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The origin of the eukaryotic genetic apparatus is thought to be central to understanding the evolution of the eukaryotic cell. Disagreement about the source of the relevant genes has spawned competing hypotheses for the origins of the eukaryote nuclear lineage. The iconic rooted 3-domains tree of life shows eukaryotes and archaebacteria as separate groups that share a common ancestor to the exclusion of eubacteria. By contrast, the eocyte hypothesis has eukaryotes originating within the archaebacteria and sharing a common ancestor with a particular group called the Crenarchaeota or eocytes. Here, we have investigated the relative support for each hypothesis from analysis of 53 genes spanning the 3 domains, including essential components of the eukaryotic nucleic acid replication, transcription, and translation apparatus. As an important component of our analysis, we investigated the fit between model and data with respect to composition. Compositional heterogeneity is a pervasive problem for reconstruction of ancient relationships, which, if ignored, can produce an incorrect tree with strong support. To mitigate its effects, we used phylogenetic models that allow for changing nucleotide or amino acid compositions over the tree and data. Our analyses favor a topology that supports the eocyte hypothesis rather than archaebacterial monophyly and the 3-domains tree of life.

W e need measures and tests of the effects of national values if we are not to over- or under-attribute management behaviour differences to them, but complex institutional and industrial influences make this difficult. Here, we examine international differences in the purposes of firms as expressed by CEOs, which subject to institutional and industrial factors as well as national values. Having explored these purposes in investment decisions of large public companies, we adopted a ‘quasi-experimental’ approach to measure and test national values’ influence in owner-managed firms in different cultures. We found national values influencing business aims, but not time frames or stakeholders, where other forces were acting. So they are important, but we can only reliably attribute behaviour to them on the rare occasions where other forces are not at play. Good measures of values’ effects may themselves aid understanding of the background to international business negotiations and partnerships.

Yersinia enterocolitica is a common cause of food-borne gastroenteritis worldwide. Recent work defining the phylogeny of the genus Yersinia subdivided Y. enterocolitica into six distinct phylogroups. Here, we provide detailed analyses of the evolutionary processes leading to the emergence of these phylogroups. The dominant phylogroups isolated from human infections, PG3-5, show very little diversity at the sequence level, but do present marked patterns of gain and loss of functions, including those involved in pathogenicity and metabolism, including the acquisition of phylogroup-specific O-antigen loci. We tracked gene flow across the species in the core and accessory genome, and show that the non-pathogenic PG1 strains act as a reservoir for diversity, frequently acting as donors in recombination events. Analysis of the core and accessory genome also suggested that the different Y. enterocolitica phylogroups may be ecologically separated, in contrast to the long-held belief of common shared ecological niches across the Y. enterocolitica species.

International audience; Serotype 1 Streptococcus pneumoniae is a leading cause of invasive pneumococcal disease (IPD) worldwide, with the highest burden in developing countries. We report the whole-genome sequencing analysis of 448 serotype 1 isolates from 27 countries worldwide (including 11 in Africa). The global serotype 1 population shows a strong phylogeographic structure at the continental level, and within Africa there is further region-specific structure. Our results demonstrate that region-specific diversification within Africa has been driven by limited cross-region transfer events, genetic recombination and antimicrobial selective pressure. Clonal replacement of the dominant serotype 1 clones circulating within regions is uncommon; however, here we report on the accessory gene content that has contributed to a rare clonal replacement event of ST3081 with ST618 as the dominant cause of IPD in the Gambia.

Streptococcus pneumoniae is a nasopharyngeal commensal that occasionally invades normally sterile sites to cause bloodstream infection and meningitis. Although the pneumococcal population structure and evolutionary genetics are well defined, it is not clear whether pneumococci that cause meningitis are genetically distinct from those that do not. Here, we used whole-genome sequencing of 140 isolates of S. pneumoniae recovered from bloodstream infection ( n = 70) and meningitis ( n = 70) to compare their genetic contents. By fitting a double-exponential decaying-function model, we show that these isolates share a core of 1,427 genes (95% confidence interval [CI], 1,425 to 1,435 genes) and that there is no difference in the core genome or accessory gene content from these disease manifestations. Gene presence/absence alone therefore does not explain the virulence behavior of pneumococci that reach the meninges. Our analysis, however, supports the requirement of a range of previously described virulence factors and vaccine candidates for both meningitis- and bacteremia-causing pneumococci. This high-resolution view suggests that, despite considerable competency for genetic exchange, all pneumococci are under considerable pressure to retain key components advantageous for colonization and transmission and that these components are essential for access to and survival in sterile sites.

© 2015 Elsevier Ltd. Background: Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK. Methods: We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships. Findings: We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection). Interpretation: We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM. Funding: Wellcome Trust (grant number 098051).

The assembly of DNA sequence data is undergoing a renaissance thanks to emerging technologies capable of producing reads tens of kilobases long. Assembling complete bacterial and small eukaryotic genomes is now possible, but the final step of circularizing sequences remains unsolved. Here we present Circlator, the first tool to automate assembly circularization and produce accurate linear representations of circular sequences. Using Pacific Biosciences and Oxford Nanopore data, Circlator correctly circularized 26 of 27 circularizable sequences, comprising 11 chromosomes and 12 plasmids from bacteria, the apicoplast and mitochondrion of Plasmodium falciparum and a human mitochondrion. Circlator is available at http://sanger-pathogens.github.io/circlator/. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0849-0) contains supplementary material, which is available to authorized users.

