Reconstructing the origin and evolution of land plants and their algal relatives is a fundamental problem in plant phylogenetics, and is essential for understanding how critical adaptations arose, including the embryo, vascular tissue, seeds, and flowers. Despite advances in molecular systematics, some hypotheses of relationships remain weakly resolved. Inferring deep phylogenies with bouts of rapid diversification can be problematic; however, genome-scale data should significantly increase the number of informative characters for analyses. Recent phylogenomic reconstructions focused on the major divergences of plants have resulted in promising but inconsistent results. One limitation is sparse taxon sampling, likely resulting from the difficulty and cost of data generation. To address this limitation, transcriptome data for 92 streptophyte taxa were generated and analyzed along with 11 published plant genome sequences. Phylogenetic reconstructions were conducted using up to 852 nuclear genes and 1,701,170 aligned sites. Sixty-nine analyses were performed to test the robustness of phylogenetic inferences to permutations of the data matrix or to phylogenetic method, including supermatrix, supertree, and coalescent-based approaches, maximum-likelihood and Bayesian methods, partitioned and unpartitioned analyses, and amino acid versus DNA alignments. Among other results, we find robust support for a sister-group relationship between land plants and one group of streptophyte green algae, the Zygnematophyceae. Strong and robust support for a clade comprising liverworts and mosses is inconsistent with a widely accepted view of early land plant evolution, and suggests that phylogenetic hypotheses used to understand the evolution of fundamental plant traits should be reevaluated.
The aim of the study was to investigate the prognostic value of right heart catheterisation variables measured during exercise. 55 incident patients with idiopathic, familial or anorexigen-associated pulmonary arterial hypertension (PAH) underwent right heart catheterisation at rest and during exercise and 6-min walk testing before PAH treatment initiation. Patients were treated according to recommendations within the next 2 weeks. Right heart catheterisation was repeated 3-5 months into the PAH treatment in 20 patients. Exercise cardiac index decreased gradually as New York Heart Association (NYHA) functional class increased whereas cardiac index at rest was not significantly different across NYHA groups. Baseline 6-min walk distance correlated significantly with exercise and change in cardiac index from rest to exercise (r=0.414 and r=0.481, respectively; p<0.01). Change in 6-min walk distance from baseline to 3-5 months under PAH treatment was highly correlated with change in exercise cardiac index (r=0.746, p<0.001). The most significant baseline covariates associated with survival were change in systolic pulmonary artery pressure from rest to exercise and exercise cardiac index (hazard ratio 0.56 (95% CI 0.37-0.86) and 0.14 (95% CI 0.05-0.43), respectively). Change in pulmonary haemodynamics during exercise is an important tool for assessing disease severity and may help devise optimal treat-to-target strategies.
Biofortification of rice (Oryza sativa L.) using a transgenic approach to increase the amount of iron in the grain is proposed as a low-cost, reliable, and sustainable solution to help developing countries combat anemia. In this study, we generated and evaluated a large number of rice or soybean ferritin over-accumulators in rice mega-variety IR64, including marker-free events, by introducing soybean or rice ferritin genes into the endosperm for product development. Accumulation of the protein was confirmed by ELISA, in situ immunological detection, and Western blotting. As much as a 37- and 19-fold increase in the expression of ferritin gene in single and co-transformed plants, respectively, and a 3.4-fold increase in Fe content in the grain over the IR64 wild type was achieved using this approach. Agronomic characteristics of a total of 1,860 progenies from 58 IR64 single independent transgenic events and 768 progenies from 27 marker-free transgenic events were evaluated and most trait characteristics did not show a penalty. Grain quality evaluation of high-Fe IR64 transgenic events showed quality similar to that of the wild-type IR64. To understand the effect of transgenes on iron homeostasis, transcript analysis was conducted on a subset of genes involved in iron uptake and loading. Gene expression of the exogenous ferritin gene in grain correlates with protein accumulation and iron concentration. The expression of NAS2 and NAS3 metal transporters increased during the grain milky stage.
