Biology subjects

Gordo, I.

Publications and source records attributed to Gordo, I..

17 recordsLinked to original sources

bioRxiv2026

Pervasive bacterial and prophage hybridization during chronic gut inflammation

Inflammatory bowel diseases (IBD) are modulated by microbiota composition, host genetics, and environmental factors1. Humans and other mammals are colonized by multiple strains of Escherichia coli, a species that expands in abundance in IBD patients2. The state of chronic inflammation characteristic of IBD is expected to intensify selective pressures on the gut microbial community, leading to distinct adaptive trajectories among its constituents. Here we couple in vivo experimental evolution with short- and long-read sequencing to test this hypothesis at the level of mutation and horizontal gene transfer (HGT). By colonizing IL10KO mice, a model of IBD3, and healthy wild-type mice with two strains of E. coli, we show that the tempo and mode of evolution are strain-specific and strongly shaped by host inflammatory status. Unique mutations associate with host inflammatory status independently of microbiota composition, and rates of transfer are diagnostic of chronic inflammation. Extensive transduction events occur in the inflamed gut, giving rise to hybrid clones that form a new genetic lineage, one that becomes dominant in this disease context. The high levels of recombination between prophages uncovered here point to a critical role of HGT and viral evolution in IBD.

microbiology↗

bioRxiv2025

Aging: an inevitable road toward gut microbiota pathoadaptation

Laboratory-raised mice live approximately seven times longer and healthier lives compared to their wild counterparts, due to a standardized healthy diet and limited exposure to environmental stressors1. Aging is associated with increased inflammation and microbial dysbiosis2-4. Collectively, these influence microbiota evolution and may contribute to the enrichment in pathobiont frequency observed in old age4. Alternatively, this increase could stem from a decline in colonization resistance5,6, creating favorable conditions for pathobiont invasion. Here, we sought to test whether aging in healthy, controlled conditions, could prevent the selection of age-associated pathobionts. We have followed the adaptive evolution of a commensal strain of Escherichia coli in the guts of mice of advanced age and found that it acquired several mutations common to bacteria colonizing young mice, which were absent in old animals. This, together with the increase in Akkermansia muciniphila in mice of advanced age, suggest healthy aging7,8. However, mutations acquired exclusively in the older were mainly pathoadaptive, tuning the metabolism to oxygen and iron availability, hypermotility, and biofilm formation. In summary, while the evolutionary signature in the guts of very old mice shows youth-like features that may be associated with longevity, the selection of pathoadaptive traits is magnified in very old age. While suggesting that a breach in colonization resistance is not needed to justify the abundance of age-associated pathobionts, our findings raise the question whether specialized bacteria, as opposing to generalists such as E. coli, will display the same ability to evolve pathoadaptive traits. HighlightsO_LIGut commensals face increasingly personalized selective pressures in the aging gut C_LIO_LIEven healthy aging selects for pathoadaptive traits in the gut microbiota C_LIO_LIE. coli s adaptive pattern better reflects the metabolome than microbiota composition C_LI In BriefPathobionts are often enriched in the microbiota of the elderly. Melo-Miranda et al. showed that irrespectively of limiting the opportunity for gut invasion, the strength of selection for pathoadaptation increases with aging. Yet, the gut environment of extreme ages seems to converge, highlighting the discontinuity of the aging process.

evolutionary biology↗

bioRxiv2023

Massive lateral gene transfer under strain coexistence in the gut

Mammals are colonized by multiple strains of Escherichia coli, yet how such strain coexistence affects their tempo and mode of evolution is poorly understood. Here, by following the colonization of two phylogenetic distinct strains of E. coli in the mouse gut, we find a strain-specific mode of evolution and a remarkable level of gene transfer between strains. In the same host, despite accumulating mutations at the same rate, one strain evolves by diversifying selection and the other by directional selection, and a rich dynamics of bacteriophage and plasmid transfer is found. Our results provide support for an important role of lateral transduction in the mammalian gut.

