Biology subjects

Cury, J.

Publications and source records attributed to Cury, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Rapid modular evolution of antiviral repertoires in P2 phages and their P4 satellites: shuttling, swapping and mixing

Interactions between bacteria, bacteriophages, and their satellites are shaped by a myriad of defence and counter-defence mechanisms. Here, we identified and characterized the defence hotspots of thousands of P2-like phages and P4-like satellites to elucidate the origins and evolutionary dynamics of defence systems. Both P4 and P2 encode a broad diversity of recognizable defence systems. Defences are a substantial, yet likely underestimated, share of the elements pangenomes, as shown by novel antiviral functions discovered in P4 loci lacking known defence genes. Defence loci are very rapidly swapped, without pseudogenization, suggesting defences are replaced before becoming non-adaptive. This intense local recombination melds components of distinct systems into novel functional chimeras. Systems swap so rapidly that many elements with identical core genes have completely different defences. Surprisingly, despite P4 and P2s concomitant replication and packaging, they almost never exchange defence genes. In contrast, near identical defence systems can be found in distinct types of MGEs and in cryptic chromosomal locations. Our findings highlight P4 and P2 as mobile platforms driving the modular diversification of bacterial antiviral repertoires. Hence, bacterial defences change quickly by phage and satellite turnover, and by the quick swap of defences within these elements.

microbiology↗

bioRxiv2025

Ancient genomic insights into Salmonella enterica Paratyphi C in Central Mexico

Salmonella enterica is a widespread pathogen of major global health relevance, with over 2,500 serovars classified into non-typhoidal and typhoidal groups. Within the typhoidal group, S. enterica Paratyphi C causes paratyphoid fever in humans. Ancient DNA from this bacterium has previously been recovered from epidemic-associated burials in Eurasia and Mexico, dating back 6,000 to 300 years. Here, we analyzed dental DNA from seven individuals (radiocarbon dated to 1800-1940 CE) buried at the Temple of the Immaculate Conception in Mexico City, Central Mexico, and identified ancient S. enterica Paratyphi C DNA in a young female with Native American ancestry. Using an in-house targeted enrichment strategy and deep shotgun sequencing, we reconstructed a S. enterica Paratyphi C genome (COYC5) with [~]11X coverage. Phylogenetic and comparative genomic analyses place COYC5 in close association with previously reported S. enterica Paratyphi C genomes associated with the 1545 cocoliztli epidemic in southern Mexico, as well as with European strains. Divergence estimates indicate that the Mexican and European lineages shared a common ancestor approximately 1,400 years before present (yBP), reflecting an ancient evolutionary split predating European colonization of Mexico. In contrast, the divergence between COYC5 and the southern Mexican genomes occurred around 516 yBP, coinciding with the onset of the colonial period. This pattern supports a European introduction of S. enterica Paratyphi C during colonization, followed by its local diversification within Mexico. Despite this regional differentiation, the conserved presence of key virulence loci--such as SPI-7 and an active shufflon system--across COYC5, southern Mexican, and European genomes underscores the enduring pathogenic potential of S. enterica Paratyphi C. The identification of this bacterium in 19th-century Mexico City provides the first genomic evidence of its persistence in urban contexts beyond major epidemic outbreaks, offering new insights into its evolutionary trajectory in Mexico. These findings raise new questions about how the pathogen spread and persisted across different ecological, social, and epidemiological contexts in ancient Mexico and the Americas.

evolutionary biology↗

bioRxiv2025

Protein and genomic language models chart a vast landscape of antiphage defenses

The bacterial pangenome encodes an immense array of antiphage systems, yet much of their diversity remains uncharted. In this study, we developed language models to predict novel antiphage proteins in two ways: first via fine-tuning ESM2, a protein language model capable of detecting distant homology to known defense proteins, second via a genomic language model with ALBERT architecture which predicts defensive function based on genomic context. We demonstrate that applying these approaches to Actinomycetota - a phylum largely unexplored for antiphage defenses, can accurately predict previously unknown functional defense mechanisms, leading to the discovery and experimental validation of six defense systems with novel antiphage proteins. Analysis of over 30,000 bacterial genomes predicted more than 45,000 uncharacterized protein families potentially involved in antiphage defense, underscoring the vast, untapped diversity of these systems.

