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New hypotheses on the material nature of horizontally mobile genes.

The evolutionary history of organisms is often assumed to be recorded in the structure of important molecules, such as DNA sequences. Whereas the structure of these molecules does sometimes affirm other evidence of ancestry, like fossil records, it sometimes does not. Horizontal gene transfer can distort perceptions of ancestry. Determining the impact of horizontal gene transfer on evolution has been limited by the crude tools available to detect it. Physical and genetic vectors are now known to conduct genes between organisms, even between biological kingdoms of organisms. The effects are being noticed in important molecules preserved in the genomes of organisms. This article will review the systematic bias in using molecular morphology, like DNA sequences, to infer ancestry and how this bias is the unavoidable result of the way that experimental genetics itself evolved. We present the novel hypothesis that genes usually called epigenes, like methylation patterns and prions, are infectiously transferred, sometimes using DNA as a vector, but not as a gene.

Biological Evolution↗

Probing the relationships of the branchiopod crustaceans.

The Branchiopoda display extraordinary variation in body form, even within the morphologically diverse crustaceans. To fully understand the origin and evolution of these morphological reconfigurations, a robust phylogeny of the group is essential. To infer the affinities among branchiopods, we employed two approaches to taxon and gene sampling, presented new sequence data from three genes, incorporated previously published sequence data from three additional genes, and utilized comprehensive techniques of phylogeny reconstruction. The results provided support for a number of longstanding hypotheses concerning the relationships among the orders. For example, we obtained support for the Cladoceromorpha and Gymnomera, and favoured a unique arrangement of the cladoceran orders. A few affinities remain to be resolved, particularly at the base of the Phyllopoda and within the Anomopoda. However, the results suggest that increased gene sampling is recommended for future investigations of branchiopod systematics.

Animals↗

Variation and evolution of biomolecular systems: searching for functional relevance.

The availability of genome sequences and functional genomics data from multiple species enables us to compare the composition of biomolecular systems like biochemical pathways and protein complexes between species. Here, we review small- and large-scale, "genomics-based" approaches to biomolecular systems variation. In general, caution is required when comparing the results of bioinformatics analyses of genomes or of functional genomics data between species. Limitations to the sensitivity of sequence analysis tools and the noisy nature of genomics data tend to lead to systematic overestimates of the amount of variation. Nevertheless, the results from detailed manual analyses, and of large-scale analyses that filter out systematic biases, point to a large amount of variation in the composition of biomolecular systems. Such observations challenge our understanding of the function of the systems and their individual components and can potentially facilitate the identification and functional characterization of sub-systems within a system. Mapping the inter-species variation of complex biomolecular systems on a phylogenetic species tree allows one to reconstruct their evolution.

Evolution, Molecular↗

Organic syntheses from CH4-N2 atmospheres: implications for Titan.

Numerous experiments have already been performed, simulating the evolution of gaseous mixtures containing CH4 when submitted to energy flux. From their results, it appears that a variety of organic compounds, including unsaturated hydrocarbons and nitriles such as HCN, can be synthesized into noticeable amounts from CH4-N2 mixtures. In particular, systematic studies of the influence of the composition of the mixture on the nature and amount of synthesized compounds show that organic volatile nitriles, and particularly cyanoacetylene and cyanogen, are formed only in media rich in nitrogen. Those nitriles have been identified very recently in the atmosphere of Titan, and thus, data from such laboratory experiments may provide important indirect information on the organic chemistry occurring at the periphery of this satellite of Saturn. However, during these experiments, there is a continuous formation and accumulation of molecular hydrogen, which does not occur in the atmosphere of Titan, because of H2 escape. In order to reassess the data already available from this type of laboratory studies, experiments on CH4-N2 atmospheres, with and without H2 escape, have been recently performed. The influence of this parameter on the chemical evolution of the atmosphere and on the nature and relative quantities of organic compounds has been studied. After reviewing these experiments, implications of the obtained results on the organic chemistry at the periphery of Titan are discussed.

Chemical Phenomena↗

The evolutionary inheritance of elemental stoichiometry in marine phytoplankton.

Phytoplankton is a nineteenth century ecological construct for a biologically diverse group of pelagic photoautotrophs that share common metabolic functions but not evolutionary histories. In contrast to terrestrial plants, a major schism occurred in the evolution of the eukaryotic phytoplankton that gave rise to two major plastid superfamilies. The green superfamily appropriated chlorophyll b, whereas the red superfamily uses chlorophyll c as an accessory photosynthetic pigment. Fossil evidence suggests that the green superfamily dominated Palaeozoic oceans. However, after the end-Permian extinction, members of the red superfamily rose to ecological prominence. The processes responsible for this shift are obscure. Here we present an analysis of major nutrients and trace elements in 15 species of marine phytoplankton from the two superfamilies. Our results indicate that there are systematic phylogenetic differences in the two plastid types where macronutrient (carbon:nitrogen:phosphorus) stoichiometries primarily reflect ancestral pre-symbiotic host cell phenotypes, but trace element composition reflects differences in the acquired plastids. The compositional differences between the two plastid superfamilies suggest that changes in ocean redox state strongly influenced the evolution and selection of eukaryotic phytoplankton since the Proterozoic era.