evolutionary biology↗

bioRxiv2023

Shared evolutionary path in social microbiomes

Social networks can influence the ecology of gut bacteria, shaping the species composition of the gut microbiome in humans and other animals. Gut commensals evolve and can adapt at a rapid pace when colonizing healthy hosts. Here, we aimed at assessing the impact of host-to-host bacterial transmission on Escherichia coli evolution in the mammalian gut. Using an in vivo experimental evolution approach in mice, we found a transmission rate of 7% ({+/-}3% 2SE) of E. coli cells per day between hosts inhabiting the same household. Consistent with the predictions of a simple population genetics model of mutation-selection-migration, the level of shared events resulting from within host evolution is greatly enhanced in co-housed mice, showing that hosts undergoing the same diet and habit are not only expected to have similar microbiome species compositions but also similar microbiome evolutionary dynamics. Furthermore, we estimated the rate of mutation accumulation of E. coli to be 2.9x10-3 ({+/-}5x10-4 2SE) mutations/genome/generation, irrespective of the social context of the regime. Our results reveal the impact of bacterial migration across hosts in shaping the adaptive evolution of new strains colonizing gut microbiomes.

evolutionary biology↗

bioRxiv2022

Epistasis decreases with increasing antibiotic pressure but not temperature

Predicting mutational effects is essential for the control of antibiotic resistance (ABR). Predictions are difficult when there are strong genotype-by-environment (GxE), gene-by-gene (GxG or epistatic), or gene- by-gene-by-environment (GxGxE) interactions. We quantified GxGxE effects in Escherichia coli across environmental gradients. We created intergenic fitness landscapes using gene knock-outs and single nucleotide ABR mutations previously identified to vary in the extent of GxE effects in our environments of interest. Then, we measured competitive fitness across a complete combinatorial set of temperature and antibiotic dosage gradients. In this way, we assessed the predictability of 15 fitness landscapes across 12 different but related environments. We found GxG interactions and rugged fitness landscapes in the absence of antibiotic, but as antibiotic concentration increased, the fitness effects of ABR genotypes quickly overshadowed those of gene knock-outs, and the landscapes became smoother. Our work reiterates that some single mutants, like those conferring resistance or susceptibility to antibiotics, have consistent effects across genetic backgrounds in stressful environments. Thus, although epistasis may reduce the predictability of evolution in benign environments, evolution may be more predictable in adverse environments.

evolutionary biology↗

bioRxiv2022

Two modes of evolution shape bacterial strain diversity in the gut for thousands of generations

How and at what pace bacteria evolve when colonizing healthy hosts remains unclear. Here, by monitoring evolution for more than six thousand generations in the mouse gut, we show that the successful colonization of an invader Escherichia coli depends on the diversity of the existing microbiota and the presence of a closely related strain. Following colonization, two modes of evolution were observed: one in which diversifying selection leads to long-term coexistence of ecotypes and a second in which directional selection propels selective sweeps. These modes can be quantitatively distinguished by the statistics of mutation trajectories. In our experiments, diversifying selection was marked by the emergence of metabolic mutations, and directional selection by acquisition of prophages, which bring their own benefits and costs. In both modes, we observed parallel evolution, with mutation accumulation rates comparable to those typically observed in vitro on similar time scales. Our results show that gut environments can rapidly generate diversifying selection and ecotype formation.

evolutionary biology↗

bioRxiv2021

Gut melange a trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics

Iron is critical in host-microbe interactions, and its availability is tightly regulated in the mammalian gut. Antibiotics and inflammation can perturb iron availability in the gut, which could alter host-microbe interactions. Here, we show that an adaptive allele of iscR, a major regulator of iron homeostasis of Escherichia coli, is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a hosts immune protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of iscR. Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.

