TFAM detects co-evolution of tRNA identity rules with lateral transfer of histidyl-tRNA synthetase

We present TFAM, an automated, statistical method to classify the identity of tRNAs. TFAM, currently optimized for bacteria, classifies initiator tRNAs and predicts the charging identity of both typical and atypical tRNAs such as suppressors with high confidence. We show statistical evidence for extensive variation in tRNA identity determinants among bacterial genomes due to variation in overall tDNA base content. With TFAM we have detected the first case of eukaryotic-like tRNA identity rules in bacteria. An α-proteobacterial clade encompassing Rhizobiales, Caulobacter crescentus and Silicibacter pomeroyi, unlike a sister clade containing the Rickettsiales, Zymomonas mobilis and Gluconobacter oxydans, uses the eukaryotic identity element A73 instead of the highly conserved prokaryotic element C73. We confirm divergence of bacterial histidylation rules by demonstrating perfect covariation of α-proteobacterial tRNA(His) acceptor stems and residues in the motif IIb tRNA-binding pocket of their histidyl-tRNA synthetases (HisRS). Phylogenomic analysis supports lateral transfer of a eukaryotic-like HisRS into the α-proteobacteria followed by in situ adaptation of the bacterial tDNA(His) and identity rule divergence. Our results demonstrate that TFAM is an effective tool for the bioinformatics, comparative genomics and evolutionary study of tRNA identity

Journal Staff

Discoba (Excavata) is an ancient group of eukaryotes with great morphological and ecological diversity. Unlike the other major divisions of Discoba (Jakobida and Euglenozoa), little is known about the mitochondrial DNAs(mtDNAs) of Heterolobosea. We have assembled a complete mtDNA genome from the aggregating heterolobosean amoeba, Acrasis kona, which consists of a single circular highly AT-rich (83.3%) molecule of 51.5 kb. Unexpectedly, A. kona mtDNA is missing roughly 40% of the protein-coding genes and nearly half of the transfer RNAs found in the only other sequenced heterolobosean mtDNAs, those of Naegleria spp. Instead, over a quarter of A. kona mtDNA consists of novel open reading frames. Eleven of the 16 protein-coding genes missing from A. kona mtDNA were identified in its nuclear DNA and polyA RNA, and phylogenetic analyses indicate that at least 10 of these 11 putative nuclear-encoded mitochondrial (NcMt) proteins arose by direct transfer from the mitochondrion. Acrasis kona mtDNA also employs C-to-U type RNA editing, and 12 homologs of DYW-type pentatricopeptide repeat (PPR) proteins implicated in plant organellar RNA editing are found in A. kona nuclear DNA. A mapping of mitochondrial gene content onto a consensus phylogeny reveals a sporadic pattern of relative stasis and rampant gene loss in Discoba. Rampant loss occurred independently in the unique common lineage leading to Heterolobosea + Tsukubamonadida and later in the unique lineage leading to Acrasis. Meanwhile, mtDNA gene content appears to be remarkably stable in the Acrasis sister lineage leading to Naegleria and in their distant relatives Jakobida

Swedish version of Canadian Physiotherapists Arthritis Care Survey – validity and test-retest reliability for use in primary care

