Horizontal gene transfer is an important factor in bacterial evolution that can act across species boundaries. Yet, we know little about rate and genomic targets of cross-lineage gene transfer, and about its effects on the recipient organism's physiology and fitness. Here, we address these questions in a parallel evolution experiment with two Bacillus subtilis lineages of 7% sequence divergence. We observe rapid evolution of hybrid organisms: gene transfer swaps ~12% of the core genome in just 200 generations, and 60% of core genes are replaced in at least one population. By genomics, transcriptomics, fitness assays, and statistical modeling, we show that transfer generates adaptive evolution and functional alterations in hybrids. Specifically, our experiments reveal a strong, repeatable fitness increase of evolved populations in the stationary growth phase. By genomic analysis of the transfer statistics across replicate populations, we infer that selection on HGT has a broad genetic basis: 40% of the observed transfers are adaptive. At the level of functional gene networks, we find signatures of negative and positive selection, consistent with hybrid incompatibilities and adaptive evolution of network functions. Our results suggest that gene transfer navigates a complex cross-lineage fitness landscape, bridging epistatic barriers along multiple high-fitness paths.
The cell invasion mechanism of Trypanosoma cruzi has similarities with some intracellular bacterial taxa especially regarding calcium mobilization. This mechanism is not observed in other trypanosomatids, suggesting that the molecules involved in this type of cell invasion were a product of (1) acquired by horizontal gene transfer; (2) secondary loss in the other trypanosomatid lineages of the mechanism inherited since the bifurcation Bacteria-Neomura (1.9 billion to 900 million years ago) or (3) de novo evolution from non-homologous proteins via convergent evolution. Similar to T. cruzi, seve…
Unraveling the evolutionary forces shaping bacterial diversity can today be tackled using a growing amount of genomic data. While the genome of eukaryotes is highly stable, bacterial genomes from cells of the same species highly vary in gene content. This huge variation in gene content led to the concepts of the distributed genome of bacteria and their pangenome (Tettelin et al.,2005; Ehrlich et al.,2005). We present a population genetic model for gene content evolution which accounts for several mechanisms. Gene uptake from the environment is modeled by events of gene gain along the genealogi…
The genome of bacterial species is much more flexible than that of eukaryotes. Moreover, the distributed genome hypothesis for bacteria states that the total number of genes present in a bacterial population is greater than the genome of every single individual. The pangenome, i.e. the set of all genes of a bacterial species (or a sample), comprises the core genes which are present in all living individuals, and accessory genes, which are carried only by some individuals. In order to use accessory genes for adaptation to environmental forces, genes can be transferred horizontally between indiv…
The evolution and emergence of antibiotic resistance is a major public health concern. The understanding of the within-host microbial dynamics combining mutational processes, horizontal gene transfer and resource consumption, is one of the keys to solve this problem. We analyze a generic model to rigorously describe interactions dynamics of four bacterial strains: one fully sensitive to the drug, one with mutational resistance only, one with plasmidic resistance only and one with both resistances. By dening thresholds numbers (i.e. each strain's eective reproduction and each strain's transitio…
The current picture of bacterial evolution is based largely on studies of 16S rRNA. However, this is just one gene. It is known that horizontal gene transfer can occur between bacterial species, although the frequency and implications of this are not fully understood. If horizontal transfer were frequent, there would be no single evolutionary tree for bacteria because each gene would follow a different tree. We carried out phylogenetic analyses of rRNA and tRNA genes from Proteobacteria (a diverse group for which many complete genome sequences are available) using RNA-specific phylogenetic met…
Bacteria, in contrast to eukaryotic cells contain two types of genes: chromosomal genes that are fixed to the cell, and plasmids that are mobile genes, easily shared to other cells. The sharing of plasmid genes between individual bacteria and between bacterial lineages has contributed vastly to bacterial evolution, allowing specialized traits to `jump ship' between one lineage or species and the next. The benefits of this generosity from the point of view of both recipient and plasmid are generally understood, but come at the expense of chromosomal genes in the donor cell, which share potentia…
Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid agar, and we develop a quantitative understanding by spatial extension of traditional mass-action models.…
Horizontal gene Transfer (HT) denotes the transmission of genetic material between two living organisms, while the vertical transmission refers to a DNA transfer from parents to their offspring. Consistent experimental evidence report that this phenomenon plays an essential role in the evolution of certain bacterias. In particular, HT is believed to be the main instrument of developing the antibiotic resistance. In this work, we consider several models which describe this phenomenon: a stochastic jump process (individual-based) and the deterministic nonlinear integrod-ifferential equation obta…
This paper develops a mathematical model describing the influence that conjugation-mediated Horizontal Gene Transfer (HGT) has on the mutation-selection balance in an asexually reproducing population of unicellular, prokaryotic organisms. It is assumed that mutation-selection balance is reached in the presence of a fixed background concentration of antibiotic, to which the population must become resistant in order to survive. We analyze the behavior of the model in the limit of low and high antibiotic-induced first-order death rate constants, and find that the highest mean fitness is obtained …
Pathogenic bacteria present a large disease burden on human health. Control of these pathogens is hampered by rampant lateral gene transfer, whereby pathogenic strains may acquire genes conferring resistance to common antibiotics. Here we introduce tools from topological data analysis to characterize the frequency and scale of lateral gene transfer in bacteria, focusing on a set of pathogens of significant public health relevance. As a case study, we examine the spread of antibiotic resistance in Staphylococcus aureus. Finally, we consider the possible role of the human microbiome as a reservo…