evolutionary biology↗

bioRxiv2021

Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution

Background and objectivesTo understand how organisms evolve, it is fundamental to study how mutations emerge and establish. Here, we estimated the rate of mutation accumulation of SARS-CoV-2 in vitro and investigated the repeatability of its evolution when facing a new cell type but no immune or drug pressures. MethodologyWe performed experimental evolution with two strains of SARS-CoV-2, one carrying the originally described spike protein (CoV-2-D) and another carrying the D614G mutation that has spread worldwide (CoV-2-G). After 15 passages in Vero cells and whole genome sequencing, we characterized the spectrum and rate of the emerging mutations and looked for evidences of selection across the genomes of both strains. ResultsFrom the mutations accumulated, and excluding the genes with signals of selection, we estimate a spontaneous mutation rate of 1.25x10-6 nt-1 per infection cycle for both lineages of SARS-CoV-2. We further show that mutation accumulation is heterogeneous along the genome, with the spike gene accumulating mutations at rate five-fold higher than the genomic average. We also observe the emergence of mutators in the CoV-2-G background, likely linked to mutations in the RNA-dependent RNA polymerase and/or in the error-correcting exonuclease protein. Conclusions and implicationsThese results provide valuable information on how spontaneous mutations emerge in SARS-CoV-2 and on how selection can shape its genome towards adaptation to new environments. Lay summaryMutation is the ultimate source of variation. We estimated how the SARS-COV-2 virus--cause of the COVID-19 pandemic--mutates. Upon infecting cells, its genome can change at a rate of 0.04 per replication. We also find that this rate can change and that its spike protein can adapt, even within few replications.

evolutionary biology↗

bioRxiv2021

Epigenetic switching outcompetes genetic mutations during adaptation to fluctuating environments

Epigenetic inheritance allows for the emergence of phenotypic plasticity in clonal populations and enables the rapid stochastic switching between distinct phenotypes. In natural environments, where stress conditions can recurrently fluctuate, clones with an epigenetic control of genes targeted by selection should be fitter than clones that rely solely on genetic mutation. To test this prediction, we engineered switcher and non-switcher yeast strains, where the uracil biosynthesis gene URA3 is under fluctuating selection. Competitions of clones with an epigenetically controlled URA3 with clones without switching ability (SIR3 knock-out), show that epigenetic switching dominates under rapidly changing stresses. We further show that this advantage depends both on the switching rate and the period of environmental fluctuations. Remarkably, epigenetic clones with a high, but not with a low, rate of switching can co-exist with non-switchers even under a constant selective pressure, consistent with different constraints on the evolution of the rate of epigenetic switching.

evolutionary biology↗

bioRxiv2020

Molecular signatures of resource competition: clonal interference drives the emergence of ecotypes

Microbial ecosystems harbor an astonishing diversity that can persist for long times. To understand how such diversity is structured and maintained, ecological and evolutionary processes need to be integrated at similar timescales. Here, we study a model of resource competition that allows for evolution via de novo mutation, and focus on rapidly adapting asexual populations with large mutational inputs, as typical of many bacteria species. We characterize the adaptation and diversification of an initially maladapted population and show how the eco-evolutionary dynamics are shaped by the interaction between simultaneously emerging lineages - clonal interference. We find that in large populations, more intense clonal interference fosters diversification under sympatry, increasing the probability that phenotypically and genetically distinct clusters stably coexist. In smaller populations, the accumulation of deleterious and compensatory mutations can push further the diversification process and kick-start speciation. Our findings have implications beyond microbial populations, providing novel insights about the interplay between ecology and evolution in clonal populations.

evolutionary biology↗

bioRxiv2019

DNA breaks are key contributors to the cost of antibiotic resistance

Antibiotic resistance often generates a fitness cost to bacteria in drug-free environments. Understanding the causes of the cost is considered the Holy Grail in the antibiotic resistance field, as it is the main determinant of the prevalence of resistances upon reducing antibiotics use. We show that DNA breaks can explain most of the variation in the cost of resistances common in pathogens. Here we demonstrate that targeting the RNase that degrades R-loops, which cause DNA breaks, exacerbates the cost of resistance. Consequently, lack of RNase HI function drives resistant clones to extinction in populations with high initial frequency of resistance, both in laboratory conditions and in a mouse model of gut colonization. Thus, RNase HI provides a target specific against resistant bacteria, which we validate using a repurposed drug. In summary, we revealed key mechanisms underlying the cost of antibiotic resistance that can be exploited to specifically eliminate resistant bacteria.