Bordetella pertussis is the causative agent of whooping cough, a highly contagious, acute respiratory illness that has seen resurgence despite the use of vaccines. We present the complete genome sequence of a clinical strain of B. pertussis , D420, which is representative of a currently circulating clade of this pathogen.

International audience; The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.

Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population., Author Summary Salmonella enterica is a diverse species, isolates of which can colonise or infect many different animals, including humans and can cause different disease syndromes. S. enterica can be sub-typed using serology into serovars. Isolates from some serovars, known as generalists, can infect multiple hosts (e.g. S. Typhimurium) and usually cause gastroenteritis. However, other serovars exhibit host adaptation or even restriction. Host-adapted serovars such as S. Dublin show preference for a particular host but can also infect other hosts, while host-restricted serovars are capable of infecting only a single host (e.g. S. Typhi in humans) and frequently cause febrile systemic disease (typhoid). In this study, we use genotypic and phenotypic methods to investigate clinical isolates representative of populations of two recently emerged S. Typhimurium lineages of type ST313 associated with invasive disease in sub-Saharan Africa. Our results identify potential characteristics in these isolates that may be associated with adaptation to invasive disease in humans with a compromised immunity.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally and is increasingly prevalent in India. Here, we present the complete genome sequence of DAR4145, a strain of the ST772-MRSA-V lineage from India, and investigate its genomic characteristics in regards to antibiotic resistance and virulence factors. Results Sequencing using single-molecule real-time technology resulted in the assembly of a single continuous chromosomal sequence, which was error-corrected, annotated and compared to nine draft genome assemblies of ST772-MRSA-V from Australia, Malaysia and India. We discovered numerous and redundant resistance genes associated with mobile genetic elements (MGEs) and known core genome mutations that explain the highly antibiotic resistant phenotype of DAR4145. Staphylococcal toxins and superantigens, including the leukotoxin Panton-Valentinin Leukocidin, were predominantly associated with genomic islands and the phage φ-IND772PVL. Some of these mobile resistance and virulence factors were variably present in other strains of the ST772-MRSA-V lineage. Conclusions The genomic characteristics presented here emphasize the contribution of MGEs to the emergence of multidrug-resistant and highly virulent strains of community-associated MRSA. Antibiotic resistance was further augmented by chromosomal mutations and redundancy of resistance genes. The complete genome of DAR4145 provides a valuable resource for future investigations into the global dissemination and phylogeography of ST772-MRSA-V. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1599-9) contains supplementary material, which is available to authorized users.

Serotype 1 Streptococcus pneumoniae is a leading cause of invasive pneumococcal disease (IPD) worldwide, with the highest burden in developing countries. We report the whole-genome sequencing analysis of 448 serotype 1 isolates from 27 countries worldwide (including 11 in Africa). The global serotype 1 population shows a strong phylogeographic structure at the continental level, and within Africa there is further region-specific structure. Our results demonstrate that region-specific diversification within Africa has been driven by limited cross-region transfer events, genetic recombination and antimicrobial selective pressure. Clonal replacement of the dominant serotype 1 clones circulating within regions is uncommon; however, here we report on the accessory gene content that has contributed to a rare clonal replacement event of ST3081 with ST618 as the dominant cause of IPD in the Gambia.

SRH, SDB JP and MTGH were supported by Wellcome Trust grant 098051. LYH was funded by the National Medical Research Council Singapore. SP is funded by the UKCRC Translational Infection Research Initiative, and the NIHR Cambridge Biomedical Research Centre. Background In the past decade, several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment. One example is Singapore, where MRSA ST239, the dominant clone since molecular profiling of MRSA began in the mid-1980s, has been replaced by ST22 isolates belonging to EMRSA-15, a recently emerged pandemic lineage originating from Europe. Results We investigated the population structure of MRSA in Singaporean hospitals spanning three decades, using whole genome sequencing. Applying Bayesian phylogenetic methods we report that prior to the introduction of ST22, the ST239 MRSA population in Singapore originated from multiple introductions from the surrounding region; it was frequently transferred within the healthcare system resulting in a heterogeneous hospital population. Following the introduction of ST22 around the beginning of the millennium, this clone spread rapidly through Singaporean hospitals, supplanting the endemic ST239 population. Coalescent analysis revealed that although the genetic diversity of ST239 initially decreased as ST22 became more dominant, from 2007 onwards the genetic diversity of ST239 began to increase once more, which was not associated with the emergence of a sub-clone of ST239. Comparative genomic analysis of the accessory genome of the extant ST239 population identified that the Arginine Catabolic Mobile Element arose multiple times, thereby introducing genes associated with enhanced skin colonization into this population. Conclusions Our results clearly demonstrate that, alongside clinical practice and antibiotic usage, competition between clones also has an important role in driving the evolution of nosocomial pathogen populations. Publisher PDF

Objectives Genome sequencing will be increasingly used in the clinical setting to tailor antimicrobial prescribing and inform infection control outbreaks. A recent technological innovation that could reduce the delay between pathogen sampling and data generation is single molecule sequencing. An example of this technology, which is undergoing evaluation through an early access programme, is the Oxford Nanopore MinION. Methods We undertook a feasibility study on six clinically significant pathogens, comparing the MinION to the Illumina MiSeq and PacBio RSII platforms. Genomic DNA was prepared and sequenced using the MinION as instructed by the manufacturer, and Illumina MiSeq and PacBio sequencing was performed using established methods. Results An evaluation of the accuracy of the MinION based on sequencing of an MRSA isolate showed that error rates were higher in the MinION reads, but provided an even coverage across the entire genome length. The MinION detected all of the expected carbapenemases and ESBL genes in five Gram-negative isolates and the mecA gene in an MRSA isolate. Conclusions The MinION can detect the presence of acquired resistance genes, but improvements in accuracy are needed so that antimicrobial resistance associated with mutations in chromosomal genes can be identified.