Recent reports from pulmonary arterial hypertension (PAH) registries suggest that the mean age at diagnosis is increasing, outlining a growing proportion of elderly male patients. As a consequence, the classical description of the disease is shifting and may no more be described as a rare disease typically affecting young women. Potential explanations of this changing picture may include an aging of populations in western countries, the increase in life expectancy and the growing awareness of PAH and emergence of potential efficient treatments. Diagnostic workup of severe pulmonary hypertension (PH) in the elderly should be performed in such a way as to discriminate between the expected consequences of aging, pulmonary vascular disease, and other frequent causes of secondary PH (left heart failure or lung disease). Careful exploration by right heart catheterization is mandatory, but special attention should be paid to several pitfalls specific to this procedure in this age group. This is a matter of concern as clinical trials that aim to study new specific drug therapy for PAH might be biased by the inclusion of misdiagnosed patients. The aim of this review is to highlight the main difficulties in diagnosing PAH in the elderly and to propose a practical approach to distinguish PAH from the other frequent causes of PH in this population.
The intention of this editorial is to steer researchers through methodological choices in molecular evolution, drawing on the combined expertise of the authors. Our aim is not to review the most advanced methods for a specific task. Rather, we define several general guidelines to help with methodology choices at different stages of a typical phylogenetic pipeline. We are not able to provide exhaustive citation of a literature that is vast and plentiful, but we point the reader to a set of classical textbooks that reflect the state-of-the-art. We do not wish to appear overly critical of outdated methodology but rather provide some practical guidance on the sort of issues which should be considered. We stress that a reported study should be well-motivated and evaluate a specific hypothesis or scientific question. However, a publishable study should not be merely a compilation of available sequences for a protein family of interest followed by some standard analyses, unless it specifically addresses a scientific hypothesis or question. The rapid pace at which sequence data accumulate quickly outdates such publications. Although clearly, discoveries stemming from data mining, reports of new tools and databases and review papers are also desirable.
The contribution of heart rate (HR) to pulmonary artery hemodynamics has been suggested in pulmonary hypertension (PH). Our high-fidelity pressure, retrospective study tested the hypothesis that HR explained the majority of mean pulmonary artery pressure (mPAP) and pulse pressure (PApp) variation in 12 severe precapillary PH patients who performed incremental-load cycling while in the supine position. Seven idiopathic pulmonary arterial hypertension patients and five chronic thromboembolic PH patients were studied. Four to five PAP-thermodilution cardiac output (CO) points (mean: 4.4) were obtained. At rest, mPAP was 57 ± 9 mmHg, PApp was 51 ± 11 mmHg, HR was 90 ± 12 beats/min, and stroke volume (SV) was 50 ± 22 ml. At peak exercise, mPAP was 76 ± 10 mmHg, PApp was 67 ± 11 mmHg, and HR was 123 ± 18 beats/min (i.e., 71 ± 10% of maximum HR, each P < 0.05), whereas SV was 51 ± 20 ml (P = not significant). The input resistance did not change (mPAP/CO = 14.1 ± 4.1 vs. 13.5 ± 4.4 mmHg·min·l(-1)). The relative increase in mPAP was related to the relative increase in HR (n = 12, r(2) = 0.74) but not in CO. mPAP was linearly related to CO in 8 of 12 patients (median r(2) = 0.83) and to HR in 12 of 12 patients (median r(2) = 0.985). The parsimony principle favored the latter fit. PApp was linearly related to mPAP in 12 of 12 patients (median r(2) = 0.985), HR in 10 of 12 patients (median r(2) = 0.97), CO in 7 of 12 patients (median r(2) = 0.87), and SV in 1 of 12 patients. A strong linear relationship between HR and mPAP was consistently documented in severe precapillary PH patients who performed supine exercise. The limited value of thermodilution CO to predict mPAP could be explained by unavoidable precision errors in CO measurements, unchanged/decreased SV on exercise, curvilinearity of the mPAP-CO relationship at high flow, or flow-independent additional mechanisms increasing mPAP on exercise.
The mean pulmonary artery pressure (mPAP) replaces mean systolic ejection pressure (msePAP) in the classic formula of right ventricular stroke work (RVSW) = (mPAP - RAP) × stroke volume, where RAP is mean right atrial pressure. Only the steady work is thus taken into account, not the pulsatile work, whereas pulmonary circulation is highly pulsatile. Our retrospective, high-fidelity pressure study tested the hypothesis that msePAP was proportional to mPAP, and looked at the implications for RVSW.