microbiology↗

bioRxiv2024

A human homolog of SIR2 antiphage proteins mediates immunity via the TLR pathway

The full extent of immune system conservation between prokaryotes and eukaryotes is unknown. However, recent research supports that a subset of bacterial antiphage proteins is conserved in eukaryotes and likely gave rise to key actors of mammalian immunity. Here, we show that the SIR2 protein domain, present in bacterial antiphage systems, plays a role in eukaryotic innate immunity. Through phylogenetic analysis, we identify SIRanc, a human protein with a SIRim domain (subtype of SIR2). We demonstrate that SIRanc plays a pivotal role in the animal toll-like receptor (TLR) pathway of innate immunity by mediating the transcriptional upregulation of proinflammatory genes downstream of TLR stimulation. This depends on the enzymatic activity of SIRanc, which degrades NAD+, a central cellular metabolite. Finally, we show that proteins with a SIRim domain are diverse and widespread, detected in 19% of eukaryotic genomes, with SIRanc representing one of the five sirim lineages. This work opens avenues of research on the potential role of eukaryotic SIRim proteins in immunity, as well as on the involvement of SIRanc in human pathology.

immunology↗

bioRxiv2024

Essential and dual effects of Notch activity on a natural transdifferentiation event

Cell identity can be reprogrammed, naturally or experimentally, albeit with low frequency. Why given cells, but not their neighbours, undergo a cell identity conversion remains unclear. We find that Notch signalling plays a key role to promote natural transdifferentiation in C. elegans. Endogenous Notch signal endows a cell with the competence to transdifferentiate by promoting plasticity factors expression (hlh-16/Olig and sem-4/Sall). Strikingly, exogenous Notch can trigger ectopic transdifferentiation in vivo. However, Notch signalling can both promote and block transdifferentiation depending on its activation timing. Notch only promotes transdifferentiation during an early precise window of opportunity and signal duration must be tightly controlled in time. Our findings emphasise the importance of temporality and dynamics of the underlying molecular events preceding the initiation of natural cell reprogramming. Finally, our results support a model where both an extrinsic signal and the intrinsic cellular context combine to empower a cell with the competence to transdifferentiate.

developmental biology↗

bioRxiv2024

Exploring the diversity of anti-defense systems across prokaryotes, phages, and mobile genetic elements

The co-evolution of prokaryotes, phages, and mobile genetic elements (MGEs) over the past billions of years has driven the emergence and diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences, and are typically small, creating a challenge to detect anti-defense homologs across the prokaryotic genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired genome or MGE. Here, we developed "AntiDefenseFinder" - a free open-source tool and web service that detects 156 anti-defense systems (of one or more proteins) in any genomic sequence. Using this dataset, we identified 47,981 anti-defense systems distributed across prokaryotes, phage, and MGEs. We found that some genes co-localize in "anti-defense islands", including E. coli T4 and Lambda phages, although many are standalone. Out of the 112 systems detected in bacteria, 100 systems localize only or preferentially in prophages, plasmids, phage satellites, integrons, and integrative and conjugative elements. However, over 80% of anti-Pycsar protein 1 (Apyc1) resides in non-mobile regions of bacteria. Evolutionary and functional analyses revealed that Apyc1 likely originated in bacteria to regulate cNMP signaling, but was co-opted multiple times by phages to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions, and a deeper understanding of host-pathogen arms race.

microbiology↗

bioRxiv2024

Evolutionary origins of archaeal and eukaryotic RNA-guided RNA modification in bacterial IS110 transposons

Transposase genes are ubiquitous in all domains of life and provide a rich reservoir for the evolution of novel protein functions. Here we report deep evolutionary links between bacterial IS110 transposases, which catalyze RNA-guided DNA recombination using bridge RNAs, and archaeal/eukaryotic Nop5-family proteins, which promote RNA-guided RNA 2-O-methylation using C/D-box snoRNAs. Based on conservation in the protein primary sequence, domain architecture, and three-dimensional structure, as well as common architectural features of the non-coding RNA components, we propose that programmable RNA modification emerged via exaptation of components derived from IS110-like transposons. Alongside recent studies highlighting the origins of CRISPR-Cas9 and Cas12 in IS605-family transposons, these findings underscore how recurrent domestication events of transposable elements gave rise to complex RNA-guided biological mechanisms.