The emergence of new sequencing technologies has facilitated the use of bacterial whole genome alignments for evolutionary studies and outbreak analyses. These datasets, of increasing size, often include examples of multiple different mechanisms of horizontal sequence transfer resulting in substantial alterations to prokaryotic chromosomes. The impact of these processes demands rapid and flexible approaches able to account for recombination when reconstructing isolates’ recent diversification. Gubbins is an iterative algorithm that uses spatial scanning statistics to identify loci containing elevated densities of base substitutions suggestive of horizontal sequence transfer while concurrently constructing a maximum likelihood phylogeny based on the putative point mutations outside these regions of high sequence diversity. Simulations demonstrate the algorithm generates highly accurate reconstructions under realistically parameterized models of bacterial evolution, and achieves convergence in only a few hours on alignments of hundreds of bacterial genome sequences. Gubbins is appropriate for reconstructing the recent evolutionary history of a variety of haploid genotype alignments, as it makes no assumptions about the underlying mechanism of recombination. The software is freely available for download at github.com/sanger-pathogens/Gubbins, implemented in Python and C and supported on Linux and Mac OS X.

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource-poor hospital settings. Through whole-genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high-dependency wards in a hospital in Kathmandu during 2012 with a case-fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage-specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward-specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM-1 containing lineage in 2011 would have alerted the high-dependency ward staff to intervene. We argue that some form of real-time genetic characterisation, alongside clade-specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high- and low-income settings.

Take the linearised FKPP equation \[\partial_t h =\partial^2_x h +h\] with boundary condition $h(m(t),t)=0$. Depending on the behaviour of the initial condition $h_0(x)=h(x,0)$ we obtain the asymptotics - up to a $o(1)$ term $r(t)$ - of the absorbing boundary $m(t)$ such that $\omega(x):=\lim_t h(x+m(t) ,t)$ exists and is non-trivial. In particular, as in Bramson's results for the non-linear FKPP equation, we recover the celebrated $-(3/2)\log t$ correction for initial conditions decaying faster than $x^\nu e^{-x}$ for some $\nu, Comment: 30 pages

We give a new, intuitive and relatively straightforward proof of a path large-deviations result for branching Brownian motion (BBM) that can be thought of as extending Schilder’s theorem for a single Brownian motion. Our conceptual approach provides an elegant and striking new application of a change of measure technique that induces a ‘spine’ decomposition and builds on the new foundations for the use of spines in branching diffusions recently developed in Hardy and Harris [Robert Hardy, Simon C. Harris, A new formulation of the spine approach to branching diffusions, 2004, no. 0404, Mathematics Preprint, University of Bath. http://www.bath.ac.uk/~massch/Research/Papers/spine-foundations.pdf ; Robert Hardy, Simon C. Harris, Spine proofs for L p -convergence of branching-diffusion martingales, 2004, no. 0405, Mathematics Preprint, University of Bath. http://www.bath.ac.uk/~massch/Research/Papers/spine-Lp-cgce.pdf ], itself inspired by related works of Kyprianou [Andreas Kyprianou, Travelling wave solutions to the K–P–P equation: alternatives to Simon Harris’s probabilistic analysis, Ann. Inst. H. Poincare Probab. Statist. 40 (1) (2004) 53–72] and Lyons et al. [Russell Lyons, A simple path to Biggins’ martingale convergence for branching random walk, in: Classical and Modern Branching Processes (Minneapolis, MN, 1994), IMA Vol. Math. Appl., vol. 84, Springer, New York, 1997, pp. 217–221; Thomas Kurtz, Russell Lyons, Robin Pemantle, Yuval Peres, A conceptual proof of the Kesten–Stigum theorem for multi-type branching processes, in: Classical and Modern Branching Processes (Minneapolis, MN, 1994), IMA Vol. Math. Appl., vol. 84, Springer, New York, 1997, pp. 181–185; Russell Lyons, Robin Pemantle, Yuval Peres, Conceptual proofs of L log L criteria for mean behavior of branching processes, Ann. Probab. 23 (3) (1995) 1125–1138]. Some of the techniques developed here will also apply in more general branching Markov processes, for example, see Hardy and Harris [Robert Hardy, Simon C. Harris, A spine proof of a lower bound for a typed branching diffusion, 2004, no. 0408, Mathematics Preprint, University of Bath. http://www.bath.ac.uk/~massch/Research/Papers/spine-oubbm.pdf ].