Ventricular-arterial coupling is a measure of the relationship between ventricular contractility and afterload. We sought to determine the relationship between ventricular-arterial coupling and right ventricular (RV) remodeling in a novel porcine model of progressive pulmonary hypertension (PH).
The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
Cnidaria (corals, sea anemones, hydroids, jellyfish) is a phylum of relatively simple aquatic animals characterized by the presence of the cnidocyst: a cell containing a giant capsular organelle with an eversible tubule (cnida). Species within Cnidaria have life cycles that involve one or both of the two distinct body forms, a typically benthic polyp, which may or may not be colonial, and a typically pelagic mostly solitary medusa. The currently accepted taxonomic scheme subdivides Cnidaria into two main assemblages: Anthozoa (Hexacorallia?+?Octocorallia) - cnidarians with a reproductive polyp and the absence of a medusa stage - and Medusozoa (Cubozoa, Hydrozoa, Scyphozoa, Staurozoa) - cnidarians that usually possess a reproductive medusa stage. Hypothesized relationships among these taxa greatly impact interpretations of cnidarian character evolution.
Contradicting the prejudice that endosymbiosis is a rare phenomenon, Husník and co-workers show in BMC Biology that bacterial endosymbiosis has occured several times independently during insect evolution. Rigorous phylogenetic analyses, in particular using complex models of sequence evolution and an original site removal procedure, allow this conclusion to be established after eschewing inference artefacts that usually plague the positioning of highly divergent endosymbiont genomic sequences.
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by lung endothelial dysfunction and vascular remodeling. Recently, bone marrow progenitor cells have been localized to PAH lungs, raising the question of their role in disease progression. Independently, serotonin (5-HT) and its receptors have been identified as contributors to the PAH pathogenesis. We hypothesized that 1 of these receptors, 5-HT(2B), is involved in bone marrow stem cell mobilization that participates in the development of PAH and pulmonary vascular remodeling. A first study revealed expression of 5-HT(2B) receptors by circulating c-kit(+) precursor cells, whereas mice lacking 5-HT(2B) receptors showed alterations in platelets and monocyte-macrophage numbers, and in myeloid lineages of bone marrow. Strikingly, mice with restricted expression of 5-HT(2B) receptors in bone marrow cells developed hypoxia or monocrotaline-induced increase in pulmonary pressure and vascular remodeling, whereas restricted elimination of 5-HT(2B) receptors on bone marrow cells confers a complete resistance. Moreover, ex vivo culture of human CD34(+) or mice c-kit(+) progenitor cells in the presence of a 5-HT(2B) receptor antagonist resulted in altered myeloid differentiation potential. Thus, we demonstrate that activation of 5-HT(2B) receptors on bone marrow lineage progenitors is critical for the development of PAH.
Morphological data traditionally group Tardigrada (water bears), Onychophora (velvet worms), and Arthropoda (e.g., spiders, insects, and their allies) into a monophyletic group of invertebrates with walking appendages known as the Panarthropoda. However, molecular data generally do not support the inclusion of tardigrades within the Panarthropoda, but instead place them closer to Nematoda (roundworms). Here we present results from the analyses of two independent genomic datasets, expressed sequence tags (ESTs) and microRNAs (miRNAs), which congruently resolve the phylogenetic relationships of Tardigrada. Our EST analyses, based on 49,023 amino acid sites from 255 proteins, significantly support a monophyletic Panarthropoda including Tardigrada and suggest a sister group relationship between Arthropoda and Onychophora. Using careful experimental manipulations--comparisons of model fit, signal dissection, and taxonomic pruning--we show that support for a Tardigrada + Nematoda group derives from the phylogenetic artifact of long-branch attraction. Our small RNA libraries fully support our EST results; no miRNAs were found to link Tardigrada and Nematoda, whereas all panarthropods were found to share one unique miRNA (miR-276). In addition, Onychophora and Arthropoda were found to share a second miRNA (miR-305). Our study confirms the monophyly of the legged ecdysozoans, shows that past support for a Tardigrada + Nematoda group was due to long-branch attraction, and suggests that the velvet worms are the sister group to the arthropods.
