Differential Regulation of Horizontally Acquired and Core Genome Genes by the Bacterial Modulator H-NS

Horizontal acquisition of DNA by bacteria dramatically increases genetic diversity and hence successful bacterial colonization of several niches, including the human host. A relevant issue is how this newly acquired DNA interacts and integrates in the regulatory networks of the bacterial cell. The global modulator H-NS targets both core genome and HGT genes and silences gene expression in response to external stimuli such as osmolarity and temperature. Here we provide evidence that H-NS discriminates and differentially modulates core and HGT DNA. As an example of this, plasmid R27-encoded H-NS protein has evolved to selectively silence HGT genes and does not interfere with core genome regulation. In turn, differential regulation of both gene lineages by resident chromosomal H-NS requires a helper protein: the Hha protein. Tight silencing of HGT DNA is accomplished by H-NS-Hha complexes. In contrast, core genes are modulated by H-NS homoligomers. Remarkably, the presence of Hha-like proteins is restricted to the Enterobacteriaceae. In addition, conjugative plasmids encoding H-NS variants have hitherto been isolated only from members of the family. Thus, the H-NS system in enteric bacteria presents unique evolutionary features. The capacity to selectively discriminate between core and HGT DNA may help to maintain horizontally transmitted DNA in silent form and may give these bacteria a competitive advantage in adapting to new environments, including host colonization.     

The transferome of metabolic genes explored: analysis of the horizontal transfer of enzyme encoding genes in unicellular eukaryotes

Background  

Metabolic networks are responsible for many essential cellular processes, and exhibit a high level of evolutionary conservation from bacteria to eukaryotes. If genes encoding metabolic enzymes are horizontally transferred and are advantageous, they are likely to become fixed. Horizontal gene transfer (HGT) has played a key role in prokaryotic evolution and its importance in eukaryotes is increasingly evident. High levels of endosymbiotic gene transfer (EGT) accompanied the establishment of plastids and mitochondria, and more recent events have allowed further acquisition of bacterial genes. Here, we present the first comprehensive multi-species analysis of E/HGT of genes encoding metabolic enzymes from bacteria to unicellular eukaryotes.     

Horizontal gene transfer in eukaryotes: The weak‐link model

The significance of horizontal gene transfer (HGT) in eukaryotic evolution remains controversial. Although many eukaryotic genes are of bacterial origin, they are often interpreted as being derived from mitochondria or plastids. Because of their fixed gene pool and gene loss, however, mitochondria and plastids alone cannot adequately explain the presence of all, or even the majority, of bacterial genes in eukaryotes. Available data indicate that no insurmountable barrier to HGT exists, even in complex multicellular eukaryotes. In addition, the discovery of both recent and ancient HGT events in all major eukaryotic groups suggests that HGT has been a regular occurrence throughout the history of eukaryotic evolution. A model of HGT is proposed that suggests both unicellular and early developmental stages as likely entry points for foreign genes into multicellular eukaryotes.     

Inter-phylum HGT has shaped the metabolism of many mesophilic and anaerobic bacteria

Genome sequencing has revealed that horizontal gene transfer (HGT) is a major evolutionary process in bacteria. Although it is generally assumed that closely related organisms engage in genetic exchange more frequently than distantly related ones, the frequency of HGT among distantly related organisms and the effect of ecological relatedness on the frequency has not been rigorously assessed. Here, we devised a novel bioinformatic pipeline, which minimized the effect of over-representation of specific taxa in the available databases and other limitations of homology-based approaches by analyzing genomes in standardized triplets, to quantify gene exchange between bacterial genomes representing different phyla. Our analysis revealed the existence of networks of genetic exchange between organisms with overlapping ecological niches, with mesophilic anaerobic organisms showing the highest frequency of exchange and engaging in HGT twice as frequently as their aerobic counterparts. Examination of individual cases suggested that inter-phylum HGT is more pronounced than previously thought, affecting up to ∼16% of the total genes and ∼35% of the metabolic genes in some genomes (conservative estimation). In contrast, ribosomal and other universal protein-coding genes were subjected to HGT at least 150 times less frequently than genes encoding the most promiscuous metabolic functions (for example, various dehydrogenases and ABC transport systems), suggesting that the species tree based on the former genes may be reliable. These results indicated that the metabolic diversity of microbial communities within most habitats has been largely assembled from preexisting genetic diversity through HGT and that HGT accounts for the functional redundancy among phyla.     

