1,202 research outputs found
On the origin and evolution of biosynthetic pathways: integrating microarray data with structure and organization of the Common Pathway genes
No full textBackground: 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
Defining Orthologs and Pangenome Size Metrics
No full textSince the advent of ultra-massive sequencing techniques, the consequent drop-off in both price and time required made feasible the sequencing of increasingly more genomes from microbes belonging to the same taxonomic unit. Eventually, this led to the concept of pangenome, that is, the entire set of genes present in a group of representatives of the same genus/species, which, in turn, can be divided into core genome, defined as the set of those genes present in all the genomes under study, and a dispensable genome, the set of genes possessed only by one or a subset of organism.When analyzing a pangenome, an interesting point is to measure its size, thus estimating the gene repertoire of a given taxonomic group. This is usually performed counting the novel genes added to the overall pangenome when new genomes are sequenced and annotated. A pangenome can be also classified as open or close: in an open pangenome its size increases indefinitely when adding new genomes; thus sequencing additional strains will likely yield novel genes. Conversely, in a close pangenome, adding new genomes will not lead to the discovery of new coding capabilities.A central point in pangenomics is the definition of homology relationships between genes belonging to different genomes. This may turn into the search of those genes with similar sequences between different organisms (and including both paralogous and orthologous genes).In this chapter, methods for finding groups of orthologs between genomes and for estimating the pangenome size are discussed. Also, working codes to address these tasks are provided
L’intervento sui fondi interprofessionali per la formazione continua. I nuovi fondi di solidarietà
No full textSOMMARIO: 1. Dai fondi interprofessionali per la formazione ai fondi di solidarietà settoriali: l’applicabilità disomogenea dell’articolo 3, comma 13. – 2. Entità, finalizzazione e natura delle risorse confluenti nei fondi di solidarietà. – 3. Il ruolo dei fondi interprofessionali nel sistema della formazione continua. – 4. Nota bibliografica
The role of gene fusions in the evolution of metabolic pathways: the histidine biosynthesis case
No full textBackground: 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
I fondi immobiliari ad apporto specializzati: problematiche gestionali
No full textLe incertezze dei mercati finanziari, il mutamento della normativa comune e tributaria, insieme a una più compiuta conoscenza del mercato immobiliare, hanno portato a una crescente diffusione del veicolo “fondo” quale strumento di investimento in immobili da parte di risparmiatori e investitori sia privati sia istituzionali. Dopo un inizio senza dubbio difficile, i fondi immobiliari italiani occupano, a giugno 2005, una posizione di rilievo nel panorama del risparmio gestito, rappresentando, tuttavia, ancora solo l’1,5% del patrimonio complessivo degli organismi di investimento collettivo del risparmio.
Le opportunità di ulteriore crescita del comparto, di conseguenza, risultano ancora rilevanti. A giugno 2005, infatti, nel paese europeo in cui il mercato dei fondi immobiliari risulta maggiormente sviluppato, la Germania, i veicoli per il real estate rappresentano una quota pari al 20% dell’asset management complessivo.
Il presente contributo intende approfondire l’analisi del profilo di rischio/rendimento di tale prodotto, confrontandolo con il posizionamento degli altri strumenti del mercato immobiliare gestito.
In particolare, il paragrafo 5.2, dopo una breve analisi dell’evoluzione della normativa in materia di fondi immobiliari, approfondisce gli elementi di opportunità e di minaccia che caratterizzano lo strumento del fondo ad apporto privato, dal punto di vista sia del conferente dei beni che del potenziale acquirente delle quote.
Il paragrafo 5.3, invece, analizza il grado di rischio che caratterizza i fondi ad apporto, approfondendo la modalità con cui tali prodotti coniugano l’elevata specializzazione con l’opportuna diversificazione.