At the heart of this article will be the study of a branching Brownian motion (BBM) with killing, where individual particles move as Brownian motions with drift −ρ, perform dyadic branching at rate β and are killed on hitting the origin. Firstly, by considering properties of the right-most particle and the extinction probability, we will provide a probabilistic proof of the classical result that the ‘one-sided’ FKPP travelling-wave equation of speed −ρ with solutions f : [ 0 , ∞ ) → [ 0 , 1 ] satisfying f ( 0 ) = 1 and f ( ∞ ) = 0 has a unique solution with a particular asymptotic when ρ 2 β , and no solutions otherwise. Our analysis is in the spirit of the standard BBM studies of [S.C. Harris, Travelling-waves for the FKPP equation via probabilistic arguments, Proc. Roy. Soc. Edinburgh Sect. A 129 (3) (1999) 503–517] and [A.E. Kyprianou, Travelling wave solutions to the K-P-P equation: alternatives to Simon Harris' probabilistic analysis, Ann. Inst. H. Poincare Probab. Statist. 40 (1) (2004) 53–72] and includes an intuitive application of a change of measure inducing a spine decomposition that, as a by product, gives the new result that the asymptotic speed of the right-most particle in the killed BBM is 2 β − ρ on the survival set. Secondly, we introduce and discuss the convergence of an additive martingale for the killed BBM, W λ , that appears of fundamental importance as well as facilitating some new results on the almost-sure exponential growth rate of the number of particles of speed λ ∈ ( 0 , 2 β − ρ ) . Finally, we prove a new result for the asymptotic behaviour of the probability of finding the right-most particle with speed λ > 2 β − ρ . This result combined with Chauvin and Rouault's [B. Chauvin, A. Rouault, KPP equation and supercritical branching Brownian motion in the subcritical speed area. Application to spatial trees, Probab. Theory Related Fields 80 (2) (1988) 299–314] arguments for standard BBM readily yields an analogous Yaglom-type conditional limit theorem for the killed BBM and reveals W λ as the limiting Radon–Nikodým derivative when conditioning the right-most particle to travel at speed λ into the distant future.

Using a simple example and simulations, we explore the impact of input tree shape upon a broad range of supertree methods. We find that input tree shape can affect how conflict is resolved by several supertree methods and that input tree shape effects may be substantial. Standard and irreversible matrix representation with parsimony (MRP), MinFlip, duplication-only Gene Tree Parsimony (GTP), and an implementation of the average consensus method have a tendency to resolve conflict in favor of relationships in unbalanced trees. Purvis MRP and the average dendrogram method appear to have an opposite tendency. Biases with respect to tree shape are correlated with objective functions that are based upon unusual asymmetric tree-to-tree distance or fit measures. Split, quartet, and triplet fit, most similar supertree, and MinCut methods (provided the latter are interpreted as Adams consensus-like supertrees) are not revealed to have any bias with respect to tree shape by our example, but whether this holds more generally is an open problem. Future development and evaluation of supertree methods should consider explicitly the undesirable biases and other properties that we highlight. In the meantime, use of a single, arbitrarily chosen supertree method is discouraged. Use of multiple methods and/or weighting schemes may allow practical assessment of the extent to which inferences from real data depend upon methodological biases with respect to input tree shape or size.

The importance of inter-personal relationships has increasingly been acknowledged in entrepreneurship and international business research. This paper focuses on the role of entrepreneurs' inter-personal relationships in the internationalization process, addressing three broad questions: what are the functions of relationships in the internationalization process; from where do the important relationships originate; and what strategies of relationship development do entrepreneurs pursue? These issues are explored in the important relationships of three successful international entrepreneurs that are examined in depth. The cases indicate that the functions of inter-personal relationships in the internationalization process are much more profound than previous research would indicate. They can direct strategy and transform the firm, not just provide information and access to networks. The origins of the relationships are wide, spanning ‘social/personal’ and ‘business’ situations. For entrepreneurs, the ‘planned’ approach of relationships and network development in foreign markets advocated in much of the normative marketing literature may not be relevant. Instead, entrepreneurs might look to strong, deep, inter-personal relationships from which to build transformational international development of their firms.

This study examines the effect of diverse national values on strategic investment decision (SID) making in the context of industry globalization. Whilst previous single country studies of strategic decision making have highlighted the effect of variables such as uncertainty, environmental stability, competition intensity and organizational position, we argue that diverse national values are also critical, albeit tempered by convergence pressures arising from globalization. Our incipient model, recognizing research from both these fields, is explored in closely matched automotive components businesses, one German, one American, one British and one Japanese. Transcripts of interviews focusing on recent SIDs were analysed against protocols generated from the alternative propositions. We found considerable diversity associated with differences in national values in respect to techniques, but also some points of convergence in respect to other process aspects driven by common industrial globalization pressures.

Character construction, the methods by which characters and character states are produced from observations of variation, is a crucial but poorly understood step in phylogenetic analysis. Alternative approaches are used in practice, but there has been relatively little investigation of their theoretical bases and analytical consequences. We reviewed three published numerical analyses of the phylogenetic relationships within the Triassic Aetosauria. Combined data from these studies were used to explore the impact of alternative approaches to character construction. Some previous aetosaurian characters represent parallel variations in the morphology of osteoderms from different body regions, and their independence is questionable, leading us to propose more composite alternative constructions. Phylogenetic analyses revealed that inferred relationships within the Aetosauria are in general poorly resolved and weakly supported by the available data and are sensitive to alternative approaches to character construction. Thus, the results from this and previous studies should not, for the most part, be accepted as robust hypotheses of aetosaurian interrelationships. The treatment of systems of intraorganismal (e.g. serial, antimeric) homologues, such as osteoderms, in character construction is discussed. Applied to parallel variations in systems of intraorganismal homologues, previous advice on choosing among alternative character constructions and Hennig's auxiliary principle agree in favoring a more composite approach, in accordance with common practice.