Biological Evolution↗

[Animals (Animalia) in system of organisms. 2. Phylogenetic understanding of animals].

The development of systematics in last decade has shown that typological classifications of five-six Kingdoms is not adequate for describing the diversity of organisms. Information from the sequences of small subunit rRNA is not sufficient to reconstruct the position of eukaryotes on the phylogenetic tree due to the effect of long branches. Totally new reconstruction of eukaryotic phylogeny was built upon the analysis of many new molecular markers. Evolution of eukaryotes had two mainstreams. One has been connected with diversification of ancestral biciliate forms (Bikonta). Sister-group of Bikonta (Unikonta) includes some originally uniciliate amoebae and moulds (Amoebozoa), and uniciliate eukaryotes with posterior cilium (Opisthokonta). The taxon Opisthokonta unites Fungi, Nuclearimorpha, Mesomycetozoa, Choanozoa and Metazoa. The latter three groups or only Metazoa are attributes to animals. The following differentiation of the groups used in systematic for the description of diversity of organisms is proposed. (1) Taxon is a group which is defined on the basis of ancestry: taxon includes all species descended from one ancestor. Taxon differs from logic classes of typology at an ontologic level. Taxon arises and exists, and its composition and occupied niches can constantly change; taxon can flourish or, on the contrary, fade up to full disappearance. Thus, the predicative characteristic of taxon, including characters which are considered significant, are not absolute. It is significant only at the moment of consideration. But characters (synapomorphies) are important as the practical tool for discerning taxa at given time period. Taxa unite species into unique classification. This understanding of taxon corresponds to monophyletic group sensu Willi Hennig. (2) Class of organisms is a group which is defined on the basis of characters: class includes all species having the given character. The class is only a logic object. Unlike taxa grouping species into classes may be through different and crossed classifications. Inside the given category of groups it is possible to distinguish: (2.1) Level of the organization (grade) described by the differences on the levels of organization: for example prokaryotic and eukaryotic levels of the organization. Eukaryotes can be divided into unicellular (Protoctista, Protista) and multicelluar (tissue-specific-Histonia) forms. (2.2) Types of the organization distinguishing groups of one level: for example, amoedoid type (Sarcodina), naked (Gymnamoebia), and testate (Testacea) amoebas. (2.3) Taxonomic groups as set-theoretical approximations of taxa. (2.4) Groups of the mixed nature. For example, Haeckel has recognized Protophyta and Protozoa describing the unicellular level of the organization inside plants and animals accordingly. Protozoa in Cavalier-Smith's system (2002, 2004) is also an example of groups of the mixed nature.

Animal Population Groups↗

The evolution of human anti-double-stranded DNA autoantibodies.

It has been proposed that the anti-double-stranded DNA (dsDNA) response in patients with systemic lupus erythematosus (SLE) is antigen driven and that DNA or nucleosomes select anti-DNA reactive, somatically mutated B cells. We have used site-directed mutagenesis to systematically revert the somatic mutations of two human anti-dsDNA antibodies from SLE patients to analyze the resulting changes in DNA binding as well as binding to other autoantigens. Our data demonstrate that high-affinity binding to dsDNA and nucleosomes is acquired by somatic replacement mutations in a stepwise manner. Reactivity to surface structures of apoptotic cells is acquired by the same somatic mutations that generate high-affinity dsDNA binding. Importantly, revertant antibodies with germ-line V regions did not show any measurable DNA reactivity. We propose that anti-DNA autoantibodies are generated from nonautoreactive B cells during a normal immune response. B cells may acquire autoreactivity de novo during the process of somatic hypermutation. Nucleosomes, if available in lupus patients because of defects in clearing of apoptotic debris, might subsequently positively select high affinity anti-DNA B cells.

Amino Acid Sequence↗

In-depth analysis of a heterosexually acquired human immunodeficiency virus type 1 superinfection: evolution, temporal fluctuation, and intercompartment dynamics from the seronegative window period through 30 months postinfection.