The normal mean pulmonary artery pressure (PAP) is 14 ± 3 mmHg. Precapillary pulmonary hypertension is defined as a mean PAP ? 25 mmHg at rest and a pulmonary capillary wedge pressure ? 15 mmHg as assessed by right heart catheterization. When performed in experienced centers, right heart catheter procedures in patients with pulmonary hypertension are associated with low morbidity and mortality rates. Right heart catheterization remains essential for the management of pulmonary arterial hypertension (PAH) as it confirms the diagnosis, determines the type of pulmonary hypertension, its severity, its vasoreactivity as well as response to therapeutic interventions. The hemodynamic severity largely influences patients management including the choice of initial and subsequent therapies. Hemodynamic evaluation during exercise allows a precise characterization of the true resistive properties of pulmonary vessels through the assessment of the pressure-flow relationship. The significance of isolated pulmonary hypertension during exercise remains unknown. Indeed, roughly 50% of healthy subjects > 50 years old exhibit mean PAP > 30 mmHg during mild exercise. Isolated exercise-induced increases in mean PAP > 30 mmHg during exercise is thus no longer used to define pulmonary hypertension. More complex hemodynamic parameters allow partitioning of arterial and venous vascular resistance, as well as a better characterization of pulmonary artery compliance, right ventricle function and right ventriculo-arterial coupling. The clinical relevance of these subtle markers of pulmonary vascular abnormalities remains unknown.
The terrestrial habitat was colonized by the ancestors of modern land plants about 500 to 470 million years ago. Today it is widely accepted that land plants (embryophytes) evolved from streptophyte algae, also referred to as charophycean algae. The streptophyte algae are a paraphyletic group of green algae, ranging from unicellular flagellates to morphologically complex forms such as the stoneworts (Charales). For a better understanding of the evolution of land plants, it is of prime importance to identify the streptophyte algae that are the sister-group to the embryophytes. The Charales, the Coleochaetales or more recently the Zygnematales have been considered to be the sister group of the embryophytes However, despite many years of phylogenetic studies, this question has not been resolved and remains controversial.
Xenoturbellida and Acoelomorpha are marine worms with contentious ancestry. Both were originally associated with the flatworms (Platyhelminthes), but molecular data have revised their phylogenetic positions, generally linking Xenoturbellida to the deuterostomes and positioning the Acoelomorpha as the most basally branching bilaterian group(s). Recent phylogenomic data suggested that Xenoturbellida and Acoelomorpha are sister taxa and together constitute an early branch of Bilateria. Here we assemble three independent data sets-mitochondrial genes, a phylogenomic data set of 38,330 amino-acid positions and new microRNA (miRNA) complements-and show that the position of Acoelomorpha is strongly affected by a long-branch attraction (LBA) artefact. When we minimize LBA we find consistent support for a position of both acoelomorphs and Xenoturbella within the deuterostomes. The most likely phylogeny links Xenoturbella and Acoelomorpha in a clade we call Xenacoelomorpha. The Xenacoelomorpha is the sister group of the Ambulacraria (hemichordates and echinoderms). We show that analyses of miRNA complements have been affected by character loss in the acoels and that both groups possess one miRNA and the gene Rsb66 otherwise specific to deuterostomes. In addition, Xenoturbella shares one miRNA with the ambulacrarians, and two with the acoels. This phylogeny makes sense of the shared characteristics of Xenoturbellida and Acoelomorpha, such as ciliary ultrastructure and diffuse nervous system, and implies the loss of various deuterostome characters in the Xenacoelomorpha including coelomic cavities, through gut and gill slits.
Model violations constitute the major limitation in inferring accurate phylogenies. Characterizing properties of the data that are not being correctly handled by current models is therefore of prime importance. One of the properties of protein evolution is the variation of the relative rate of substitutions across sites and over time, the latter is the phenomenon called heterotachy. Its effect on phylogenetic inference has recently obtained considerable attention, which led to the development of new models of sequence evolution. However, thus far focus has been on the quantitative heterogeneity of the evolutionary process, thereby overlooking more qualitative variations.
Genomes of animals as different as sponges and humans show conservation of global architecture. Here we show that multiple genomic features including transposon diversity, developmental gene repertoire, physical gene order, and intron-exon organization are shattered in the tunicate Oikopleura, belonging to the sister group of vertebrates and retaining chordate morphology. Ancestral architecture of animal genomes can be deeply modified and may therefore be largely nonadaptive. This rapidly evolving animal lineage thus offers unique perspectives on the level of genome plasticity. It also illuminates issues as fundamental as the mechanisms of intron gain.