The results of high-resolution whole-genome sequencing data provide compelling evidence that Mycoplasma amphoriforme produces chronic relapsing infection and, importantly, is transmitted in a hospital environment., Background. Mycoplasma amphoriforme has been associated with infection in patients with primary antibody deficiency (PAD). Little is known about the natural history of infection with this organism and its ability to be transmitted in the community. Methods. The bacterial load was estimated in sequential sputum samples from 9 patients by quantitative polymerase chain reaction. The genomes of all available isolates, originating from patients in the United Kingdom, France, and Tunisia, were sequenced along with the type strain. Genomic data were assembled and annotated, and a high-resolution phylogenetic tree was constructed. Results. By using high-resolution whole-genome sequencing (WGS) data, we show that patients can be chronically infected with M. amphoriforme manifesting as a relapsing-remitting bacterial load, interspersed by periods when the organism is undetectable. Importantly, we demonstrate transmission of strains within a clinical environment. Antibiotic resistance mutations accumulate in isolates taken from patients who received multiple courses of antibiotics. Conclusions. Mycoplasma amphoriforme isolates form a closely related species responsible for a chronic relapsing and remitting infection in PAD patients in the United Kingdom and from immunocompetent patients in other countries. We provide strong evidence of transmission between patients attending the same clinic, suggesting that screening and isolation may be necessary for susceptible patients. This work demonstrates the critical role that WGS can play in rapidly unraveling the biology of a novel pathogen.

BACKGROUND: \ud \ud Wolbachia intracellular bacteria can manipulate the reproduction of their arthropod hosts, including inducing sterility between populations known as cytoplasmic incompatibility (CI). Certain strains have been identified that are unable to induce or rescue CI, including wAu from Drosophila. Genome sequencing and comparison with CI-inducing related strain wMel was undertaken in order to better understand the molecular basis of the phenotype.\ud \ud RESULTS: \ud \ud Although the genomes were broadly similar, several rearrangements were identified, particularly in the prophage regions. Many orthologous genes contained single nucleotide polymorphisms (SNPs) between the two strains, but a subset containing major differences that would likely cause inactivation in wAu were identified, including the absence of the wMel ortholog of a gene recently identified as a CI candidate in a proteomic study. The comparative analyses also focused on a family of transcriptional regulator genes implicated in CI in previous work, and revealed numerous differences between the strains, including those that would have major effects on predicted function.\ud \ud CONCLUSIONS: \ud \ud The study provides support for existing candidates and novel genes that may be involved in CI, and provides a basis for further functional studies to examine the molecular basis of the phenotype.

Recent data revolution in population genomics for bacteria has increased the size of aligned sequence data sets by two-to-three orders of magnitude. This trend is expected to continue in the near future, putting an emphasis on applicability of big data techniques to leverage biologically important insights. Moreover, with the increasing density of sampling, it may also be necessary to consider alignment-free sequence analysis techniques combined with clustering to yield a sufficient insight to data. This leads to ultra high-dimensional data with tens of millions of variables, which can no longer be handled by the existing population genomic methods. Using the largest bacterial sequence data sets published to date, we demonstrate that random projection based clustering provides a highly accurate and several orders of magnitude faster approach to the analysis of both alignment-based and alignment-free genome data sets, compared with the Bayesian model-based analysis that is currently considered as the state-of-the-art. Hence, clustering methods for big data harbor considerable potential for important applications in genomics and could pave way for novel analysis pipelines even in the online setting when executed in a massively parallel computing environment.

Traditional genetic association studies are very difficult in bacteria, as the generally limited recombination leads to large linked haplotype blocks, confounding the identification of causative variants. Beta-lactam antibiotic resistance in Streptococcus pneumoniae arises readily as the bacteria can quickly incorporate DNA fragments encompassing variants that make the transformed strains resistant. However, the causative mutations themselves are embedded within larger recombined blocks, and previous studies have only analysed a limited number of isolates, leading to the description of “mosaic genes” as being responsible for resistance. By comparing a large number of genomes of beta-lactam susceptible and non-susceptible strains, the high frequency of recombination should break up these haplotype blocks and allow the use of genetic association approaches to identify individual causative variants. Here, we performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) and indels that could confer beta-lactam non-susceptibility using 3,085 Thai and 616 USA pneumococcal isolates as independent datasets for the variant discovery. The large sample sizes allowed us to narrow the source of beta-lactam non-susceptibility from long recombinant fragments down to much smaller loci comprised of discrete or linked SNPs. While some loci appear to be universal resistance determinants, contributing equally to non-susceptibility for at least two classes of beta-lactam antibiotics, some play a larger role in resistance to particular antibiotics. All of the identified loci have a highly non-uniform distribution in the populations. They are enriched not only in vaccine-targeted, but also non-vaccine-targeted lineages, which may raise clinical concerns. Identification of single nucleotide polymorphisms underlying resistance will be essential for future use of genome sequencing to predict antibiotic sensitivity in clinical microbiology., Author Summary Streptococcus pneumoniae is carried asymptomatically in the nasopharyngeal tract. However, it is capable of causing multiple diseases, including pneumonia, bacteraemia and meningitis, which are common causes of morbidity and mortality in young children. Antibiotic treatment has become more difficult, especially that involving the group of beta-lactam antibiotics where resistance has developed rapidly. The organism is known to be highly recombinogenic, and this allows variants conferring beta-lactam resistance to be readily introduced into the genome. Identification of the specific genetic determinants of beta-lactam resistance is essential to understand both the mechanism of resistance and the spread of resistant variants in the pneumococcal population. Here, we performed a genome-wide association study on 3,701 isolates collected from two different locations and identified candidate variants that may explain beta-lactam resistance as well as discriminating potential genetic hitchhiking variants from potential causative variants. We report 51 loci, containing 301 SNPs, that are associated with beta-lactam non-susceptibility. 71 out of 301 polymorphic changes result in amino acid alterations, 28 of which have been reported previously. Understanding the determinants of resistance at the single nucleotide level will be important for the future use of sequence data to predict resistance in the clinical setting.

