Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

Toward 959 nematode genomes

The sequencing of the complete genome of the nematode Caenorhabditis elegans was a landmark achievement and ushered in a new era of whole-organism, systems analyses of the biology of this powerful model organism. The success of the C. elegans genome sequencing project also inspired communities working on other organisms to approach genome sequencing of their species. The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla

Fungal genomes tell a story of ecological adaptations

One genome enables a fungus to have various lifestyles and strategies depending on environmental conditions and in the presence of specific counterparts. The nature of their interactions with other living and abiotic elements is a consequence of their osmotrophism. The ability to degrade complex compounds and especially plant biomass makes them a key component of the global carbon circulation cycle. Since the first fungal genomic sequence was published in 1996 mycology has benefited from the technolgical progress. The available data create an unprecedented opportunity to perform massive comparative studies with complex study design variants targeted at all cellular processes.Grzyby odgrywają zasadniczą rolę w ekosystemach jako patogeny, saprotrofy i symbionty. Ich wszechstronne zdolności metaboliczne czynią z nich kluczowe ogniwo w obiegu węgla w przyrodzie. Dla człowieka stanowią głównie źródło infekcji, ale również zyskują na znaczeniu w biotechnologii (Fisher et al. 2012). Grzyby są obecne w naszym otoczeniu w formie zarodników, pełzaków, grzybni i owocników. Te same gatunki grzybów w zależności od warunków otoczenia mogą prezentować rożne formy morfologiczne i tworzyć różne relacje z otoczeniem, na przykład owadobójcze grzyby są często spotykane jako endosymbionty roślin (Spatafora et al. 2007). Całe to bogactwo znajduje odzwierciedlenie w genomach grzybów. Osmotroficzny tryb życia grzybów narzuca charakter interakcji grzybów z otoczeniem, która odbywa się przy pomocy wydzielanych na zewnątrz enzymów rozkładających pożywienie, białek efektorowych oraz toksyn wpływających na inne organizmy. Grzyby posiadają złożone kompozycje wydzielanych cząsteczek oraz transportery błonowe przystosowane do efektywnego przenoszenia związków chemicznych w obu kierunkach (Richards & Talbot 2013). Zdolność do rozkładania ligniny i celulozy odpowiada w dużej mierze za sukces ewolucyjny grzybów. Adaptacja organizmu do nowego ekosystemu zwykle przebiega poprzez duplikację genów z ich późniejszymi asymetrycznymi zmianami prowadzącymi do szybkiej zmiany specyficzności substratowej jednego z paralogów. Wielokrotne duplikacje jednej grupy genów prowadzą do rozrostu rodziny kodowanych przez nie białek i rozszerzenia zakresu możliwości np. rozkładanych przez nie wariantów substratów. Zwiększenie liczby genów związanych z metabolizowaniem danej grupy substratów jest jednym z podstawowych sposobów adaptacji do danej niszy ekologicznej widzianej z perspektywy genomu. Charakterystyczne więc dla grzybów związanych z roślinami będzie kodowanie licznych enzymów degradujących węglowodany, a dla dermatofitów - proteazy i lipazy. Kolejnym poziomem adaptacji patogenów/symbiontów jest zmiana profilu ekspresji genów i stały „wyścig zbrojeń” z gospodarzami. Ponadto geny te często sąsiadują z transpozonami, w obrębie szybciej ewoluującej części genomu. Geny związane z metabolizowaniem ksenobiotyków częściej ulegają też horyzontalnemu transferowi genów aniżeli geny metabolizmu podstawowego. Inna wyróżniającą grzyby cechą jest posiadanie różnorodnych modeli rozmnażania płciowego nawet pomiędzy spokrewnionymi gatunkami. Model rozmnażania jest jednym z ważniejszych sposobów dostosowania do trybu życia. Rozmnażanie jednopłciowe pojawiało się wielokrotnie w ewolucji grzybów i wydaje się być adaptacją do patogennego trybu życia

Systems analysis of host-parasite interactions.

Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies

Comparative genomics of Burkholderia multivorans, a ubiquitous pathogen with a highly conserved genomic structure

The natural environment serves as a reservoir of opportunistic pathogens. A well-established method for studying the epidemiology of such opportunists is multilocus sequence typing, which in many cases has defined strains predisposed to causing infection. Burkholderia multivorans is an important pathogen in people with cystic fibrosis (CF) and its epidemiology suggests that strains are acquired from non-human sources such as the natural environment. This raises the central question of whether the isolation source (CF or environment) or the multilocus sequence type (ST) of B. multivorans better predicts their genomic content and functionality. We identified four pairs of B. multivorans isolates, representing distinct STs and consisting of one CF and one environmental isolate each. All genomes were sequenced using the PacBio SMRT sequencing technology, which resulted in eight high-quality B. multivorans genome assemblies. The present study demonstrated that the genomic structure of the examined B. multivorans STs is highly conserved and that the B. multivorans genomic lineages are defined by their ST. Orthologous protein families were not uniformly distributed among chromosomes, with core orthologs being enriched on the primary chromosome and ST-specific orthologs being enriched on the second and third chromosome. The ST-specific orthologs were enriched in genes involved in defense mechanisms and secondary metabolism, corroborating the strain-specificity of these virulence characteristics. Finally, the same B. multivorans genomic lineages occur in both CF and environmental samples and on different continents, demonstrating their ubiquity and evolutionary persistence

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought