Bioinformatics of genome evolution: from ancestral to modern metabolism

Bioinformatics, that is the interdisciplinary field that blends computer science and biostatistics with biological and biomedical sciences, is expected to gain a central role in next feature. Indeed, it has now affected several fields of biology, providing crucial hints for the understanding of biological systems and also allowing a more accurate design of wet lab experiments. In this work, the analysis of sequence data has be used in different fields, such as evolution (e.g. the assembly and evolution of metabolism), infections control (e.g. the horizontal flow of antibiotic resistance), ecology (bacterial bioremediation)

On the origin and evolution of biosynthetic pathways: integrating microarray data with structure and organization of the Common Pathway genes

Background: The lysine, threonine, and methionine biosynthetic pathways share the three initial enzymatic steps, which are referred to as the Common Pathway (CP). In Escherichia coli three different aspartokinases (AKI, AKII, AKIII, the products of thrA, metL and lysC, respectively) can perform the first step of the CP. Moreover, two of them (AKI and AKII) are bifunctional, carrying also homoserine dehydrogenasic activity (hom product). The second step of the CP is catalyzed by a single aspartate semialdehyde dehydrogenase (ASDH, the product of asd). Thus, in the CP of E. coli while a single copy of ASDH performs the same reaction for three different metabolic routes, three different AKs perfom a unique step. Why and how such a situation did emerge and maintain? How is it correlated to the different regulatory mechanisms acting on these genes? The aim of this work was to trace the evolutionary pathway leading to the extant scenario in proteobacteria. Results: The analysis of the structure, organization, phylogeny, and distribution of ask and hom genes revealed that the presence of multiple copies of these genes and their fusion events are restricted to the gamma-subdivision of proteobacteria. This allowed us to depict a model to explain the evolution of ask and hom according to which the fused genes are the outcome of a cascade of gene duplication and fusion events that can be traced in the ancestor of gamma-proteobacteria. Moreover, the appearance of fused genes paralleled the assembly of operons of different sizes, suggesting a strong correlation between the structure and organization of these genes. A statistic analysis of microarray data retrieved from experiments carried out on E. coli and Pseudomonas aeruginosa was also performed. Conclusion: The integration of data concerning gene structure, organization, phylogeny, distribution, and microarray experiments allowed us to depict a model for the evolution of ask and hom genes in proteobacteria and to suggest a biological significance for the extant scenario

Perspectives and Challenges in Microbial Communities Metabolic Modeling

Bacteria have evolved to efficiently interact each other, forming complex entities known as microbial communities. These “super-organisms” play a central role in maintaining the health of their eukaryotic hosts and in the cycling of elements like carbon and nitrogen. However, despite their crucial importance, the mechanisms that influence the functioning of microbial communities and their relationship with environmental perturbations are obscure. The study of microbial communities was boosted by tremendous advances in sequencing technologies, and in particular by the possibility to determine genomic sequences of bacteria directly from environmental samples. Indeed, with the advent of metagenomics, it has become possible to investigate, on a previously unparalleled scale, the taxonomical composition and the functional genetic elements present in a specific community. Notwithstanding, the metagenomic approach per se suffers some limitations, among which the impossibility of modeling molecular-level (e.g., metabolic) interactions occurring between community members, as well as their effects on the overall stability of the entire system. The family of constraint-based methods, such as flux balance analysis, has been fruitfully used to translate genome sequences in predictive, genome-scale modeling platforms. Although these techniques have been initially developed for analyzing single, well-known model organisms, their recent improvements allowed engaging in multi-organism in silico analyses characterized by a considerable predictive capability. In the face of these advances, here we focus on providing an overview of the possibilities and challenges related to the modeling of metabolic interactions within a bacterial community, discussing the feasibility and the perspectives of this kind of analysis in the (near) future

The role of gene fusions in the evolution of metabolic pathways: the histidine biosynthesis case

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Histidine biosynthesis is one of the best characterized anabolic pathways. There is a large body of genetic and biochemical information available, including operon structure, gene expression, and increasingly larger sequence databases. For over forty years this pathway has been the subject of extensive studies, mainly in Escherichia coli and Salmonella enterica, in both of which details of histidine biosynthesis appear to be identical. In these two enterobacteria the pathway is unbranched, includes a number of unusual reactions, and consists of nine intermediates; his genes are arranged in a compact operon (hisGDC [NB]HAF [IE]), with three of them (hisNB, hisD and hisIE) coding for bifunctional enzymes. We performed a detailed analysis of his gene fusions in available genomes to understand the role of gene fusions in shaping this pathway. Results The analysis of HisA structures revealed that several gene elongation events are at the root of this protein family: internal duplication have been identified by structural superposition of the modules composing the TIM-barrel protein. Several his gene fusions happened in distinct taxonomic lineages; hisNB originated within γ-proteobacteria and after its appearance it was transferred to Campylobacter species (ε-proteobacteria) and to some Bacteria belonging to the CFB group. The transfer involved the entire his operon. The hisIE gene fusion was found in several taxonomic lineages and our results suggest that it probably happened several times in distinct lineages. Gene fusions involving hisIE and hisD genes (HIS4) and hisH and hisF genes (HIS7) took place in the Eukarya domain; the latter has been transferred to some δ-proteobacteria. Conclusion Gene duplication is the most widely known mechanism responsible for the origin and evolution of metabolic pathways; however, several other mechanisms might concur in the process of pathway assembly and gene fusion appeared to be one of the most important and common