cturers that are expanding into emerging markets to access both markets and production resources there. By examining one specific western manufacturer that is making this journey in some detail, it develops a systems framework that helps the overall system complexity to be deconstructed, and to be presented as an overall global factory ‘system of systems’, that links three specific systems: a production system, an innovation system, and a management system. We argue that this PIM (Production – Innovation – Management) segmentation of the system complexity, combined with the business process system that links them together within the global factory environment, represents a useful contribution for helping firms to address the complexities that they face when expanding from being nationally based international manufacturers, to being Global Factories.

Background: Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain 6B -2) clone of Streptococcus pneumoniae. Results: Whole genome sequencing of an international collection of 189 isolates estimated that PMEN2 emerged around the late 1960s, developing resistance through multiple homologous recombinations and the acquisition of a Tn5253-type integrative and conjugative element (ICE). Two distinct clades entered Iceland in the 1980s, one of which had acquired a macrolide resistance cassette and was estimated to have risen sharply in its prevalence by coalescent analysis. Transmission within the island appeared to mainly emanate from Reykjavik and the Southern Peninsular, with evolution of the bacteria effectively clonal, mainly due to a prophage disrupting a gene necessary for genetic transformation in many isolates. A subsequent decline in PMEN2’s prevalence in Iceland coincided with a nationwide campaign that reduced dispensing of antibiotics to children in an attempt to limit its spread. Specific mutations causing inactivation or loss of ICE-borne resistance genes were identified from the genome sequences of isolates that reverted to drug susceptible phenotypes around this time. Phylogenetic analysis revealed some of these occurred on multiple occasions in parallel, suggesting they may have been at least temporarily advantageous. However, alteration of ‘core’ sequences associated with resistance was precluded by the absence of any substantial homologous recombination events. Conclusions: PMEN2’s clonal evolution was successful over the short-term in a limited geographical region, but its inability to alter major antigens or ‘core’ gene sequences associated with resistance may have prevented persistence over longer timespans.

IJV research highlights the importance of learning in international joint ventures (IJVs) but has not indicated how to achieve it. We combine organizational learning and internationalization process research within a microfoundations framework to understand learning in IJVs. We study a Samsung-Tesco IJV that successfully learned retail practice from one partner and applied it in a South Korean context known by the other. The managers used many learning processes, not just experiential learning emphasized in international business research, and used many more knowledge sources than assumed in prior research, including the IJV partners’ other subsidiaries. To build absorptive capacity, IJVs need appropriate microfoundations at individual, process and structural levels, and coherent interlinkages between them, especially by having IJV managers’ with extensive experience and orientation to learn who are given structural and process autonomy to invest in learning.

Background The term ‘zero tolerance’ has recently been applied to healthcare-associated infections, implying that such events are always preventable. This may not be the case for healthcare-associated infections such as methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Methods We combined information from an epidemiological investigation and bacterial whole-genome sequencing to evaluate a cluster of five MRSA bacteraemia episodes in four patients in a specialist hepatology unit. Results The five MRSA bacteraemia isolates were highly related by multilocus sequence type (ST) (four isolates were ST22 and one isolate was a single-locus variant, ST2046). Whole-genome sequencing demonstrated unequivocally that the bacteraemia cases were unrelated. Placing the MRSA bacteraemia isolates within a local and global phylogenetic tree of MRSA ST22 genomes demonstrated that the five bacteraemia isolates were highly diverse. This was consistent with the acquisition and importation of MRSA from the wider referral network. Analysis of MRSA carriage and disease in patients within the hepatology service demonstrated a higher risk of both initial MRSA acquisition compared with the nephrology service and a higher risk of progression from MRSA carriage to bacteraemia, compared with patients in nephrology or geriatric services. A root cause analysis failed to reveal any mechanism by which three of five MRSA bacteraemia episodes could have been prevented. Conclusions This study illustrates the complex nature of MRSA carriage and bacteraemia in patients in a specialized hepatology unit. Despite numerous ongoing interventions to prevent MRSA bacteraemia in healthcare settings, these are unlikely to result in a zero incidence in referral centres that treat highly complex patients.

Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines., La lista completa de autores que integran el documento puede consultarse en el archivo., Instituto de Biotecnologia y Biologia Molecular

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those fromEurope, supporting the assumption that human tuberculosis was introduced post-contact1. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World2. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch3, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-oldmycobacterial genomesfromPeruvianhuman skeletons, revealing that amember of the M. tuberculosis complex caused human disease before contact.The ancient strains are distinct fromknownhuman-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean. Fil: Bos, Kirsten I.. Universitat Tubingen; Alemania Fil: Harkins, Kelly M.. Arizona State University; Estados Unidos Fil: Herbig, Alexander. Universitat Tubingen; Alemania Fil: Coscolla, Mireia. University of Basel; Suiza. Swiss Tropical and Public Health Institute; Suiza Fil: Weber, Nico. University of Tübingen; Alemania Fil: Comas, Iñaki. FISABIO-Public Health; España. Universidad Carlos III de Madrid. Instituto de Salud; España Fil: Forrest, Stephen A.. University of Tübingen; Alemania Fil: Bryant, Josephine M.. Wellcome Trust Sanger Institute; Reino Unido Fil: Harris, Simon R.. Wellcome Trust Sanger Institute; Reino Unido Fil: Schuenemann, Verena J.. University of Tübingen; Alemania Fil: Campbell, Tessa J.. University Of Cape Town; Estados Unidos Fil: Majander, Kerttu. University of Tübingen; Alemania Fil: Wilbur, Alicia K.. Arizona State University; Estados Unidos Fil: Guichon, Ricardo Anibal. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina Fil: Steadman, Dawnie L. Wolfe. University of Tennessee; Estados Unidos Fil: Cook, Della Collins. Indiana University; Estados Unidos Fil: Niemann, Stefan. Forschungszentrum Borstel - Zentrum Fur Medizin Und Biowissenschaften; Alemania Fil: Behr, Marcel A.. Mcgill University; Canadá Fil: Zumárraga, Martín José. Biotechnology Institute; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina Fil: Bastida, Ricardo. Universidad Nacional de Mar del Plata; Argentina Fil: Huson, Daniel. University of Tübingen; Alemania Fil: Nieselt, Kay. University of Tübingen; Alemania Fil: Young, Douglas. Imperial College London; Reino Unido. National Institute for Medical Research; Reino Unido Fil: Parkhill, Julian. Wellcome Trust Sanger Institute; Reino Unido Fil: Buikstra, Jane E.. Arizona State University; Estados Unidos Fil: Gagneux, Sebastien. Universitat Basel; Suiza. Swiss Tropical and Public Health Institute; Suiza Fil: Stone, Anne C.. Arizona State University; Estados Unidos Fil: Krause, Johannes. Max Planck Institute for Science and History; Alemania. University of Tübingen; Alemania

Recurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection.We assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence.We assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease.Whole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials.Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.

International audience; This volume provides a broad insight on current, high level researches in probability theory.

Two American football players on the same team were diagnosed with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections on the same day. Our investigation, including whole genome sequencing, confirmed that players did not transmit MRSA to one another nor did they acquire the MRSA from a single source within the training facility.

We demonstrate a novel strong law of large numbers for branching processes, with a simple proof via measure-theoretic manipulations and spine theory. Roughly speaking, any sequence of events that eventually occurs almost surely for the spine entails the almost sure convergence of a certain sum over particles in the population., Comment: 6 pages

The advent of DNA sequencing technologies with the capability to sequence the entire genomes of large numbers of bacteria in clinically relevant timescales has opened up the opportunity of using whole-genome sequencing as an epidemiological tool. With costs of sequencing also reducing, we are on the verge of a genomic epidemiology revolution that will provide a method that is both more widely applicable and more detailed than any other current bacterial typing technique. However, the wealth of information provided by whole-genome sequencing requires novel analysis techniques and a review of the current ways of interpreting epidemiological relatedness. This will entail a shift from a same-versus-different methodology to a hierarchical approach that provides a more realistic representation of bacterial evolution. In this chapter, we describe some of the methods by which sequence data can be analysed to identify genomic variation and how genomic relatedness of bacteria can be used alongside traditional epidemiological evidence to draw conclusions about the nature of bacterial disease outbreaks and transmission chains.

The use of ‘native categories’ in management research avoids the input of researchers' a priori understandings into the research process. The rich, unobservable and subjective perceptions of managers may be explored through interpretative research approaches, but these do not meet the positive aspiration of generating findings of generalisable application. A gulf exists between these two research approaches. An approach is described and evaluated which, in attempting to address the ‘native category’ problem in a comparative management research study, reconciles many of the objectives of interpretative and positive research. It explicitly recognises imperfection in all research approaches, and strikes a range of appropriate compromises. It is a way of accessing managers' ‘native category’ data results that is amenable to interpretative and positive, qualitative and quantitative analysis. The approach presented shows that the gulf between interpretative and positive approaches may be bridged, and other ‘bridges’ may be developed for other research enquiries.

The internationalization of small and medium‐sized businesses typically involves negotiation, agreement and exchange between business leaders from different national cultural values and traditions. Explores whether, and how, national values affect the strategic aims of business leaders, the content of their strategic deliberations, and the processes they follow to develop those ways of thinking into enacted strategies. The two business leaders studied were operating within the Standard Industrial Code 33.20/1, developing and combining electronic hardware and software technologies to address the needs of industrial customers world‐wide, but were from countries with different national values. The aims of the business leaders, and the processes they used to develop strategies differed, in ways which reflected their national backgrounds. The contents of the strategic issues they considered, however, were more similar, largely reflecting industry norms and demands, in these cases expressed on a global scale.

This paper makes an initial exploration of whether and to what extent different national values may affect the development of business relationships between individuals in different countries, by specifically examining the development of trust and co-operation between people. It first identifies key factors that may determine the nature and effect of trust in business relationships. Trust based on calculus, knowledge, and identification are distinguished. Inhibitions to co-operation are also identified, which include the perceptions of economic value, of social returns, of risk, and of competence of the potential co-operating parties. A model of trust formation and its impact on co-operation enabling detailed interpretation of empirical data is presented. Notions of national values developed in previous research are outlined, and a set of formal tabulated propositions regarding how these may be expected to influence different aspects of trust formation in different European countries is developed. The rel...

