Molecular musings in microbial ecology and evolution

<p>Abstract</p> <p/> <p>A few major discoveries have influenced how ecologists and evolutionists study microbes. Here, in the format of an interview, we answer questions that directly relate to how these discoveries are perceived in these two branches of microbiology, and how they have impacted on both scientific thinking and methodology.</p> <p>The first question is "<it>What has been the influence of the 'Universal Tree of Life' based on molecular markers?" </it>For evolutionists, the tree was a tool to understand the past of known (cultured) organisms, mapping the invention of various physiologies on the evolutionary history of microbes. For ecologists the tree was a guide to discover the current diversity of unknown (uncultured) organisms, without much knowledge of their physiology.</p> <p>The second question we ask is "<it>What was the impact of discovering frequent lateral gene transfer among microbes?" </it>In evolutionary microbiology, frequent lateral gene transfer (LGT) made a simple description of relationships between organisms impossible, and for microbial ecologists, functions could not be easily linked to specific genotypes. Both fields initially resisted LGT, but methods or topics of inquiry were eventually changed in one to incorporate LGT in its theoretical models (evolution) and in the other to achieve its goals despite that phenomenon (ecology).</p> <p>The third and last question we ask is "<it>What are the implications of the unexpected extent of diversity?" </it>The variation in the extent of diversity between organisms invalidated the universality of species definitions based on molecular criteria, a major obstacle to the adaptation of models developed for the study of macroscopic eukaryotes to evolutionary microbiology. This issue has not overtly affected microbial ecology, as it had already abandoned species in favor of the more flexible operational taxonomic units. This field is nonetheless moving away from traditional methods to measure diversity, as they do not provide enough resolution to uncover what lies below the species level.</p> <p>The answers of the evolutionary microbiologist and microbial ecologist to these three questions illustrate differences in their theoretical frameworks. These differences mean that both fields can react quite distinctly to the same discovery, incorporating it with more or less difficulty in their scientific practice.</p> <p>Reviewers</p> <p>This article was reviewed by W. Ford Doolittle, Eugene V. Koonin and Maureen A. O'Malley.</p

Refuting phylogenetic relationships

BACKGROUND: Phylogenetic methods are philosophically grounded, and so can be philosophically biased in ways that limit explanatory power. This constitutes an important methodologic dimension not often taken into account. Here we address this dimension in the context of concatenation approaches to phylogeny. RESULTS: We discuss some of the limits of a methodology restricted to verificationism, the philosophy on which gene concatenation practices generally rely. As an alternative, we describe a software which identifies and focuses on impossible or refuted relationships, through a simple analysis of bootstrap bipartitions, followed by multivariate statistical analyses. We show how refuting phylogenetic relationships could in principle facilitate systematics. We also apply our method to the study of two complex phylogenies: the phylogeny of the archaea and the phylogeny of the core of genes shared by all life forms. While many groups are rejected, our results left open a possible proximity of N. equitans and the Methanopyrales, of the Archaea and the Cyanobacteria, and as well the possible grouping of the Methanobacteriales/Methanoccocales and Thermosplasmatales, of the Spirochaetes and the Actinobacteria and of the Proteobacteria and firmicutes. CONCLUSION: It is sometimes easier (and preferable) to decide which species do not group together than which ones do. When possible topologies are limited, identifying local relationships that are rejected may be a useful alternative to classical concatenation approaches aiming to find a globally resolved tree on the basis of weak phylogenetic markers. REVIEWERS: This article was reviewed by Mark Ragan, Eugene V Koonin and J Peter Gogarten

Emergence, ecology and dispersal of the pandemic generating Vibrio cholerae lineage