microbiology↗

bioRxiv2019

Rampant loss of social traits during domestication of a wild Bacillus subtilis

Most well-studied bacteria have been domesticated to some extent. How fast can a natural isolate diverge from its ancestral phenotypes under domestication to a novel laboratory environment is poorly known. Yet such information is key to understand rates of evolution, the time scale at which a natural isolate can be propagated without loss of its natural adaptive traits and the reliability of experimental results across labs. Using experimental evolution, phenotypic assays and whole-genome sequencing, we show that within a week of propagation in a common laboratory environment, a natural isolate of Bacillus subtilis acquires mutations that cause changes in a multitude of traits. A single adaptive mutational step, in the gene coding for the transcriptional regulator DegU, impairs a DegU-dependent positive autoregulatory loop and leads to loss of robust biofilm architecture, impaired swarming motility, reduced secretion of exoproteases and changes in the dynamics of sporulation across environments. Importantly, domestication also resulted in improved survival when the bacteria face pressure from cells of the innate immune system. These results show that degU is a key target for mutations during domestication and also underscore the importance of performing careful and extremely short-term propagations of natural isolates to conserve the traits encoded in their original genomes. SummaryDomestication is the process by which organisms are selected to live in specific conditions and an important phenomenon that shapes the evolution and variation in many animals and plants. In microbes, domestication is also a key driver of adaptation. It can be beneficial, when improving microbes abilities that are important for biotechnology, but also problematic, especially when studying microbe-host interactions and the microbes natural behavior. Using a natural isolate of Bacillus subtilis, we determined the speed and genetic basis of microbial domestication using experimental evolution. Within one week of growth in the common laboratory media, mutations in the pleiotropic transcriptional regulator, DegU, emerge and spread in the populations. These lead to loss of social traits, increased resistance to bacteriophages and increased survival in the presence of macrophages. The data highlights the extreme caution that is needed when culturing natural microbial isolates and may help explain why some key microbial social traits and behaviors may differ between different laboratories, even when studying the same strains.

evolutionary biology↗

bioRxiv2019

Dysbiosis personalizes fitness effect of antibiotic resistance in the mammalian gut

The fitness cost of antibiotic resistance in the absence of antibiotics is crucial to the success of suspending antibiotics as a strategy to lower resistance. Here we show that after antibiotic treatment the cost of resistance within the complex ecosystem of the mammalian gut is personalized. Using mice as an in vivo model, we find that the fitness effect of the same resistant mutation can be deleterious in a host, but neutral or even beneficial in other hosts. Such antagonistic pleiotropy is shaped by the microbiota, as in germ-free mice resistance is consistently costly across all hosts. An eco-evolutionary model of competition for resources identifies a general mechanism underlying between host variation and predicts that the dynamics of compensatory evolution of resistant bacteria should be host specific, a prediction that was supported by experimental evolution in vivo. The microbiome of each human is close to unique and our results suggest that the short-term costs of resistance and its long-term within-host evolution will also be highly personalized, a finding that may contribute to the observed variable outcome of control therapies.\n\nOne Sentence SummaryPersonalized Fitness of Resistance Mutations.

evolutionary biology↗

bioRxiv2019

Low Mutational Load Allows for High Mutation Rate Variation in Gut Commensal Bacteria