evolutionary biology↗

bioRxiv2024

A mechanistic step in the genesis of secondary chromosomes from plasmids

Bacterial genomes contain a plethora of secondary replicons of divergent size. Circular replicons must carry a system for resolving dimeric forms, resulting from recombination between sister copies. These systems use site-specific recombinases. Among these, the XerCD recombinase resolves dimers of chromosomes and certain plasmids using different controls. We have analyzed the dimer resolution functions in enterobacterial secondary replicons and show that, in addition to the main chromosomes, XerCD is preferentially used by small plasmids and by the largest secondary replicons, megaplasmids and secondary chromosomes. Indeed, all replicons longer than 250 kb host an active XerCD recombination site. These sites, in contrast to those of small plasmids, use the same control as chromosomes, coupled to cell division by the FtsK protein. We conclude that a chromosome-like mode of dimer resolution is mandatory for the faithful inheritance of large plasmids and chromids, its acquisition being a prerequisite for the genesis of secondary chromosomes from plasmids.

microbiology↗

bioRxiv2024

A Comprehensive Resource for Exploring Antiphage Defense: DefenseFinder Webservice, Wiki and Databases.

In recent years, a vast number of novel antiphage defense mechanisms were uncovered. To facilitate the exploration of mechanistic, ecological, and evolutionary aspects related to antiphage defense systems, we released DefenseFinder in 2021 (Tesson et al., 2022). DefenseFinder is a bioinformatic program designed for the systematic identification of known antiphage defense mechanisms. The initial release of DefenseFinder v1.0.0 included 60 systems. Over the past three years, the number of antiphage systems incorporated into DefenseFinder has grown to 152. The increasing number of known systems makes it a challenge to enter the field and makes the interpretation of detections of antiphage systems difficult. Moreover, the rapid development of sequence-based predictions of structures offers novel possibilities of analysis and should be easily available. To overcome these challenges, we present a hub of resources on defense systems, including: 1) an updated version of DefenseFinder with a web-service search function, 2) a community-curated repository of knowledge on the systems, and 3) precomputed databases, which include annotations done on RefSeq genomes and structure predictions generated by AlphaFold. These pages can be freely accessed for users as a starting point on their journey to better understand a given system. We anticipate that these resources will foster the use of bioinformatics in the study of antiphage systems and will serve the community of researchers who study antiphage systems. This resource is available at: https://defensefinder.mdmlab.fr.

genomics↗

bioRxiv2023

Viperin immunity evolved across the tree of life through serial innovations on a conserved scaffold

Evolutionary arms races between cells and viruses drive the rapid diversification of antiviral genes in diverse life forms. Recent discoveries have revealed the existence of shared immune genes between prokaryotes and eukaryotes, showing molecular and mechanistic similarities in their response to viruses. However, the underlying evolutionary dynamics that explain the conservation and adaptation of these antiviral genes remain mostly unexplored. Here, we show that viperins constitute a highly conserved family of immune genes across diverse prokaryotes and eukaryotes, and uncover mechanisms by which they diversified in eukaryotes. Our findings indicate that viperins are enriched in Asgard archaea and widely distributed in all major eukaryotic clades, suggesting their presence in the Last Eukaryotic Common Ancestor (LECA). We show that viperins maintain their immune function by producing antiviral nucleotide analogs. We demonstrate that eukaryotic viperins diversified through serial innovations on the viperin gene, such as the emergence and selection of substrate specificity towards pyrimidine nucleotides, and through partnerships with genes maintained through genetic linkage, notably with nucleotide kinases. These findings unveil biochemical and genomic transitions underlying the adaptation of immune genes shared by prokaryotes and eukaryotes. Our study paves the way for the understanding of the conservation of immunity across domains of life.

evolutionary biology↗

bioRxiv2022

Conservation of antiviral systems across domains of life reveals novel immune mechanisms in humans