Although cholera is an ancient disease that first arose at least half a millennium ago, it remains a major health threatglobally. Its pandemic form is caused by strains from a single lineage of the bacterium Vibrio cholerae. The ancestor of this lineageharbored several distinctive characteristics, the most notable being the O1 antigen polysaccharide. This lineage generatedtwo biotypes, first Classical, responsible for six pandemics, and later El Tor, responsible for the seventh and ongoing pandemic.Just as El Tor replaced Classical as the main cause of outbreaks in the last fifty years, several variants of El Tor have evolved anddisplaced their predecessors worldwide. Understanding the ecology, evolution and dispersal of pandemic V. cholerae is centralto studying this complex disease with environmental reservoirs. Here, we present recent advancements of our knowledge on theemergence and spread of the pandemic generating lineage of V. cholerae in the light of established eco-evolutionary observations.Specific ecological interactions shape seasonal cholera, playing a role in the abundance and distribution of its causative agent.Both species-specific and lineage-specific genetic determinants play a role in the ability of V. cholerae strains to cause pandemicswith seasonal outbreaks, having evolved gradually over centuries. On the basis of the current understanding, we outline futurethreats and changes in biogeographical and genomic-based investigation strategies to combat this global problem

The 2010 cholera outbreak in Haiti: How science solved a controversy

The article focuses on the genetic basis of the spread of cholera in Haiti which clarifies both the climatic and human transmission hypotheses explaining the origin of the disease after the January 12, 2010 earthquake. Topics include the role of the nonpathogenic Vibrio cholerae in cholera, studies supporting the human transmission hypothesis, and molecular study on the origin of Vibrio cholerae in the country. The use of genome sequencing as a tool for molecular epidemiology is considered

Integration of a laterally acquired gene into a cell network important for growth in a strain of Vibrio rotiferianus

<p>Abstract</p> <p>Background</p> <p>Lateral Gene Transfer (LGT) is a major contributor to bacterial evolution and up to 25% of a bacterium's genome may have been acquired by this process over evolutionary periods of time. Successful LGT requires both the physical transfer of DNA and its successful incorporation into the host cell. One system that contributes to this latter step by site-specific recombination is the integron. Integrons are found in many diverse bacterial Genera and is a genetic system ubiquitous in vibrios that captures mobile DNA at a dedicated site. The presence of integron-associated genes, contained within units of mobile DNA called gene cassettes makes up a substantial component of the vibrio genome (1-3%). Little is known about the role of this system since the vast majority of genes in vibrio arrays are highly novel and functions cannot be ascribed. It is generally regarded that strain-specific mobile genes cannot be readily integrated into the cellular machinery since any perturbation of core metabolism is likely to result in a loss of fitness.</p> <p>Results</p> <p>In this study, at least one mobile gene contained within the <it>Vibrio rotiferianus </it>strain DAT722, but lacking close relatives elsewhere, is shown to greatly reduce host fitness when deleted and tested in growth assays. The precise role of the mobile gene product is unknown but impacts on the regulation of outermembrane porins. This demonstrates that strain specific laterally acquired mobile DNA can be integrated rapidly into bacterial networks such that it becomes advantageous for survival and adaptation in changing environments.</p> <p>Conclusions</p> <p>Mobile genes that are highly strain specific are generally believed to act in isolation. This is because perturbation of existing cell machinery by the acquisition of a new gene by LGT is highly likely to lower fitness. In contrast, we show here that at least one mobile gene, apparently unique to a strain, encodes a product that has integrated into central cellular metabolic processes such that it greatly lowers fitness when lost under those conditions likely to be commonly encountered for the free living cell. This has ramifications for our understanding of the role mobile gene encoded products play in the cell from a systems biology perspective.</p

Land use history (1840–2005) and physiography as determinants of southern boreal forests