While a unique origin of the euarthropods is well established, relationships between the four euarthropod classes-chelicerates, myriapods, crustaceans and hexapods-are less clear. Unsolved questions include the position of myriapods, the monophyletic origin of chelicerates, and the validity of the close relationship of euarthropods to tardigrades and onychophorans. Morphology predicts that myriapods, insects and crustaceans form a monophyletic group, the Mandibulata, which has been contradicted by many molecular studies that support an alternative Myriochelata hypothesis (Myriapoda plus Chelicerata). Because of the conflicting insights from published molecular datasets, evidence from nuclear-coding genes needs corroboration from independent data to define the relationships among major nodes in the euarthropod tree. Here, we address this issue by analysing two independent molecular datasets: a phylogenomic dataset of 198 protein-coding genes including new sequences for myriapods, and novel microRNA complements sampled from all major arthropod lineages. Our phylogenomic analyses strongly support Mandibulata, and show that Myriochelata is a tree-reconstruction artefact caused by saturation and long-branch attraction. The analysis of the microRNA dataset corroborates the Mandibulata, showing that the microRNAs miR-965 and miR-282 are present and expressed in all mandibulate species sampled, but not in the chelicerates. Mandibulata is further supported by the phylogenetic analysis of a comprehensive morphological dataset covering living and fossil arthropods, and including recently proposed, putative apomorphies of Myriochelata. Our phylogenomic analyses also provide strong support for the inclusion of pycnogonids in a monophyletic Chelicerata, a paraphyletic Cycloneuralia, and a common origin of Arthropoda (tardigrades, onychophorans and arthropods), suggesting that previous phylogenies grouping tardigrades and nematodes may also have been subject to tree-reconstruction artefacts.
According to the chromalveolate hypothesis (Cavalier-Smith T. 1999. Principles of protein and lipid targeting in secondary symbiogenesis: euglenoid, dinoflagellate, and sporozoan plastid origins and the eukaryote family tree. J Eukaryot Microbiol 46:347-366), the four eukaryotic groups with chlorophyll c-containing plastids originate from a single photosynthetic ancestor, which acquired its plastids by secondary endosymbiosis with a red alga. So far, molecular phylogenies have failed to either support or disprove this view. Here, we devise a phylogenomic falsification of the chromalveolate hypothesis that estimates signal strength across the three genomic compartments: If the four chlorophyll c-containing lineages indeed derive from a single photosynthetic ancestor, then similar amounts of plastid, mitochondrial, and nuclear sequences should allow to recover their monophyly. Our results refute this prediction, with statistical support levels too different to be explained by evolutionary rate variation, phylogenetic artifacts, or endosymbiotic gene transfer. Therefore, we reject the chromalveolate hypothesis as falsified in favor of more complex evolutionary scenarios involving multiple higher order eukaryote-eukaryote endosymbioses.
Modeling the interplay between mutation and selection at the molecular level is key to evolutionary studies. To this end, codon-based evolutionary models have been proposed as pertinent means of studying long-range evolutionary patterns and are widely used. However, these approaches have not yet consolidated results from amino acid level phylogenetic studies showing that selection acting on proteins displays strong site-specific effects, which translate into heterogeneous amino acid propensities across the columns of alignments; related codon-level studies have instead focused on either modeling a single selective context for all codon columns, or a separate selective context for each codon column, with the former strategy deemed too simplistic and the latter deemed overparameterized. Here, we integrate recent developments in nonparametric statistical approaches to propose a probabilistic model that accounts for the heterogeneity of amino acid fitness profiles across the coding positions of a gene. We apply the model to a dozen real protein-coding gene alignments and find it to produce biologically plausible inferences, for instance, as pertaining to site-specific amino acid constraints, as well as distributions of scaled selection coefficients. In their account of mutational features as well as the heterogeneous regimes of selection at the amino acid level, the modeling approaches studied here can form a backdrop for several extensions, accounting for other selective features, for variable population size, or for subtleties of mutational features, all with parameterizations couched within population-genetic theory.