We outline a completely probabilistic study of travelling-wave solutions of the FKPP reaction-diffusion equation that are monotone and connect 0 to 1. The necessary asymptotics of such travelling-waves are proved using martingale and Brownian motion techniques. Recalling the connection between the FKPP equation and branching Brownian motion through the work of McKean and Neveu, we show how the necessary asymptotics and results about branching Brownian motion combine to give the existence and uniqueness of travelling waves of all speeds greater than or equal to the critical speed.

Let I be a countably infinite set of points in [open face R] which we can write as I={ui: i[set membership][open face Z]}, with ui

Background Invasive Non-typhoidal Salmonella (iNTS) are an important cause of bacteraemia in children and HIV-infected adults in sub-Saharan Africa. Previous research has shown that iNTS strains exhibit a pattern of gene loss that resembles that of host adapted serovars such as Salmonella Typhi and Paratyphi A. Salmonella enterica serovar Bovismorbificans was a common serovar in Malawi between 1997 and 2004. Methodology We sequenced the genomes of 14 Malawian bacteraemia and four veterinary isolates from the UK, to identify genomic variations and signs of host adaptation in the Malawian strains. Principal Findings Whole genome phylogeny of invasive and veterinary S. Bovismorbificans isolates showed that the isolates are highly related, belonging to the most common international S. Bovismorbificans Sequence Type, ST142, in contrast to the findings for S. Typhimurium, where a distinct Sequence Type, ST313, is associated with invasive disease in sub-Saharan Africa. Although genome degradation through pseudogene formation was observed in ST142 isolates, there were no clear overlaps with the patterns of gene loss seen in iNTS ST313 isolates previously described from Malawi, and no clear distinction between S. Bovismorbificans isolates from Malawi and the UK. The only defining differences between S. Bovismorbificans bacteraemia and veterinary isolates were prophage-related regions and the carriage of a S. Bovismorbificans virulence plasmid (pVIRBov). Conclusions iNTS S. Bovismorbificans isolates, unlike iNTS S. Typhiumrium isolates, are only distinguished from those circulating elsewhere by differences in the mobile genome. It is likely that these strains have entered a susceptible population and are able to take advantage of this niche. There are tentative signs of convergent evolution to a more human adapted iNTS variant. Considering its importance in causing disease in this region, S. Bovismorbificans may be at the beginning of this process, providing a reference against which to compare changes that may become fixed in future lineages in sub-Saharan Africa., Author Summary Bacteraemia and meningitis caused by non-typhoidal Salmonella (including serovars Typhimurium, Enteritidis and Bovismorbificans) are a serious health issue in sub-Saharan Africa, particularly in young children and HIV-infected adults. Previous work has indicated that a distinct S. Typhimurium sequence type, ST313, has evolved and spread in these countries, and may be more human-adapted than isolates found in the developed world. We therefore investigated the genomes of Salmonella enterica serovar Bovismorbificans bacteraemia isolates from Malawi and compared them to genomes of veterinary S. Bovismorbificans isolates from the UK using Next Generation Sequencing Technology and subsequent genomic comparisons to establish if there is a genetic basis for this increase in invasive disease observed among African NTS. Contrary to the previous findings for S. Typhimurium, where a distinct ST is found only in sub-Saharan Africa, we discovered that the S. Bovismorbificans isolates from Malawi belong to the most common ST of the serovar and the genome is highly conserved across all sequenced isolates. The major differences between UK veterinary and African human isolates were due to prophage regions inserted into the genomes of African isolates, coupled with a higher prevalence of a virulence plasmid compared to the UK isolates.

Salmonella enterica serovar Typhimurium definitive type 2 (DT2) is host restricted to Columba livia (rock or feral pigeon) but is also closely related to S. Typhimurium isolates that circulate in livestock and cause a zoonosis characterized by gastroenteritis in humans. DT2 isolates formed a distinct phylogenetic cluster within S. Typhimurium based on whole-genome-sequence polymorphisms. Comparative genome analysis of DT2 94-213 and S. Typhimurium SL1344, DT104, and D23580 identified few differences in gene content with the exception of variations within prophages. However, DT2 94-213 harbored 22 pseudogenes that were intact in other closely related S. Typhimurium strains. We report a novel in silico approach to identify single amino acid substitutions in proteins that have a high probability of a functional impact. One polymorphism identified using this method, a single-residue deletion in the Tar protein, abrogated chemotaxis to aspartate in vitro. DT2 94-213 also exhibited an altered transcriptional profile in response to culture at 42°C compared to that of SL1344. Such differentially regulated genes included a number involved in flagellum biosynthesis and motility., IMPORTANCE Whereas Salmonella enterica serovar Typhimurium can infect a wide range of animal species, some variants within this serovar exhibit a more limited host range and altered disease potential. Phylogenetic analysis based on whole-genome sequences can identify lineages associated with specific virulence traits, including host adaptation. This study represents one of the first to link pathogen-specific genetic signatures, including coding capacity, genome degradation, and transcriptional responses to host adaptation within a Salmonella serovar. We performed comparative genome analysis of reference and pigeon-adapted definitive type 2 (DT2) S. Typhimurium isolates alongside phenotypic and transcriptome analyses, to identify genetic signatures linked to host adaptation within the DT2 lineage.