Land use history has altered natural disturbance dynamics, causing widespread modifications of the earth's forests. The aim of this study is to reconstruct a regional, spatially-explicit, fire and logging history for a large southern boreal forest landscape (6,050 km2) of eastern Canada. We then examined the long-term influence of land use history, fires, and physiographical gradients on the area's disturbances regimes, present-day age structure and tree species composition. Spatially-explicit fire (1820-2005) and logging (1900-2005) histories were reconstructed from forestry maps, terrestrial forest inventories and historical records (local newspapers, travel notes, regional historical reviews). Logistic regression was used to model the occurrence of major boreal tree species at the regional scale, in relation to their disturbance history and physiographical variables. The interplay of elevation and fire history was found to explain a large part of the present-day distribution of the four species studied. We conclude that human-induced fires following the colonization activities of the nineteenth and twentieth centuries have increased fire frequency and the dominance of fire-adapted species at lower elevations. At higher elevations, the low historical fire frequency has fostered the dominance of fire-sensitive species. Twentieth-century forestry practices and escaped settlement fires have generated a forest landscape dominated by younger forest habitats than in presettlement times. The expected increase of wildfire activity in North America's eastern boreal forest, in conjunction with continued forest management, could have significant consequences on the resilience of boreal forests

Rational Design of an Epitope-Based Hepatitis C Virus Vaccine

Despite improving treatment methods and therapeutic options, hepatitis C virus (HCV) remains a major global disease burden, and a vaccine would help greatly in reducing its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response, thus a vaccine must elicit an immune response toward conserved, functionally important epitopes. Using structural data of the broadly neutralizing antibody HCV1 in complex with a conserved linear epitope from the HCV E2 protein (aa 412-423, referred to as epitope I or domain E), we performed structure-based design to generate vaccine immunogens to induce antibody responses to this epitope. Designs selected for immunological characterization included a stabilized minimal epitope structure based on a defensin protein, as well as a bivalent vaccine featuring two copies of epitope I on the E2 surface. In vivo studies confirmed that these designs successfully generated robust antibody responses to this epitope, and sera from vaccinated mice neutralized HCV. In addition to presenting several effective HCV vaccine immunogens, this study demonstrates that induction of neutralizing anti-HCV antibodies is possible using an epitope-based vaccine, providing the basis for further efforts in structure-based vaccine design to target this and other critical epitopes of HCV

Targeted Mutagenesis of a Therapeutic Human Monoclonal IgG1 Antibody Prevents Gelation at High Concentrations

A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association, formation of a semi-solid gel or “gelation”. Therapeutic monoclonal antibody C4 was isolated from human B cells based on its strong potency in neutralizing bacterial toxin in animal models. The purified antibody possessed the unusual property of forming a firm, opaque white gel when it was formulated at concentrations \u3e40 mg/mL and the temperature wa

Positive effects of projected climate change on post-disturbance forest regrowth rates in northeastern North American boreal forests

Forest anthropogenic and natural stand-replacing disturbances are increasing worldwide due to global change. Many uncertainties regarding the regeneration and growth of these young forests remain within the context of changing climate. In this study, we investigate the effects of climate, tree species composition, and other landscape-scale environmental variables upon boreal forest regrowth following clearcut logging in eastern Canada. Our main objective was to predict the effects of future climate changes upon post-logging forest height regrowth at a subcontinental scale using high spatial resolution remote sensing data. We modeled forest canopy height (estimated from airborne laser scanning [LiDAR] data over 20 m resolution virtual plots) as a function of time elapsed since the last clearcut along with climate (i.e. temperature and moisture), tree species composition, and other environmental variables (e.g. topography and soil hydrology). Once trained and validated with ∼240 000 plots, the model that was developed in this study was used to predict potential post-logging canopy height regrowth at 20 m resolution across a 240 000 km 2 area following scenarios depicting a range of projected changes in temperature and moisture across the region for 2041–2070. Our results predict an overall beneficial, but limited effect of projected climate changes upon forest regrowth rates in our study area. Stimulatory effects of projected climate change were more pronounced for conifer forests, with growth rates increasing between +5% and +50% over the study area, while mixed and broadleaved forests recorded changes that mostly ranged from −5% to +35%. Predicted increased regrowth rates were mainly associated with increased temperature, while changes in climate moisture had a minor effect. We conclude that such growth gains could partially compensate for the inevitable increase in natural disturbances but should not allow any increase in harvested volumes