Assessing the influence of three-dimensional protein structure on sequence evolution is a difficult task, mainly because of the assumption of independence between sites required by probabilistic phylogenetic methods. Recently, models that include an explicit treatment of protein structure and site interdependencies have been developed: a statistical potential (an energy-like scoring system for sequence-structure compatibility) is used to evaluate the probability of fixation of a given mutation, assuming a coarse-grained protein structure that is constant through evolution. Yet, due to the novelty of these models and the small degree of overlap between the fields of structural and evolutionary biology, only simple representations of protein structure have been used so far. In this work, we present new forms of statistical potentials using a probabilistic framework recently developed for evolutionary studies. Terms related to pairwise distance interactions, torsion angles, solvent accessibility, and flexibility of the residues are included in the potentials, so as to study the effects of the main factors known to influence protein structure. The new potentials, with a more detailed representation of the protein structure, yield a better fit than the previously used scoring functions, with pairwise interactions contributing to more than half of this improvement. In a phylogenetic context, however, the structurally constrained models are still outperformed by some of the available site-independent models in terms of fit, possibly indicating that alternatives to coarse-grained statistical potentials should be explored in order to better model structural constraints.
The physical sciences have long recognized the distinction between formal descriptions of observations versus explanations for observations, with the canonical example embodied in the axiom statistical mechanics explains thermodynamics. Descriptive models are often said to be phenomenologically motivated whereas explanatory models are said to be mechanistically motivated. In molecular evolutionary modeling the two approaches can typically be classified as dealing with either the inference of phylogenies - the phenomenological approach, lacking particular interest in evolutionary mechanisms per se, or focused on explaining the evolutionary process itself - the mechanistic approach. Here we emphasize that both phenomenological and mechanistic approaches are inherently present in any model. Focusing on the field of codon substitution modeling we point out that this area, traditionally viewed as being mechanistically motivated, has itself been imbued with phenomenological underpinnings. Using practical examples we stress that clarifying phenomenological and mechanistic motivations can help guide model developments, and suggest future work directions.
Horizontal gene transfer (HGT) is one of the main mechanisms driving the evolution of microorganisms. Its accurate identification is one of the major challenges posed by reticulate evolution. In this article, we describe a new polynomial-time algorithm for inferring HGT events and compare 3 existing and 1 new tree comparison indices in the context of HGT identification. The proposed algorithm can rely on different optimization criteria, including least squares (LS), Robinson and Foulds (RF) distance, quartet distance (QD), and bipartition dissimilarity (BD), when searching for an optimal scenario of subtree prune and regraft (SPR) moves needed to transform the given species tree into the given gene tree. As the simulation results suggest, the algorithmic strategy based on BD, introduced in this article, generally provides better results than those based on LS, RF, and QD. The BD-based algorithm also proved to be more accurate and faster than a well-known polynomial time heuristic RIATA-HGT. Moreover, the HGT recovery results yielded by BD were generally equivalent to those provided by the exponential-time algorithm LatTrans, but a clear gain in running time was obtained using the new algorithm. Finally, a statistical framework for assessing the reliability of obtained HGTs by bootstrap analysis is also presented.
Heterotachy, the variation of substitution rate at a site across time, is a prevalent phenomenon in nucleotide and amino acid alignments, which may mislead probabilistic-based phylogenetic inferences. The covarion model is a special case of heterotachy, in which sites change between the "ON" state (allowing substitutions according to any particular model of sequence evolution) and the "OFF" state (prohibiting substitutions). In current implementations, the switch rates between ON and OFF states are homogeneous across sites, a hypothesis that has never been tested. In this study, we developed an infinite mixture model, called the covarion mixture (CM) model, which allows the covarion parameters to vary across sites, controlled by a Dirichlet process prior. Moreover, we combine the CM model with other approaches. We use a second independent Dirichlet process that models the heterogeneities of amino acid equilibrium frequencies across sites, known as the CAT model, and general rate-across-site heterogeneity is modeled by a gamma distribution. The application of the CM model to several large alignments demonstrates that the covarion parameters are significantly heterogeneous across sites. We describe posterior predictive discrepancy tests and use these to demonstrate the importance of these different elements of the models.
Resolving the evolutionary relationships among Fungi remains challenging because of their highly variable evolutionary rates, and lack of a close phylogenetic outgroup. Nucleariida, an enigmatic group of amoeboids, have been proposed to emerge close to the fungal-metazoan divergence and might fulfill this role. Yet, published phylogenies with up to five genes are without compelling statistical support, and genome-level data should be used to resolve this question with confidence.