Viral infection is a common threat to prokaryotic and eukaryotic life, which has resulted in the evolution of a myriad of antiviral systems. Some of these eukaryotic systems are thought to have evolved from prokaryotic antiphage proteins, with which they may display sequence and structural homology. Here, we show that homologs of recently discovered antiphage systems are widespread in eukaryotes. We demonstrate that such homologs can retain a function in immunity by unveiling that eukaryotic proteins of the anti-transposon piRNA pathway display domain homology with the antiphage system Mokosh. We further utilise this conservation to discover novel human antiviral genes related to the Eleos and Lamassu prokaryotic systems. We propose that comparative immunology across domains of life can be leveraged to discover immune genes in eukaryotes.

genomics↗

bioRxiv2022

Expanding the stdpopsim species catalog, and lessons learned forrealistic genome simulations

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic data sets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and to the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than three-fold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.

bioinformatics↗

bioRxiv2022

A new route for integron cassette dissemination among bacterial genomes

Integrons are genetic elements involved in bacterial adaptation. They can capture, shuffle and express adaptive functions embedded in cassettes. These events are governed by the integron integrase through site-specific recombination between attC and attI integron sites. Here, we demonstrated that the integrase can efficiently catalyze insertion of cassettes in bacterial genomes, outside the att sites. We showed that, once inserted in genomes, cassettes can be expressed, if located near bacterial promoters, and can be excised at the insertion point and even outside, inducing chromosomal modifications in the latter case. Analysis of more than 5 x 105 independent insertion events revealed a very large genomic insertion landscape with recombination sites greatly different, in terms of sequence and structure, from classical att sites. We named these new sites attG. These results unveil a new efficient route for dissemination of adaptive functions and expand the role of integrons in bacterial evolution.

genetics↗

bioRxiv2022

Cultural transmission of reproductive success impacts genomic diversity, coalescent tree topologies and demographic inferences

Cultural Transmission of Reproductive Success (CTRS) has been observed in many human populations as well as other animals. It consists in a positive correlation of non-genetic origin between the progeny size of parents and children. This correlation can result from various factors, such as the social influence of parents on their children, the increase of childrens survival through allocare from uncle and aunts, or the transmission of resources. Here, we study the evolution of genomic diversity through time under CTRS. We show that CTRS has a double impact on population genetics: (1) effective population size decreases when CTRS starts, mimicking a population contraction, and increases back to its original value when CTRS stops; (2) coalescent trees topologies are distorted under CTRS, with higher imbalance and higher number of polytomies. Under long-lasting CTRS, effective population size stabilises but the distortion of tree topology remains, which yields U-shaped Site Frequency Spectra (SFS) under constant population size. We show that this CTRS impact yields a bias in SFS-based demographic inference. Considering that CTRS was detected in numerous human and animal populations worldwide, one should be cautious that inferring population past histories from genomic data can be biased by this cultural process.

genetics↗

bioRxiv2022

IntegronFinder 2.0: identification and analysis of integrons across Bacteria, with a focus on antibiotic resistance in Klebsiella

Integrons are mobile genetic elements that contain multiple cassettes encoding accessory genes whose order is shuffled by a specific integrase. Integrons within mobile genetic elements often contain multiple antibiotic resistance genes that they spread among nosocomial pathogens and contribute to the current antibiotic resistance crisis. However, most integrons are presumably sedentary and encode a much broader diversity of functions. IntegronFinder is a widely used software to identify novel integrons in bacterial genomes, but has aged and lacks some useful functionalities to handle very large datasets of draft genomes or metagenomes. Here, we present IntegronFinder version 2. We have updated the code, improved its efficiency and usability, adapted the output to incomplete genome data, and added a few novel functions. We describe these changes and illustrate the relevance of the program by analyzing the distribution of integrons across more than 20,000 fully sequenced genomes. We also take full advantage of its novel capabilities to analyze close to 4 thousand Klebsiella pneumoniae genomes for the presence of integrons and antibiotic resistance genes within them. Our data shows that K. pneumoniae has a large diversity of integrons and the largest mobile integron in our database of plasmids. The pangenome of these integrons contains a total of 165 different gene families with most of the largest families being related with resistance to numerous types of antibiotics. IntegronFinder is a free and open-source software available at https://github.com/gem-pasteur/Integron_Finder.

