Characterizing Scales of Genetic Recombination and Antibiotic Resistance in Pathogenic Bacteria Using Topological Data Analysis

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 reservoir for antibiotic resistance genes.Comment: 12 pages, 6 figures. To appear in AMT 2014 Special Session on Advanced Methods of Interactive Data Mining for Personalized Medicin

Patterns of prokaryotic lateral gene transfers affecting parasitic microbial eukaryotes

Background: The influence of lateral gene transfer on gene origins and biology in eukaryotes is poorly understood compared with those of prokaryotes. A number of independent investigations focusing on specific genes, individual genomes, or specific functional categories from various eukaryotes have indicated that lateral gene transfer does indeed affect eukaryotic genomes. However, the lack of common methodology and criteria in these studies makes it difficult to assess the general importance and influence of lateral gene transfer on eukaryotic genome evolution. Results: We used a phylogenomic approach to systematically investigate lateral gene transfer affecting the proteomes of thirteen, mainly parasitic, microbial eukaryotes, representing four of the six eukaryotic super-groups. All of the genomes investigated have been significantly affected by prokaryote-to-eukaryote lateral gene transfers, dramatically affecting the enzymes of core pathways, particularly amino acid and sugar metabolism, but also providing new genes of potential adaptive significance in the life of parasites. A broad range of prokaryotic donors is involved in such transfers, but there is clear and significant enrichment for bacterial groups that share the same habitats, including the human microbiota, as the parasites investigated. Conclusions: Our data show that ecology and lifestyle strongly influence gene origins and opportunities for gene transfer and reveal that, although the outlines of the core eukaryotic metabolism are conserved among lineages, the genes making up those pathways can have very different origins in different eukaryotes. Thus, from the perspective of the effects of lateral gene transfer on individual gene ancestries in different lineages, eukaryotic metabolism appears to be chimeric

The largest reservoir of mitochondrial introns is a relic of an ancestral split gene

In eukaryotes, introns are located in nuclear and organelle genes from several kingdoms (ref. 1-4). Large introns (0.1 to 5 kbp) are frequent in mitochondrial genomes of plant and fungi (ref. 1,5) but scarce in Metazoa, despite these organisms are grouped with fungi among Opisthokonts. Introns are classified in two main groups (I and II) according to their RNA secondary structure involved in the intron self-splicing mechanism (ref. 5,6). Most of the group I introns carry a "Homing Endonuclease Gene" (ref. 7-9) encoding a DNA endonuclease acting in the transfer and site specific integration "homing") and allowing the intron spreading and gain after lateral transfer even between species from different kingdoms (ref. 10,11). Opposite to this "late intron" paradigm, the "early intron" theory indicates that introns, which would have been abundant in the ancestral genes, would mainly evolve by loss (ref. 12,13).

Here we report the sequence of the cox1 gene of the button mushroom _Agaricus bisporus_, the most worldwide cultivated mushroom. This gene is both the longest mitochondrial gene (29,902 nt) and the largest Group I intron reservoir reported to date. An analysis of the group I introns available in _cox1_ genes shows that they are ancestral mobile genetic elements, whose frequent events of loss (according to the "late theory") and gain by lateral transfer ("early theory") must be combined to explain their wide and patchy distribution extending on several kingdoms. This allows the conciliation of the "early" and "late intron" paradigms, which are still matters of much debate (ref. 14,15). The overview of the intron distribution indicates that they evolve towards elimination. In such a landscape of eroded and lost intron sequences, the _A. bisporus_ largest intron reservoir, by its singular dynamics of intron keeping and catching, constitutes the most fitted relic of an early split gene

Inferring Species Trees from Incongruent Multi-Copy Gene Trees Using the Robinson-Foulds Distance

We present a new method for inferring species trees from multi-copy gene trees. Our method is based on a generalization of the Robinson-Foulds (RF) distance to multi-labeled trees (mul-trees), i.e., gene trees in which multiple leaves can have the same label. Unlike most previous phylogenetic methods using gene trees, this method does not assume that gene tree incongruence is caused by a single, specific biological process, such as gene duplication and loss, deep coalescence, or lateral gene transfer. We prove that it is NP-hard to compute the RF distance between two mul-trees, but it is easy to calculate the generalized RF distance between a mul-tree and a singly-labeled tree. Motivated by this observation, we formulate the RF supertree problem for mul-trees (MulRF), which takes a collection of mul-trees and constructs a species tree that minimizes the total RF distance from the input mul-trees. We present a fast heuristic algorithm for the MulRF supertree problem. Simulation experiments demonstrate that the MulRF method produces more accurate species trees than gene tree parsimony methods when incongruence is caused by gene tree error, duplications and losses, and/or lateral gene transfer. Furthermore, the MulRF heuristic runs quickly on data sets containing hundreds of trees with up to a hundred taxa.Comment: 16 pages, 11 figure