Patients with arthritis are often treated in a primary care setting. To study perceived knowledge and skills in arthritis care the questionnaire "Swedish version of the Canadian Physiotherapists Arthritis Care Survey" has been developed for use in rheumatology specialist care. The aim was to study whether the questionnaire were valid and reliable also for use in primary care. To assess face and content validity a focus group of eight physiotherapists working in primary care served as an expert panel. Test-retest was studied in a group of 30 physiotherapists working in primary health care and calculated with ICC /kappa. After some revision, the focus group gave the questionnaire face and content validity. Based on the focus group discussions questions not supported by the aim were removed (content of rheumatology training, certification and extended scope of practice) and four items added concerning recent education and perceived needs in the field. 95% (122/128) of the questions in the revised questionnaire achieved a "fair to good" or "excellent" test-retest reliability (37% and 58%), while 5% (6/128) were classified as "poor". In summary, the questionnaire showed acceptable validity and reliability for most questions. Some of the questions need revision before the questionnaire is used in primary care.Patienter med artros- och artritsjukdomar är vanligt förekommande i primärvården. För att studera vilken upplevd kunskap och kompetens som finns vid omhändertagandet av denna patientgrupp har frågeformuläret ”Svensk version av Canadian Physiotherapists Arthritis Care Survey” tagits fram för sjukgymnaster verksamma inom reumatologisk specialistsjukvård. Syftet med studien var att undersöka om frågeformuläret hade validitet och reliabilitet för användning inom primärvården. Frågeformuläret validerades för face och content validity med hjälp av en fokusgrupp bestående av åtta sjukgymnaster verksamma i primärvården, en expertpanel. Test-retest reliabilitet undersöktes på en grupp av 30 primärvårdssjukgymnaster och beräknades med ICC/kappa. Resultatet visade att frågeformuläret efter viss revision uppnådde face och content validity. Efter diskussion i fokusgruppen togs irrelevanta delar bort som ej stöddes av frågeställningen (utbildning och utbildningsbehov relaterat till grund- och vidareutbildningar samt certifiering och utvidgade ansvarsområden) och fyra frågor lades till om nyligen genomgångna utbildningar och utbildningsbehov inom området och aktuella för primärvården. 95 % (122/128) av frågorna i det omarbetade frågeformuläret uppnådde tillsammans en ”skälig till god” eller ”utmärkt” test-retest reliabilitet (37 % respektive 58 %) medan 5 % (6/128) klassades som ”mycket svaga”. Sammanfattningsvis uppvisade frågeformuläret acceptabel validitet och reliabilitet för de flesta frågor. Några av frågorna bör dock omarbetas innan frågeformuläret används i primärvården

Visualization of pseudogenes in intracellular bacteria reveals the different tracks to gene destruction

Variably present genes and pseudogenes in Rickettsia species tend to have been acquired more recently and to be more divergent from the genes conserved across all specie

Genome dynamics of Bartonella grahamii in micro-populations of woodland rodents

<p>Abstract</p> <p>Background</p> <p>Rodents represent a high-risk reservoir for the emergence of new human pathogens. The recent completion of the 2.3 Mb genome of <it>Bartonella grahamii</it>, one of the most prevalent blood-borne bacteria in wild rodents, revealed a higher abundance of genes for host-cell interaction systems than in the genomes of closely related human pathogens. The sequence variability within the global <it>B. grahamii </it>population was recently investigated by multi locus sequence typing, but no study on the variability of putative host-cell interaction systems has been performed.</p> <p>Results</p> <p>To study the population dynamics of <it>B. grahamii</it>, we analyzed the genomic diversity on a whole-genome scale of 27 <it>B. grahamii </it>strains isolated from four different species of wild rodents in three geographic locations separated by less than 30 km. Even using highly variable spacer regions, only 3 sequence types were identified. This low sequence diversity contrasted with a high variability in genome content. Microarray comparative genome hybridizations identified genes for outer surface proteins, including a repeated region containing the <it>fha </it>gene for filamentous hemaggluttinin and a plasmid that encodes a type IV secretion system, as the most variable. The estimated generation times in liquid culture medium for a subset of strains ranged from 5 to 22 hours, but did not correlate with sequence type or presence/absence patterns of the <it>fha </it>gene or the plasmid.</p> <p>Conclusion</p> <p>Our study has revealed a geographic microstructure of <it>B. grahamii </it>in wild rodents. Despite near-identity in nucleotide sequence, major differences were observed in gene presence/absence patterns that did not segregate with host species. This suggests that genetically similar strains can infect a range of different hosts.</p

Associations between metabolic disorders and risk of cancer in Danish men and women:a nationwide cohort study

