria evolve increased resistance and phages enhance infectivity against module-specific receptor variants. Our results demonstrate how multiscale networks evolve in parasite-host systems, illustrating Darwins idea that simple adaptive processes can generate entangled banks of ecological interactions.

evolutionary biology↗

bioRxiv2022

Defective subviral particles modify ecological equilibria and enhance viral coexistence

Cooperation is a main driver of biological complexity at all levels. In the viral world, gene sharing among viral genomes, complementation between genomes or interactions within quasispecies are frequently observed. In this contribution, we explore the advantages that flexible associations between fully fledged viruses and subviral entities, such as virus satellites, might yield. We devise a mathematical model to compare different situations of competition between two viruses and to quantify how the association with a satellite qualitatively modifies dynamical equilibria. The relevant parameter is the invasion fitness of each virus or of the virus-satellite tandem, which in the model depends on the transmission rate of viruses and on their effect on host survival. While in a virus-virus competition one of the viruses becomes eventually extinct, an association with a satellite might change the outcome of the competition to favor the less competitive virus (regardless of whether it is the helper virus or not) or to allow for the stable coexistence of the two viruses and the satellite. We hypothesize that the latter scenario, in particular, constitutes a parsimonious evolutionary pathway towards more stable cooperative associations, such as bipartite viral forms.

ecology↗

bioRxiv2021

Time-scales modulate optimal lysis-lysogeny decision switches and near-term phage fitness

Temperate phage can initiate lysis or lysogeny after infecting a bacterial host. The genetic switch between lysis and lysogeny is mediated by phage regulatory genes as well as host and environmental factors. Recently, a new class of decision switches was identified in phage of the SPbeta group, mediated by the extracellular release of small, phage-encoded peptides termed arbitrium. Arbitrium peptides can be taken up by bacteria prior to infection, modulating the decision switch in the event of a subsequent phage infection. Increasing concentration of arbitrium increases the chance that a phage infection will lead to lysogeny, rather than lysis. Although prior work has centered on the molecular mechanisms of arbitrium-induced switching, here we focus on how selective pressures impact the benefits of plasticity in switching responses. In this work, we examine the possible advantages of near-term adaptation of communication-based decision switches used by the SPbeta-like group. We combine a nonlinear population model with a control theoretic approach to evaluate the relationship between a putative phage reaction norm (i.e., the probability of lysogeny as a function of arbitrium) and the near-term time horizon. We show the adaptive potential of communication-based lysis-lysogeny responses and find that optimal switching between lysis to lysogeny increases near-term fitness compared to fixed responses. We further find that plastic responses are robust to the inclusion of cellular-level stochasticity. These findings provide a principled basis to explore the long-term evolution of phage-encoded decision systems mediated by extracellular decision-signaling molecules, and the feedback between phage reaction norms and ecological context.

ecology↗

bioRxiv2018

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 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 which include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded (ds) RNA 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, particularly, 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.\n\nIMPORTANCEThe 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 what 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.

microbiology↗