bioinformatics↗

bioRxiv2021

Systematic and quantitative view of the antiviral arsenal of prokaryotes

Facing the abundance and diversity of phages, bacteria have developed multiple anti-phage mechanisms. In the past three years, the number of known anti-phage mechanisms has been expanded by at least 5-fold rendering our view of prokaryotic immunity obsolete. Most anti-phage systems have been studied as standalone mechanisms, however many examples demonstrate strains encode not one but several anti-viral mechanisms. How these different systems integrate into an anti-viral arsenal at the strain level remains to be elucidated. Much could be learned from establishing fundamental description of features such as the number and diversity of anti-phage systems encoded in a given genome. To address this question, we developed DefenseFinder, a tool that automatically detects known anti-phage systems in prokaryotic genomes. We applied DefenseFinder to >20 000 fully sequenced genomes, generating a systematic and quantitative view of the anti-viral arsenal of prokaryotes. We show prokaryotic genomes encode on average five anti-phage systems from three different families of systems. This number varies drastically from one strain to another and is influenced by the genome size and the number of prophages encoded. Distributions of different systems are also very heterogenous with some systems being enriched in prophages and in specific clades. Finally, we provide a detailed comparison of the anti-viral arsenal of 15 common bacterial species, revealing drastic differences in anti-viral strategies. Overall, our work provides a free and open-source software, available as a command line tool or, on a webserver. It allows the rapid detection of anti-phage systems, enables a comprehensive description of the anti-viral arsenal of prokaryotes and paves the way for large scale genomics study in the field of anti-phage defense.

microbiology↗

bioRxiv2020

Simulation of bacterial populations with SLiM

Simulation of genomic data is a key tool in population genetics, yet, to date, there is no forward-in-time simulator of bacterial populations that is both computationally efficient and adaptable to a wide range of scenarios. Here we demonstrate how to simulate bacterial populations with SLiM, a forward-in-time simulator built for eukaryotes. SLiM has gained many users in recent years, due to its speed and power, and has extensive documentation showcasing various scenarios that it can simulate. This paper focuses on a simple demographic scenario, to explore unique aspects of modeling bacteria in SLiMs scripting language. In addition, we illustrate the flexibility of SLiM by simulating the growth of bacteria on a Petri dish with antibiotic. To foster the development of bacterial simulations based upon this recipe, we explain the inner workings of its code. We also validate the simulator, by extensively testing the results of simulations against existing simulators, and against theoretical expectations for some summary statistics. This protocol, with the flexibility and power of SLiM, will enable the community to simulate bacterial populations efficiently under a wide range of evolutionary scenarios.

evolutionary biology↗

bioRxiv2020

Deep learning for population size history inference: design, comparison and combination with approximate Bayesian computation

AO_SCPLOWBSTRACTC_SCPLOWFor the past decades, simulation-based likelihood-free inference methods have enabled researchers to address numerous population genetics problems. As the richness and amount of simulated and real genetic data keep increasing, the field has a strong opportunity to tackle tasks that current methods hardly solve. However, high data dimensionality forces most methods to summarize large genomic datasets into a relatively small number of handcrafted features (summary statistics). Here we propose an alternative to summary statistics, based on the automatic extraction of relevant information using deep learning techniques. Specifically, we design artificial neural networks (ANNs) that take as input single nucleotide polymorphic sites (SNPs) found in individuals sampled from a single population and infer the past effective population size history. First, we provide guidelines to construct artificial neural networks that comply with the intrinsic properties of SNP data such as invariance to permutation of haplotypes, long scale interactions between SNPs and variable genomic length. Thanks to a Bayesian hyperparameter optimization procedure, we evaluate the performance of multiple networks and compare them to well established methods like Approximate Bayesian Computation (ABC). Even without the expert knowledge of summary statistics, our approach compares fairly well to an ABC based on handcrafted features. Furthermore we show that combining deep learning and ABC can improve performance while taking advantage of both frameworks. Finally, we apply our approach to reconstruct the effective population size history of cattle breed populations.

evolutionary biology↗