Large-Scale Analysis of Plasmid Relationships through Gene-Sharing Networks

Plasmids are vessels of genetic exchange in microbial communities. They are known to transfer between different host organisms and acquire diverse genetic elements from chromosomes and/or other plasmids. Therefore, they constitute an important element in microbial evolution by rapidly disseminating various genetic properties among different communities. A paradigmatic example of this is the dissemination of antibiotic resistance (AR) genes that has resulted in the emergence of multiresistant pathogenic bacterial strains. To globally analyze the evolutionary dynamics of plasmids, we built a large graph in which 2,343 plasmids (nodes) are connected according to the proteins shared by each other. The analysis of this gene-sharing network revealed an overall coherence between network clustering and the phylogenetic classes of the corresponding microorganisms, likely resulting from genetic barriers to horizontal gene transfer between distant phylogenetic groups. Habitat was not a crucial factor in clustering as plasmids from organisms inhabiting different environments were often found embedded in the same cluster. Analyses of network metrics revealed a statistically significant correlation between plasmid mobility and their centrality within the network, providing support to the observation that mobile plasmids are particularly important in spreading genes in microbial communities. Finally, our study reveals an extensive (and previously undescribed) sharing of AR genes between Actinobacteria and Gammaproteobacteria, suggesting that the former might represent an important reservoir of AR genes for the latter

A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land

<p>Abstract</p> <p>Background</p> <p>The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified.</p> <p>Results</p> <p>We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL), which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PAL <it>via </it>horizontal gene transfer (HGT) during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments.</p> <p>Conclusion</p> <p>Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments) suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV.</p> <p>Reviewers</p> <p>This article was reviewed by Purificación López-García, Janet Siefert, and Eugene Koonin.</p

The role of gene fusions in the evolution of metabolic pathways: the histidine biosynthesis case.

BACKGROUND: Histidine biosynthesis is one of the best characterized anabolic pathways. There is a large body of genetic and biochemical information available, including operon structure, gene expression, and increasingly larger sequence databases. For over forty years this pathway has been the subject of extensive studies, mainly in Escherichia coli and Salmonella enterica, in both of which details of histidine biosynthesis appear to be identical. In these two enterobacteria the pathway is unbranched, includes a number of unusual reactions, and consists of nine intermediates; his genes are arranged in a compact operon (hisGDC [NB]HAF [IE]), with three of them (hisNB, hisD and hisIE) coding for bifunctional enzymes. We performed a detailed analysis of his gene fusions in available genomes to understand the role of gene fusions in shaping this pathway. RESULTS: The analysis of HisA structures revealed that several gene elongation events are at the root of this protein family: internal duplication have been identified by structural superposition of the modules composing the TIM-barrel protein. Several his gene fusions happened in distinct taxonomic lineages; hisNB originated within gamma-proteobacteria and after its appearance it was transferred to Campylobacter species (epsilon-proteobacteria) and to some Bacteria belonging to the CFB group. The transfer involved the entire his operon. The hisIE gene fusion was found in several taxonomic lineages and our results suggest that it probably happened several times in distinct lineages. Gene fusions involving hisIE and hisD genes (HIS4) and hisH and hisF genes (HIS7) took place in the Eukarya domain; the latter has been transferred to some delta-proteobacteria. CONCLUSION: Gene duplication is the most widely known mechanism responsible for the origin and evolution of metabolic pathways; however, several other mechanisms might concur in the process of pathway assembly and gene fusion appeared to be one of the most important and common.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Analysis of plasmid genes by phylogenetic profiling and visualization of homology relationships using Blast2Network.

BACKGROUND: Phylogenetic methods are well-established bioinformatic tools for sequence analysis, allowing to describe the non-independencies of sequences because of their common ancestor. However, the evolutionary profiles of bacterial genes are often complicated by hidden paralogy and extensive and/or (multiple) horizontal gene transfer (HGT) events which make bifurcating trees often inappropriate. In this context, plasmid sequences are paradigms of network-like relationships characterizing the evolution of prokaryotes. Actually, they can be transferred among different organisms allowing the dissemination of novel functions, thus playing a pivotal role in prokaryotic evolution. However, the study of their evolutionary dynamics is complicated by the absence of universally shared genes, a prerequisite for phylogenetic analyses. RESULTS: To overcome such limitations we developed a bioinformatic package, named Blast2Network (B2N), allowing the automatic phylogenetic profiling and the visualization of homology relationships in a large number of plasmid sequences. The software was applied to the study of 47 completely sequenced plasmids coming from Escherichia, Salmonella and Shigella spps. CONCLUSION: The tools implemented by B2N allow to describe and visualize in a new way some of the evolutionary features of plasmid molecules of Enterobacteriaceae; in particular it helped to shed some light on the complex history of Escherichia, Salmonella and Shigella plasmids and to focus on possible roles of unannotated proteins.The proposed methodology is general enough to be used for comparative genomic analyses of bacteria.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Biotechnology in the Conservation Field: Removal of Sulphates Using Bacteria and Bioconsolidation of Paintings and Stuccos

The aim of this study was to explore the use of biotechnologies in the restoration of wall paintings and stuccos which often show a great complexity regarding constitutive materials and conservative conditions. ‘Biological methods’ were compared to traditional methods, focusing on restoring the cohesion of the superficial layers (bioconsolidation) and the removal of sulphates (biocleaning) often found on the frescoes as decay products. The experimentation took place as part of a graduate thesis and was divided in two stages: the first was spent in the laboratory working on samples of painted plaster and the second was spent in situ, on the frescoes and stuccos in the Church of Santa Pudenziana in Rome, Italy. Application of the products was followed by a campaign of investigations aimed at determining the efficacy, and the advantages and disadvantages of these methods compared to conventional ones