It is widely accepted that population genetics theory is the cornerstone of evolutionary analyses. Empirical tests of the theory, however, are challenging because of the complex relationships between space, dispersal, and evolution. Critically, we lack quantitative validation of the spatial models of population genetics. Here we combine analytics, on and off-lattice simulations, and experiments with bacteria to perform quantitative tests of the theory. We study two bacterial species, the gut microbe Escherichia coli and the opportunistic pathogen Pseudomonas aeruginosa, and show that spatio-ge…
Some bacteria and archaea possess an immune system, based on the CRISPR-Cas mechanism, that confers adaptive immunity against phage. In such species, individual bacteria maintain a "cassette" of viral DNA elements called spacers as a memory of past infections. The typical cassette contains a few dozen spacers. Given that bacteria can have very large genomes, and since having more spacers should confer a better memory, it is puzzling that so little genetic space would be devoted by bacteria to their adaptive immune system. Here, we identify a fundamental trade-off between the size of the bacter…
CRISPR is a newly discovered prokaryotic immune system. Bacteria and archaea with this system incorporate genetic material from invading viruses into their genomes, providing protection against future infection by similar viruses. The conditions for coexistence of prokaryots and viruses is an interesting problem in evolutionary biology. In this work, we show an intriguing phase diagram of the virus extinction probability, which is more complex than that of the classical predator-prey model. As the CRISPR incorporates genetic material, viruses are under pressure to evolve to escape the recognit…
We study the growth of a population of bacteria in a dynamical hostile environment corresponding to the immune system of the colonised organism. The immune cells evolve as subcritical open clusters of oriented percolation and are perpetually reinforced by an immigration process, while the bacteria try to grow as a supercritical oriented percolation in the remaining empty space. For appropriate values of the parameters, we prove that the population of bacteria grows linearly. In this perspective, we build general tools to study dependent percolation models issued from renormalization processes.
Motivated by recent research of aging in E. coli, we explore the effects of aging on bacterial fitness. The disposable soma theory of aging was developed to explain how differences in lifespans and aging rates could be linked to life history trade-offs. Although generally applied for multicellular organisms, it is also useful for exploring life history strategies of single celled organisms such as bacteria. Starting from the Euler-Lotka equation, we propose a mathematical model to explore how a finite lifespan effects fitness of bacteria. We find that that there is surprisingly little loss of …
Features of the CRISPR-Cas system, in which bacteria integrate small segments of phage genome (spacers) into their DNA to neutralize future attacks, suggest that its effect is not limited to individual bacteria but may control the fate and structure of whole populations. Emphasizing the population-level impact of the CRISPR-Cas system, recent experiments show that some bacteria regulate CRISPR-associated genes via the quorum sensing (QS) pathway. Here we present a model that shows that from the highly stochastic dynamics of individual spacers under QS control emerges a rank-abundance distribut…
Metagenomics has revealed hundreds of bacterial species in almost all microbiota. In a few well-studied cases, bacterial communities have been observed to coordinate their metabolic fluxes. In principle, bacteria can divide tasks to reap the benefits of specialization, as in human economies. However, the benefits and stability of an economy of bacterial specialists are far from obvious. Here, we physically model the population dynamics of bacteria that compete for steadily supplied resources. Importantly, we explicitly model the metabolic fluxes yielding cellular biomass production under the c…
A previously established multiscale population genetics model states that fitness can be inferred from the physical properties of proteins under the physiological assumption that a loss of stability by any protein confers the lethal phenotype to an organism. Here we develop this model further by positing that replication rate (fitness) of a bacterial or viral strain directly depends on the copy number of folded proteins which determine its replication rate. Using this model, and both numerical and analytical approaches, we studied the adaptation process of bacteria and viruses at varied enviro…
In this paper we develop and test algorithmic techniques to estimate genotypes fitnesses by analysis of observed daily frequency data monitoring the long-term evolution of bacterial populations. In particular, we develop a non-linear least squares approach to estimate selective advantages of emerging new mutant strains in locked-box stochastic models describing bacterial genetic evolution similar to the celebrated Lenski experiment on Escherichia Coli. Our algorithm first analyses emergence of new mutant strains for each individual trajectory. For each trajectory our analysis is progressive in…
In the context of bacteria and models of their evolution under genome rearrangement, we explore a novel application of group representation theory to the inference of evolutionary history. Our contribution is to show, in a very general maximum likelihood setting, how to use elementary matrix algebra to sidestep intractable combinatorial computations and convert the problem into one of eigenvalue estimation amenable to standard numerical approximation techniques.
Temporal evolution of a clonal bacterial population is modelled taking into account reversible mutation and selection mechanisms. For the mutation model, an efficient algorithm is proposed to verify whether experimental data can be explained by this model. The selection-mutation model has unobservable fitness parameters and, to estimate them, we use an Approximate Bayesian Computation (ABC) algorithm. The algorithms are illustrated using in vitro data for phase variable genes of Campylobacter jejuni.