In recent years, molecular evolutionary models formulated as site-interdependent Markovian codon substitution processes have been proposed as means of mechanistically accounting for selective features over long-range evolutionary scales. Under such models, site interdependencies are reflected in the use of a simplified protein tertiary structure representation and predefined statistical potential, which, along with mutational parameters, mediate nonsynonymous rates of substitution; rates of synonymous events are solely mediated by mutational parameters. Although theoretically attractive, the models are computationally challenging, and the methods used to manipulate them still do not allow for quantitative model evaluations in a multiple-sequence context. Here, we describe Markov chain Monte Carlo computational methodologies for sampling parameters from their posterior distribution under site-interdependent codon substitution models within a phylogenetic context and allowing for Bayesian model assessment and ranking. Specifically, the techniques we expound here can form the basis of posterior predictive checking under these models and can be embedded within thermodynamic integration algorithms for computing Bayes factors. We illustrate the methods using two data sets and find that although current forms of site-interdependent models of codon substitution provide an improved fit, they are outperformed by the extended site-independent versions. Altogether, the methodologies described here should enable a quantified contrasting of alternative ways of modeling structural constraints, or other site-interdependent criteria, and establish if such formulations can match (or supplant) site-independent model extensions.
Mean pulmonary artery pressure (mPAP) may be estimated by using the classic rule of thumb, namely 2/3 x dPAP + 1/3 x sPAP, where dPAP = diastolic PAP and sPAP = systolic PAP. Studies have suggested that mPAP may be also estimated from sPAP alone. Pulmonary hypertension (PH) is usually defined by an invasive mPAP > 25 mm Hg, but the corresponding sPAP threshold remains to be established. Our study evaluated the accuracy and precision of various empirical formulas relating mPAP and sPAP in resting adults.
The origin of many of the defining features of animal body plans, such as symmetry, nervous system, and the mesoderm, remains shrouded in mystery because of major uncertainty regarding the emergence order of the early branching taxa: the sponge groups, ctenophores, placozoans, cnidarians, and bilaterians. The "phylogenomic" approach  has recently provided a robust picture for intrabilaterian relationships [2, 3] but not yet for more early branching metazoan clades. We have assembled a comprehensive 128 gene data set including newly generated sequence data from ctenophores, cnidarians, and all four main sponge groups. The resulting phylogeny yields two significant conclusions reviving old views that have been challenged in the molecular era: (1) that the sponges (Porifera) are monophyletic and not paraphyletic as repeatedly proposed [4-9], thus undermining the idea that ancestral metazoans had a sponge-like body plan; (2) that the most likely position for the ctenophores is together with the cnidarians in a "coelenterate" clade. The Porifera and the Placozoa branch basally with respect to a moderately supported "eumetazoan" clade containing the three taxa with nervous system and muscle cells (Cnidaria, Ctenophora, and Bilateria). This new phylogeny provides a stimulating framework for exploring the important changes that shaped the body plans of the early diverging phyla.
Chronic thromboembolic pulmonary hypertension is due to partial obstruction of the pulmonary arterial bed and may resolve after pulmonary thromboendarterectomy. Persistent pulmonary hypertension, the main complication after pulmonary thromboendarterectomy, may reflect vessel alterations induced by high flow in unobstructed lung territories. The aim of this study was to determine whether correcting high flow led to reversal of the vasculopathy in piglets.