Bacteria generally live in species-rich communities, such as the gut microbiota. Yet, little is known about bacterial evolution in natural ecosystems. Here, we followed the long-term evolution of commensal Escherichia coli in the mouse gut. We observe the emergence of polymorphism for mutation rate, ranging from wild-type levels to 1000-fold higher. By combining experiments, whole-genome sequencing and in silico simulations, we identify the molecular causes and evolutionary conditions that allow these hypermutators to emerge and coexist within a complex microbiota. The hypermutator phenotype is caused by mutations in DNA polymerase III, which increase mutation rate by ~1000-fold (a mutation in the proofreading subunit) and stabilize hypermutator fitness (mutations in the catalytic subunit). The strong mutation rate variation persists for >1000 generations, with coexistence between lineages carrying 4 to >600 mutations. This in vivo molecular evolution pattern is consistent with deleterious mutations of ~0.01-0.001% fitness effects, 100 to 1000-fold lower than current in vitro estimates. Despite large numbers of deleterious mutations, we identify multiple beneficial mutations that do not reach fixation over long periods of time. This indicates that the dynamics of beneficial mutations are not shaped by constant positive Darwinian selection but by processes leading to negative frequency-dependent or temporally fluctuating selection. Thus, microbial evolution in the gut is likely characterized by partial sweeps of beneficial mutations combined with hitchhiking of very slightly deleterious mutations, which take a long time to be purged but impose a very weak mutational load. These results are consistent with the pattern of genetic polymorphism that is emerging from metagenomics studies of the human gut microbiota, suggesting that we identified key evolutionary processes shaping the genetic composition of this community.

evolutionary biology↗

bioRxiv2018

Sex overrides mutation in Escherichia coli colonizing the gut

Bacteria evolve by mutation accumulation in laboratory experiments, but the tempo and mode of evolution in natural environments are largely unknown. Here we show, by experimental evolution of E. coli in the mouse gut, that the ecology of the gut controls bacterial evolution. If a resident E. coli strain is present in the gut, an invading strain evolves by rapid horizontal gene transfer; this mode precedes and outweighs evolution by point mutations. An epidemic infection by two phages drives gene uptake and produces multiple co-existing lineages of phage-carrying (lysogenic) bacteria. A minimal dynamical model explains the temporal pattern of phage epidemics and their complex evolutionary outcome as generic effects of phage-mediated selection. We conclude that phages are an important eco-evolutionary driving force - they accelerate evolution and promote genetic diversity of bacteria.\n\nOne Sentence SummaryBacteriophages drive rapid evolution in the gut.

evolutionary biology↗

bioRxiv2017

Cheating on orthogonal social traits prevents the tragedy of the commons in Pseudomonas aeruginosa

Bacterial cooperation can be disrupted by non-producers, which can profit from public goods without paying their production cost. A cheater can increase in frequency, exhausting the public good and causing a population collapse. Here we investigate how interactions among two cheaters for distinct social traits influence the short and long-term dynamics of polymorphic populations. Using as a model Pseudomonas aeruginosa and its extensively studied social traits, production of the siderophore pyoverdine and the quorum sensing regulated elastase, we analyzed the social dynamics of polymorphic populations under conditions where the two traits are required for optimal growth. We show that cheaters for either trait compete with both the wild type and each other, and that mutants for pyoverdine production can prevent a drastic population collapse caused by quorum sensing cheaters. A simple mathematical model suggests that the observed social dynamics are determined by the ratio of the costs of each social trait, such that the mutant which avoids paying the highest cost dominates the population. Finally, we demonstrate how quorum sensing regulation can avoid the full loss of cooperation.

genomics↗

bioRxiv2016

Rampant Reverse Evolution towards Specialization in Commensal Bacteria Colonizing the Gut

The maintenance of diversity in the gut microbiota is a signature of host health. Yet how strain variation emerges and changes over time in this ecosystem is poorly understood. Here we use a natural yet controlled system to track the effects of natural selection by the genetic signatures it leaves in evolving populations. By following the emergence of intra-species diversity in an Escherichia coli strain, we unravel a recurrent case of violation of Dollos law, which proposes that evolution is unidirectional and irreversible. We demonstrate de novo acquisition of a primordial lost phenotype via compensatory mutation and also genetic reversion, the latter leaving no trace of the past. We show that this reverse evolution generates two coexisting phenotypes, resource generalist and specialist, whose abundance can be controlled by diet supplementation. While specialists abundance is low, they avoid competition with the gut microbiota, whereas generalist abundance is dependent on microbiota composition. Our results highlight how a single genetic change can have large ecological consequences.

evolutionary biology↗