BACKGROUND: The prevalence of metabolic disorders is increasing and has been suggested to increase cancer risk, but the relation between metabolic disorders and risk of cancer is unclear, especially in young adults. We investigated the associations between diabetes, hypertension, and hypercholesterolemia on risk of all-site as well as site-specific cancers. METHODS: We consecutively included men and women from nationwide Danish registries 1996–2011, if age 20–89 and without cancer prior to date of entry. We followed them throughout 2012. Metabolic disorders were defined using discharge diagnosis codes and claimed prescriptions. We used time-dependent sex-stratified Poisson regression models adjusted for age and calendar year to assess associations between metabolic disorders, and risk of all-site and site-specific cancer (no metabolic disorders as reference). RESULTS: Over a mean follow-up of 12.6 (±5.7 standard deviations [SD]) years, 4,826,142 individuals (50.2 % women) with a mean age of 41.4 (±18.9 SD) years had 423,942 incident cancers. Incidence rate ratios (IRRs) of all-site cancer in patients with diabetes or hypertension were highest immediately following diagnosis of metabolic disorder. In women, cancer risk associated with diabetes continued to decline albeit remained significant (IRRs of 1.18–1.22 in years 1–8 following diagnosis). For diabetes in men, and hypertension, IRRs stabilized and remained significantly increased after about one year with IRRs of 1.10-1.13 in men for diabetes, and 1.07–1.14 for hypertension in both sexes. Conversely, no association was observed between hypercholesterolemia (treatment with statins) and cancer risk. The association between hypertension and cancer risk was strongest in young adults aged 20–34 and decreased with advancing age. CONCLUSIONS: Diabetes and hypertension were associated with increased risk of all-site cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2122-7) contains supplementary material, which is available to authorized users

The Journey to smORFland

The genome sequences completed so far contain more than 20 000 genes with unknown function and no similarity to genes in other genomes. The origin and evolution of the orphan genes is an enigma. Here, we discuss the suggestion that some orphan genes may represent pseudogenes or short fragments of genes that were functional in the genome of a common ancestor. These may be the remains of unsuccessful duplication or horizontal gene transfer events, in which the acquired sequences have entered the fragmentation process and thereby lost their similarity to genes in other species. This scenario is supported by a recent case study of orphan genes in several closely related species of Rickettsia, where full-length ancestral genes were reconstructed from sets of short, overlapping orphan genes. One of these was found to display similarity to genes encoding proteins with ankyrin-repeat domains

Single-cell genomics reveal low recombination frequencies in freshwater bacteria of the SAR11 clade

Zaremba-Niedzwiedzka K, Viklund J, Zhao W, et al. Single-cell genomics reveal low recombination frequencies in freshwater bacteria of the SAR11 clade. Genome biology. 2013;14(11): R130.BACKGROUND: The SAR11 group of Alphaproteobacteria is highly abundant in the oceans. It contains a recently diverged freshwater clade, which offers the opportunity to compare adaptations to salt- and freshwaters in a monophyletic bacterial group. However, there are no cultivated members of the freshwater SAR11 group and no genomes have been sequenced yet. RESULTS: We isolated ten single SAR11 cells from three freshwater lakes and sequenced and assembled their genomes. A phylogeny based on 57 proteins indicates that the cells are organized into distinct microclusters. We show that the freshwater genomes have evolved primarily by the accumulation of nucleotide substitutions and that they have among the lowest ratio of recombination to mutation estimated for bacteria. In contrast, members of the marine SAR11 clade have one of the highest ratios. Additional metagenome reads from six lakes confirm low recombination frequencies for the genome overall and reveal lake-specific variations in microcluster abundances. We identify hypervariable regions with gene contents broadly similar to those in the hypervariable regions of the marine isolates, containing genes putatively coding for cell surface molecules. CONCLUSIONS: We conclude that recombination rates differ dramatically in phylogenetic sister groups of the SAR11 clade adapted to freshwater and marine ecosystems. The results suggest that the transition from marine to freshwater systems has purged diversity and resulted in reduced opportunities for recombination with divergent members of the clade. The low recombination frequencies of the LD12 clade resemble the low genetic divergence of host-restricted pathogens that have recently shifted to a new host