Genome-scale phylogenetic analysis finds extensive gene transfer among Fungi

Although the role of lateral gene transfer is well recognized in the evolution of bacteria, it is generally assumed that it has had less influence among eukaryotes. To explore this hypothesis we compare the dynamics of genome evolution in two groups of organisms: Cyanobacteria and Fungi. Ancestral genomes are inferred in both clades using two types of methods. First, Count, a gene tree unaware method that models gene duplications, gains and losses to explain the observed numbers of genes present in a genome. Second, ALE, a more recent gene tree-aware method that reconciles gene trees with a species tree using a model of gene duplication, loss, and transfer. We compare their merits and their ability to quantify the role of transfers, and assess the impact of taxonomic sampling on their inferences. We present what we believe is compelling evidence that gene transfer plays a significant role in the evolution of Fungi

Unconventional lateral gene transfer in extreme thermophilic bacteria

Conjugation and natural competence are two major mechanisms that explain the acquisition of foreign genes throughout bacterial evolution. In recent decades, several studies in model organisms have revealed in great detail the steps involved in such processes. The findings support the idea that the major basis of these mechanisms is essentially similar in all bacteria. However, recent work has pinpointed the existence of new, evolutionarily different processes underlying lateral gene transfer. In Thermus thermophilus HB27, at least 16 proteins are required for the activity of one of the most efficient natural competence systems known so far. Many of those proteins have no similarities to proteins involved in natural competence in other well-known models. This unusual competence system is conserved, in association with the chromosome, in all other Thermus spp. genomes so far available, it being functional even in strains from isolated environments, such as deep mines. Conjugation is also possible among Thermus spp. Homologues to proteins implicated in conjugation in model bacteria are encoded in the genome of a recently sequenced strain of Thermus thermophilus and shared by other members of the genus. Nevertheless, processive DNA transfer in the absence of a functional natural competence system in strains in which no conjugation homologous genes can be found hints at the existence of an additional and unconventional conjugation mechanism in these bacteriaThis work was supported by grant BIO2010-18875 from the Spanish Ministry of Science and Innovation. An institutional grant from Ramón Areces Foundation to CBMSO is acknowledged. CEC holds a Juan de la Cierva postdoctoral contract from the Spanish Ministry of Science and Innovation. CB and LA are founded by FPI and JAE fellowships from the Ministry of Education and the Spanish National Research Council (CSIC), respectivel

Evidence for the intense exchange of MazG in marine cyanophages by horizontal gene transfer

Background: S-PM2 is a phage capable of infecting strains of unicellular cyanobacteria belonging to the genus Synechococcus. S-PM2, like other myoviruses infecting marine cyanobacteria, encodes a number of bacterial-like genes. Amongst these genes is one encoding a MazG homologue that is hypothesized to be involved in the adaption of the infected host for production of progeny phage. Methodology/Principal Findings: This study focuses on establishing the occurrence of mazG homologues in other cyanophages isolated from different oceanic locations. Degenerate PCR primers were designed using the mazG gene of S-PM2. The mazG gene was found to be widely distributed and highly conserved among Synechococcus myoviruses and podoviruses from diverse oceanic provinces. Conclusions/Significance: This study provides evidence of a globally connected cyanophage gene pool, the cyanophage mazG gene having a small effective population size indicative of rapid lateral gene transfer despite being present in a substantial fraction of cyanophage. The Prochlorococcus and Synechococcus phage mazG genes do not cluster with the host mazG gene, suggesting that their primary hosts are not the source of the mazG gene

Quantifying the Extent of Lateral Gene Transfer Required to Avert a `Genome of Eden'

The complex pattern of presence and absence of many genes across different species provides tantalising clues as to how genes evolved through the processes of gene genesis, gene loss and lateral gene transfer (LGT). The extent of LGT, particularly in prokaryotes, and its implications for creating a `network of life' rather than a `tree of life' is controversial. In this paper, we formally model the problem of quantifying LGT, and provide exact mathematical bounds, and new computational results. In particular, we investigate the computational complexity of quantifying the extent of LGT under the simple models of gene genesis, loss and transfer on which a recent heuristic analysis of biological data relied. Our approach takes advantage of a relationship between LGT optimization and graph-theoretical concepts such as tree width and network flow