An ancient horizontal gene transfer between mosquito and the endosymbiotic bacterium Wolbachia pipientis

The extent and biological relevance of horizontal gene transfer (HGT) in eukaryotic evolution remain highly controversial. Recent studies have demonstrated frequent and large-scale HGT from endosymbiotic bacteria to their hosts, but the great majority of these transferred genes rapidly become nonfunctional in the recipient genome. Here, we investigate an ancient HGT between a host metazoan and an endosymbiotic bacterium, Wolbachia pipientis. The transferred gene has so far been found only in mosquitoes and Wolbachia. In mosquitoes, it is a member of a gene family encoding candidate receptors required for malaria sporozoite invasion of the mosquito salivary gland. The gene copy in Wolbachia has substantially diverged in sequence from the mosquito homolog, is evolving under purifying selection, and is expressed, suggesting that this gene is also functional in the bacterial genome. Several lines of evidence indicate that the gene may have been transferred from eukaryotic host to bacterial endosymbiont. Regardless of the direction of transfer, however, these results demonstrate that interdomain HGT may give rise to functional, persistent, and possibly evolutionarily significant new genes.     

A model of horizontal gene transfer and the bacterial phylogeny problem

How much horizontal gene transfer (HGT) between species influences bacterial phylogenomics is a controversial issue. This debate, however, lacks any quantitative assessment of the impact of HGT on phylogenies and of the ability of tree-building methods to cope with such events. I introduce a Markov model of genome evolution with HGT, accounting for the constraints on time -- an HGT event can only occur between concomitantly living species. This model is used to simulate multigene sequence data sets with or without HGT. The consequences of HGT on phylogenomic inference are analyzed and compared to other well-known phylogenetic artefacts. It is found that supertree methods are quite robust to HGT, keeping high levels of performance even when gene trees are largely incongruent with each other. Gene tree incongruence per se is not indicative of HGT. HGT, however, removes the (otherwise observed) positive relationship between sequence length and gene tree congruence to the estimated species tree. Surprisingly, when applied to a bacterial and a eukaryotic multigene data set, this criterion rejects the HGT hypothesis for the former, but not the latter data set.     

Studying plasmid horizontal transfer in situ: a critical review

This review deals with the prospective, experimental documentation of horizontal gene transfer (HGT) and its role in real-time, local adaptation. We have focused on plasmids and their function as an accessory and/or adaptive gene pool. Studies of the extent of HGT in natural environments have identified certain hot spots, and many of these involve biofilms. Biofilms are uniquely suited for HGT, as they sustain high bacterial density and metabolic activity, even in the harshest environments. Single-cell detection of donor, recipient and transconjugant bacteria in various natural environments, combined with individual-based mathematical models, has provided a new platform for HGT studies.     

Defence systems and horizontal gene transfer in bacteria

Horizontal gene transfer (HGT) is a fundamental process in prokaryotic evolution, contributing significantly to diversification and adaptation. HGT is typically facilitated by mobile genetic elements (MGEs), such as conjugative plasmids and phages, which often impose fitness costs on their hosts. However, a considerable number of bacterial genes are involved in defence mechanisms that limit the propagation of MGEs, suggesting they may actively restrict HGT. In our study, we investigated whether defence systems limit HGT by examining the relationship between the HGT rate and the presence of 73 defence systems across 12 bacterial species. We discovered that only six defence systems, three of which were different CRISPR-Cas subtypes, were associated with a reduced gene gain rate at the species evolution scale. Hosts of these defence systems tend to have a smaller pangenome size and fewer phage-related genes compared to genomes without these systems. This suggests that these defence mechanisms inhibit HGT by limiting prophage integration. We hypothesize that the restriction of HGT by defence systems is species-specific and depends on various ecological and genetic factors, including the burden of MGEs and the fitness effect of HGT in bacterial populations.     