Il paragrafo 5.4, infine, presenta alcune considerazioni conclusive sull’analisi svolta. Emerge che il fondo ad apporto privato registra i tassi di sviluppo più intensi, con riferimento soprattutto agli strumenti riservati a investitori qualificati. Essi sembrano caratterizzarsi per una relativamente elevata specializzazione, a scapito di una forse ottimale diversificazione di portafoglio. Inoltre, si sottolinea la necessità che anche le Autorità di Vigilanza si dotino di efficaci strumenti di verifica del grado di diversificazione degli investimenti immobiliari, tenendo presente che la numerosità e le interrelazioni tra variabili sono molto più elevate rispetto a quelle tradizionalmente conosciute nei mercati mobiliari. In questo senso, sarebbe ottimo un livello di vigilanza sui fondi che possa essere in qualche modo “autogestito” dai singoli operatori, in particolare al fine di proporre nuovi strumenti e tecniche innovative di verifica della diversificazione e del rischio degli investimenti
The mosaicism of plasmids revealed by atypical genes detection and analysis
No full textAbstract Background From an evolutionary viewpoint, prokaryotic genomes are extremely plastic and dynamic, since large amounts of genetic material are continuously added and/or lost through promiscuous gene exchange. In this picture, plasmids play a key role, since they can be transferred between different cells and, through genetic rearrangement(s), undergo gene(s) load, leading, in turn, to the appearance of important metabolic innovations that might be relevant for cell life. Despite their central position in bacterial evolution, a massive analysis of newly acquired functional blocks [likely the result of horizontal gene transfer (HGT) events] residing on plasmids is still missing. Results We have developed a computational, composition-based, pipeline to scan almost 2000 plasmids for genes that differ significantly from their hosting molecule. Plasmids atypical genes (PAGs) were about 6% of the total plasmids ORFs and, on average, each plasmid possessed 4.4 atypical genes. Nevertheless, conjugative plasmids were shown to possess an amount of atypical genes than that found in not mobilizable plasmids, providing strong support for the central role suggested for conjugative plasmids in the context of HGT. Part of the retrieved PAGs are organized into (mainly short) clusters and are involved in important biological processes (detoxification, antibiotic resistance, virulence), revealing the importance of HGT in the spreading of metabolic pathways within the whole microbial community. Lastly, our analysis revealed that PAGs mainly derive from other plasmid (rather than coming from phages and/or chromosomes), suggesting that plasmid-plasmid DNA exchange might be the primary source of metabolic innovations in this class of mobile genetic elements. Conclusions In this work we have performed the first large scale analysis of atypical genes that reside on plasmid molecules to date. Our findings on PAGs function, organization, distribution and spreading reveal the importance of plasmids-mediated HGT within the complex bacterial evolutionary network and in the dissemination of important biological traits.</p
CD : Londra città molteplice. Architettura della rigenerazione
No full textIl CD interattivo contiene una documentazione integrativa su alcune opere selezionate tra quelle trattate nel testo: N.Trasi, D.Fondi, M.Del Vecchio (a cura di) Londra città molteplice
Ed. Kappa, Roma, 200
The primordial metabolism: an ancestral interconnection between leucine, arginine, and lysine biosynthesis
No full textAbstract Background It is generally assumed that primordial cells had small genomes with simple genes coding for enzymes able to react with a wide range of chemically related substrates, interconnecting different metabolic routes. New genes coding for enzymes with a narrowed substrate specificity arose by paralogous duplication(s) of ancestral ones and evolutionary divergence. In this way new metabolic pathways were built up by primordial cells. Useful hints to disclose the origin and evolution of ancestral metabolic routes and their interconnections can be obtained by comparing sequences of enzymes involved in the same or different metabolic routes. From this viewpoint, the lysine, arginine, and leucine biosynthetic routes represent very interesting study-models. Some of the lys, arg and leu genes are paralogs; this led to the suggestion that their ancestor genes might interconnect the three pathways. The aim of this work was to trace the evolutionary pathway leading to the appearance of the extant biosynthetic routes and to try to disclose the interrelationships existing between them and other pathways in the early stages of cellular evolution. Results The comparative analysis of the genes involved in the biosynthesis of lysine, leucine, and arginine, their phylogenetic distribution and analysis revealed that the extant metabolic "grids" and their interrelationships might be the outcome of a cascade of duplication of ancestral genes that, according to the patchwork hypothesis, coded for unspecific enzymes able to react with a wide range of substrates. These genes belonged to a single common pathway in which the three biosynthetic routes were highly interconnected between them and also to methionine, threonine, and cell wall biosynthesis. A possible evolutionary model leading to the extant metabolic scenarios was also depicted. Conclusion The whole body of data obtained in this work suggests that primordial cells synthesized leucine, lysine, and arginine through a single common metabolic pathway, whose genes underwent a set of duplication events, most of which can have predated the appearance of the last common universal ancestor of the three cell domains (Archaea, Bacteria, and Eucaryotes). The model proposes a relative timing for the appearance of the three routes and also suggests a possible evolutionary pathway for the assembly of bacterial cell-wall.</p
A new selective force driving metabolic gene clustering
No full textThe evolution of operons has puzzled evolutionary biologists since their discovery, and many theories exist to explain their emergence, spreading, and evolutionary conservation. In this work, we suggest that DNA replication introduces a selective force for the clustering of functionally related genes on chromosomes, which we interpret as a preliminary and necessary step in operon formation. Our reasoning starts from the observation that DNA replication produces copy number variations of genomic regions, and we propose that such changes perturb metabolism. The formalization of this effect by exploiting concepts from metabolic control analysis suggests that the minimization of such perturbations during evolution could be achieved through the formation of gene clusters and operons. We support our theoretical derivations with simulations based on a realistic metabolic network, and we confirm that present-day genomes have a degree of compaction of functionally related genes, which is significantly correlated to the proposed perturbations introduced by replication. The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their first discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis. IMPORTANCE: The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis
Le performances dei fondi comuni di investimento italiani
No full textLa valutazione della performance dei fondi comuni d'investimento richiama da tempo l'attenzione degli economisti finanziari. Ciò trova giustificazione nella rilevanza che il tema riveste, sia in relazione ad una allocazione ottimale del risparmio, sia per la verifica dell'ipotesi di efficienza dei mercati dei capitali. Oggetto di questo studio è la performance assoluta dei fondi, cioè la validità dei fondi in quanto strumento di investimento alternativo ad altri. L'intento è di stabilire se l'operato dei gestori abbia permesso ai fondi di superare i risultati ottenibili da portafogli confrontabili in termini di rischio, ma non gestiti. I risultati dell'analisi econometrica consentono di affermare che, per il campione e per il periodo analizzato, lo strumento fondo di investimento non ha ottenuto, in media, una performance superiore dal lato della selezione titoli, ed ha invece ottenuto delle performances negative dal lato del market timing
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