Several morphologically dissimilar ascomycete fungi including Schizosaccharomyces, Taphrina, Saitoella, Pneumocystis, and Neolecta have been grouped into the taxon Taphrinomycotina (Archiascomycota or Archiascomycotina), originally based on rRNA phylogeny. These analyses lack statistically significant support for the monophyly of this grouping, and although confirmed by more recent multigene analyses, this topology is contradicted by mitochondrial phylogenies. To resolve this inconsistency, we have assembled phylogenomic mitochondrial and nuclear data sets from four distantly related taphrinomycotina taxa: Schizosaccharomyces pombe, Pneumocystis carinii, Saitoella complicata, and Taphrina deformans. Our phylogenomic analyses based on nuclear data (113 proteins) conclusively support the monophyly of Taphrinomycotina, diverging as a sister group to Saccharomycotina + Pezizomycotina. However, despite the improved taxon sampling, Taphrinomycotina continue to be paraphyletic with the mitochondrial data set (13 proteins): Schizosaccharomyces species associate with budding yeasts (Saccharomycotina) and the other Taphrinomycotina group as a sister group to Saccharomycotina + Pezizomycotina. Yet, as Schizosaccharomyces and Saccharomycotina species are fast evolving, the mitochondrial phylogeny may be influenced by a long-branch attraction (LBA) artifact. After removal of fast-evolving sequence positions from the mitochondrial data set, we recover the monophyly of Taphrinomycotina. Our combined results suggest that Taphrinomycotina is a legitimate taxon, that this group of species diverges as a sister group to Saccharomycotina + Pezizomycotina, and that phylogenetic positioning of yeasts and fission yeasts with mitochondrial data is plagued by a strong LBA artifact.
Phylogenomic analyses of ancient relationships are usually performed using amino acid data, but it is unclear whether amino acids or nucleotides should be preferred. With the 2-fold aim of addressing this problem and clarifying pancrustacean relationships, we explored the signals in the 62 protein-coding genes carefully assembled by Regier et al. in 2010. With reference to the pancrustaceans, this data set infers a highly supported nucleotide tree that is substantially different to the corresponding, but poorly supported, amino acid one. We show that the discrepancy between the nucleotide-based and the amino acids-based trees is caused by substitutions within synonymous codon families (especially those of serine-TCN and AGY). We show that different arthropod lineages are differentially biased in their usage of serine, arginine, and leucine synonymous codons, and that the serine bias is correlated with the topology derived from the nucleotides, but not the amino acids. We suggest that a parallel, partially compositionally driven, synonymous codon-usage bias affects the nucleotide topology. As substitutions between serine codon families can proceed through threonine or cysteine intermediates, amino acid data sets might also be affected by the serine codon-usage bias. We suggest that a Dayhoff recoding strategy would partially ameliorate the effects of such bias. Although amino acids provide an alternative hypothesis of pancrustacean relationships, neither the nucleotides nor the amino acids version of this data set seems to bring enough genuine phylogenetic information to robustly resolve the relationships within group, which should still be considered unresolved.
Progress in sequencing technology allows researchers to assemble ever-larger supermatrices for phylogenomic inference. However, current phylogenomic studies often rest on patchy data sets, with some having 80% missing (or ambiguous) data or more. Though early simulations had suggested that missing data per se do not harm phylogenetic inference when using sufficiently large data sets, Lemmon et al. (Lemmon AR, Brown JM, Stanger-Hall K, Lemmon EM. 2009. The effect of ambiguous data on phylogenetic estimates obtained by maximum likelihood and Bayesian inference. Syst Biol. 58:130-145.) have recently cast doubt on this consensus in a study based on the introduction of parsimony-uninformative incomplete characters. In this work, we empirically reassess the issue of missing data in phylogenomics while exploring possible interactions with the model of sequence evolution. First, we note that parsimony-uninformative incomplete characters are actually informative in a probabilistic framework. A reanalysis of Lemmons data set with this in mind gives a very different interpretation of their results and shows that some of their conclusions may be unfounded. Second, we investigate the effect of the progressive introduction of missing data in a complete supermatrix (126 genes × 39 species) capable of resolving animal relationships. These analyses demonstrate that missing data perturb phylogenetic inference slightly beyond the expected decrease in resolving power. In particular, they exacerbate systematic errors by reducing the number of species effectively available for the detection of multiple substitutions. Consequently, large sparse supermatrices are more sensitive to phylogenetic artifacts than smaller but less incomplete data sets, which argue for experimental designs aimed at collecting a modest number (~50) of highly covered genes. Our results further confirm that including incomplete yet short-branch taxa (i.e., slowly evolving species or close outgroups) can help to eschew artifacts, as predicted by simulations. Finally, it appears that selecting an adequate model of sequence evolution (e.g., the site-heterogeneous CAT model instead of the site-homogeneous WAG model) is more beneficial to phylogenetic accuracy than reducing the level of missing data.
The study objective was to determine whether the vasculopathy seen in nonobstructed lung regions in chronic thromboembolic pulmonary hypertension is induced by the local blood flow increase or by factors released by the ischemic lung.
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