Horizontal gene transfer in plants

Horizontal gene transfer (HGT) has played a major role in bacterial evolution and is fairly common in certain unicellular eukaryotes. However, the prevalence and importance of HGT in the evolution of multicellular eukaryotes remain unclear. Recent studies indicate that plant mitochondrial genomes are unusually active in HGT relative to all other organellar and nuclear genomes of multicellular eukaryotes. Although little about the mechanisms of plant HGT is known, several studies have implicated parasitic plants as both donors and recipients of mitochondrial genes. Most cases uncovered thus far have involved a single transferred gene per species; however, recent work has uncovered a case of massive HGT in Amborella trichopoda involving acquisition of at least a few dozen and probably hundreds of foreign mitochondrial genes. These foreign genes came from multiple donors, primarily eudicots and mosses. This review will examine the implications of such massive transfer, the potential mechanisms and consequences of plant-to-plant mitochondrial HGT in general, as well as the limited evidence for HGT in plant chloroplast and nuclear genomes.     

植物中的水平基因转移

水平基因转移是不通过生殖而进行的遗传物质交流, 在原核生物和单细胞真核生物的进化中起着重要作用。然而, 水平基因转移在多细胞真核生物之间的发生频率以及对多细胞真核生物进化的影响尚不明确。近期的一些研究显示, 水平基因转移在高等植物之间以及高等植物和其它生物之间普遍存在。该文将对高等植物中已发现的一些水平基因转移现象进行综述, 并尝试解析植物之间水平基因转移可能的机制及其重要意义。     

Phylogeny of γ‐proteobacteria: resolution of one branch of the universal tree?

The reconstruction of bacterial evolutionary relationships has proven to be a daunting task because variable mutation rates and horizontal gene transfer (HGT) among species can cause grave incongruities between phylogenetic trees based on single genes. Recently, a highly robust phylogenetic tree was constructed for 13 gamma-proteobacteria using the combined alignments of 205 conserved orthologous proteins.1 Only two proteins had incongruent tree topologies, which were attributed to HGT between Pseudomonas species and Vibrio cholerae or enterics. While the evolutionary relationships among these species appears to be resolved, further analysis suggests that HGT events with other bacterial partners likely occurred; this alters the implicit assumption of gamma-proteobacteria monophyly. Thus, any thorough reconstruction of bacterial evolution must not only choose a suitable set of molecular markers but also strive to reduce potential bias in the selection of species.     

The impact of horizontal gene transfer in shaping operons and protein interaction networks – direct evidence of preferential attachment

Background  

Despite the prevalence of horizontal gene transfer (HGT) in bacteria, to this date there were few studies on HGT in the context of gene expression, operons and protein-protein interactions. Using the recently available data set on the E. coli protein-protein interaction network, we sought to explore the impact of HGT on genome structure and protein networks.     

Natural taxonomy in light of horizontal gene transfer

We discuss the impact of horizontal gene transfer (HGT) on phylogenetic reconstruction and taxonomy. We review the power of HGT as a creative force in assembling new metabolic pathways, and we discuss the impact that HGT has on phylogenetic reconstruction. On one hand, shared derived characters are created through transferred genes that persist in the recipient lineage, either because they were adaptive in the recipient lineage or because they resulted in a functional replacement. On the other hand, taxonomic patterns in microbial phylogenies might also be created through biased gene transfer. The agreement between different molecular phylogenies has encouraged interpretation of the consensus signal as reflecting organismal history or as the tree of cell divisions; however, to date the extent to which the consensus reflects shared organismal ancestry and to which it reflects highways of gene sharing and biased gene transfer remains an open question. Preferential patterns of gene exchange act as a homogenizing force in creating and maintaining microbial groups, generating taxonomic patterns that are indistinguishable to those created by shared ancestry. To understand the evolution of higher bacterial taxonomic units, concepts usually applied in population genetics need to be applied.     

Efficient parsimony-based methods for phylogenetic network reconstruction

MOTIVATION: Phylogenies--the evolutionary histories of groups of organisms-play a major role in representing relationships among biological entities. Although many biological processes can be effectively modeled as tree-like relationships, others, such as hybrid speciation and horizontal gene transfer (HGT), result in networks, rather than trees, of relationships. Hybrid speciation is a significant evolutionary mechanism in plants, fish and other groups of species. HGT plays a major role in bacterial genome diversification and is a significant mechanism by which bacteria develop resistance to antibiotics. Maximum parsimony is one of the most commonly used criteria for phylogenetic tree inference. Roughly speaking, inference based on this criterion seeks the tree that minimizes the amount of evolution. In 1990, Jotun Hein proposed using this criterion for inferring the evolution of sequences subject to recombination. Preliminary results on small synthetic datasets. Nakhleh et al. (2005) demonstrated the criterion's application to phylogenetic network reconstruction in general and HGT detection in particular. However, the naive algorithms used by the authors are inapplicable to large datasets due to their demanding computational requirements. Further, no rigorous theoretical analysis of computing the criterion was given, nor was it tested on biological data. RESULTS: In the present work we prove that the problem of scoring the parsimony of a phylogenetic network is NP-hard and provide an improved fixed parameter tractable algorithm for it. Further, we devise efficient heuristics for parsimony-based reconstruction of phylogenetic networks. We test our methods on both synthetic and biological data (rbcL gene in bacteria) and obtain very promising results.     

Monitoring and modeling horizontal gene transfer

Monitoring efforts have failed to identify horizontal gene transfer (HGT) events occurring from transgenic plants into bacterial communities in soil or intestinal environments. The lack of such observations is frequently cited in biosafety literature and by regulatory risk assessment. Our analysis of the sensitivity of current monitoring efforts shows that studies to date have examined potential HGT events occurring in less than 2 g of sample material, when combined. Moreover, a population genetic model predicts that rare bacterial transformants acquiring transgenes require years of growth to out-compete wild-type bacteria. Time of sampling is there-fore crucial to the useful implementation of monitoring. A population genetic approach is advocated for elucidating the necessary sample sizes and times of sampling for monitoring HGT into large bacterial populations. Major changes in current monitoring approaches are needed, including explicit consideration of the population size of exposed bacteria, the bacterial generation time, the strength of selection acting on the transgene-carrying bacteria, and the sample size necessary to verify or falsify the HGT hypotheses tested.     

Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches

Horizontal genetic transfer (HGT) has played an important role in bacterial evolution at least since the origins of the bacterial divisions, and HGT still facilitates the origins of bacterial diversity, including diversity based on antibiotic resistance. Adaptive HGT is aided by unique features of genetic exchange in bacteria such as the promiscuity of genetic exchange and the shortness of segments transferred. Genetic exchange rates are limited by the genetic and ecological similarity of organisms. Adaptive transfer of genes is limited to those that can be transferred as a functional unit, provide a niche-transcending adaptation, and are compatible with the architecture and physiology of other organisms. Horizontally transferred adaptations may bring about fitness costs, and natural selection may ameliorate these costs. The origins of ecological diversity can be analyzed by comparing the genomes of recently divergent, ecologically distinct populations, which can be discovered as sequence clusters. Such genome comparisons demonstrate the importance of HGT in ecological diversification. Newly divergent populations cannot be discovered as sequence clusters when their ecological differences are coded by plasmids, as is often the case for antibiotic resistance; the discovery of such populations requires a screen for plasmid-coded functions. This paper reviews the features of bacterial genetics that allow HGT, the similarities between organisms that foster HGT between them, the limits to the kinds of adaptations that can be transferred, and amelioration of fitness costs associated with HGT; the paper also reviews approaches to discover the origins of new, ecologically distinct bacterial populations and the role that HGT plays in their founding.     

Speciation in <Emphasis Type="Italic">Chlamydia</Emphasis>: Genomewide Phylogenetic Analyses Identified a Reliable Set of Acquired Genes

Horizontal gene transfer (HGT), a process through which genomes acquire sequences from distantly related organisms, is believed to be a major source of genetic diversity in bacteria. A central question concerning the impact of HGT on bacterial genome evolution is the proportion of horizontally transferred sequences within genomes. This issue, however, remains unresolved because the various methods developed to detect potential HGT events identify different sets of genes. The present-day consensus is that phylogenetic analysis of individual genes is still the most objective and accurate approach for determining the occurrence and directionality of HGT. Here we present a genome-scale phylogenetic analysis of protein-encoding genes from five closely related Chlamydia, identifying a reliable set of sequences that have arisen via HGT since the divergence of the Chlamydia lineage. According to our knowledge, this is the first systematic phylogenetic inference-based attempt to establish a reliable set of acquired genes in a bacterial genome. Although Chlamydia are obligate intracellular parasites of higher eukaryotes, and thus suspected to be isolated from HGT more than the free-living species, our results show that their diversification has involved the introduction of foreign sequences into their genome. Furthermore, we also identified a complete set of genes that have undergone deletion, duplication, or rearrangement during this evolutionary period leading to the radiation of Chlamydia species. Our analysis may provide a deeper insight into how these medically important pathogens emerged and evolved from a common ancestor.     

Phylogenetic comparison of metabolic capacities of organisms at genome level

Horizontal gene transfer (HGT) has been shown to widely spread in organisms by comparative genomic studies. However, its effect on the phylogenetic relationship of organisms, especially at a system level of different cellular functions, is still not well understood. In this work, we have constructed phylogenetic trees based on the enzyme, reaction, and gene contents of metabolic networks reconstructed from annotated genome information of 82 sequenced organisms. Results from different phylogenetic distance definitions and based on three different functional subsystems (i.e., metabolism, cellular processes, information storage and processing) were compared. Results based on the three different functional subsystems give different pictures on the phylogenetic relationship of organisms, reflecting the different extents of HGT in the different functional systems. In general, horizontal transfer is prevailing in genes for metabolism, but less in genes for information processing. Nevertheless, the major results of metabolic network-based phylogenetic trees are in good agreement with the tree based on 16S rRNA and genome trees, confirming the three domain classification and the close relationship between eukaryotes and archaea at the level of metabolic networks. These results strongly support the hypothesis that although HGT is widely distributed, it is nevertheless constrained by certain pre-existing metabolic organization principle(s) during the evolution. Further research is needed to identify the organization principle and constraints of metabolic network on HGT which have large impacts on understanding the evolution of life and in purposefully manipulating cellular metabolism.     

Environmental Factors Influencing Gene Transfer Agent (GTA) Mediated Transduction in the Subtropical Ocean

Microbial genomic sequence analyses have indicated widespread horizontal gene transfer (HGT). However, an adequate mechanism accounting for the ubiquity of HGT has been lacking. Recently, high frequencies of interspecific gene transfer have been documented, catalyzed by Gene Transfer Agents (GTAs) of marine α-Proteobacteria. It has been proposed that the presence of bacterial genes in highly purified viral metagenomes may be due to GTAs. However, factors influencing GTA-mediated gene transfer in the environment have not yet been determined. Several genomically sequenced strains containing complete GTA sequences similar to Rhodobacter capsulatus (RcGTA, type strain) were screened to ascertain if they produced putative GTAs, and at what abundance. Five of nine marine strains screened to date spontaneously produced virus-like particles (VLP's) in stationary phase. Three of these strains have demonstrated gene transfer activity, two of which were documented by this lab. These two strains Roseovarius nubinhibens ISM and Nitratireductor 44B9s, were utilized to produce GTAs designated RnGTA and NrGTA and gene transfer activity was verified in culture. Cell-free preparations of purified RnGTA and NrGTA particles from marked donor strains were incubated with natural microbial assemblages to determine the level of GTA-mediated gene transfer. In conjunction, several ambient environmental parameters were measured including lysogeny indicated by prophage induction. GTA production in culture systems indicated that approximately half of the strains produced GTA-like particles and maximal GTA counts ranged from 10-30% of host abundance. Modeling of GTA-mediated gene transfer frequencies in natural samples, along with other measured environmental variables, indicated a strong relationship between GTA mediated gene transfer and the combined factors of salinity, multiplicity of infection (MOI) and ambient bacterial abundance. These results indicate that GTA-mediated HGT in the marine environment with the strains examined is favored during times of elevated bacterial and GTA abundance as well as in areas of higher salinity.     

Mobility of the Yersinia High-Pathogenicity Island (HPI): transfer mechanisms of pathogenicity islands (PAIS) revisited (a review)

Horizontal gene transfer (HGT) plays a key role in the evolution of bacterial pathogens. The exchange of genetic material supplies prokaryotes with several fitness traits enhancing their adaptive response to environmental changes. Pathogenicity islands (PAIs) represent an important and in most cases already immobilized subset of the different vehicles for HGT. Encoding several virulence factors PAls represent a major contribution to bacterial pathogenicity. Nonetheless, the transfer mechanisms of PAIs still remain elusive. We summarise the currently available data regarding the major ways of genetic mobilisation with a focus on the transfer of the Yersinia High-Pathogenicity Island (HPI).