Human immunodeficiency virus type 1 (HIV-1) superinfection refers to the acquisition of another strain by an already infected individual. Here we report a comprehensive genetic analysis of an HIV-1 superinfection acquired heterosexually. The infected individual was in a high-risk cohort in Tanzania, was exposed to multiple subtypes, and was systematically evaluated every 3 months with a fluorescent multi-region genotyping assay. The subject was identified in the window period and was first infected with a complex ACD recombinant strain, became superinfected 6 to 9 months later with an AC recombinant, and was monitored for >2.5 years. The plasma viral load exceeded 400,000 copies/ml during the first 9 months of infection but resolved to the set point of 67,000 copies/ml by 3 months after superinfection; the CD4 cell count was 377 cells/mul at 30 months. Viral diversity was evaluated with techniques designed to fully sample the quasi-species, permitting direct observation of the evolution, temporal fluctuation, and intercompartment dynamics of the initial and superinfecting strains and recombinants derived from them. Within 3 months of superinfection, seven different molecular forms were detected in gag and six were detected in env. The proportions of forms fluctuated widely over time in plasma and peripheral blood mononuclear cells, illustrating how challenging the detection of dually infected individuals can be. Strain-specific nested PCR confirmed that the superinfecting strain was not present until the 9 month follow-up. This study further defines the parameters and dynamics of superinfection and will foster appropriate studies and approaches to gain a more complete understanding of risk factors for superinfection and its impact on clinical progression, epidemiology, and vaccine design.

Evolution, Molecular↗

GEMDOCK: a generic evolutionary method for molecular docking.

We have developed an evolutionary approach for flexible ligand docking. This approval, GEMDOCK, uses a Generic Evolutionary Method for molecular DOCKing and an empirical scoring function. The former combines both discrete and continuous global search strategies with local search strategies to speed up convergence, whereas the latter results in rapid recognition of potential ligands. GEMDOCK was tested on a diverse data set of 100 protein-ligand complexes from the Protein Data Bank. In 79% of these complexes, the docked lowest energy ligand structures had root-mean-square derivations (RMSDs) below 2.0 A with respect to the corresponding crystal structures. The success rate increased to 85% if the structure water molecules were retained. We evaluated GEMDOCK on two cross-docking experiments in which each ligand of a protein ensemble was docked into each protein of the ensemble. Seventy-six percent of the docked structures had RMSDs below 2.0 A when the ligands were docked into foreign structures. We analyzed and validated GEMDOCK with respect to various search spaces and scoring functions, and found that if the scoring function was perfect, then the predicted accuracy was also essentially perfect. This study suggests that GEMDOCK is a useful tool for molecular recognition and may be used to systematically evaluate and thus improve scoring functions.

Algorithms↗

Assessing the relative contribution of molecular and morphological characters in simultaneous analysis trees.

We examined the contribution of morphological and molecular character information for 15 systematics studies in which these two kinds of data were used in combined or simultaneous analyses. Assessment of the disagreement between these data sources, as measured by the incongruence length difference, reveals substantial conflict for the studies surveyed. In addition, the partitioned Bremer support was used to measure the degree of support provided by each data partition when analyzed together. Despite the significant incongruence found for nearly half the studies, the PBS indices suggest both types of data contribute positively to the combined analyses and that, when standardized by the number of phylogenetically informative characters, morphology data generally provide equal or greater support than do the molecular data. This result, combined with the fact that morphological characters generally exhibit higher consistency, indicates that this source of character information continues to be useful in systematics studies despite the increasing volume of available molecular data.

Animals↗

Chronic-relapsing polyneuropathy in the course of cryoglobulinemia. Clinical aspects and plasmapheretic treatment.

During the last 3 years we have observed 7 cases (4.1%) of cryoglobulinemia-associated polyneuropathy out of 167 patients with demonstrated cryoglobulinemia. Nerve involvement in the course of cryoglobulinemia is usually symmetrical, affecting the distal portions of the limbs and has a chronic or chronic-relapsing evolution. In our experience, the combined treatment by plasmapheresis and glucocorticoids and/or cytostatic drugs has proved to be quite effective, particularly when instituted during the symptomatic exacerbations. Therefore, we suggest to perform a systematic investigation of the cryoglobulinemic phenomenon in every patient presenting with symptoms and/or signs of an apparently idiopathic polyneuropathy.

Adult↗

Anoperineal tuberculosis: diagnostic and management considerations in seven cases.

PURPOSE: Anoperineal tuberculosis is a rare extrapulmonary form of the disease that we must learn to recognize because it requires specific treatment. METHODS: Data from seven patients with anoperineal tuberculosis observed in a Parisian proctology unit between 1982 and 1999 were reviewed. RESULTS: All the patients were male (median age, 55 years); five were born in underdeveloped countries, and two were still living there. The average length of time between first manifestation of the disease and diagnosis was three years (range, 3 months to 9 years); all patients had undergone surgery previously. There were six recurring anal fistulas (complex in 5 cases) and one recurring abscess. In every case, the diagnosis had been suspected or confirmed by systematic histologic study of the surgically excised tissue. An association with pulmonary tuberculosis was found in each case. Treatment included two parts: conventional surgical treatment of anal sepsis and specific medical antituberculosis treatment. Evolution was favorable in all cases, with no recurrence of disease. Human immunodeficiency virus infection did not increase the incidence of anoperineal tuberculosis. CONCLUSION: Tuberculosis should be suspected in all recurrent fistulas. Histologic examination of the excised tissue and a lung x-ray should be performed to avoid delay in diagnosing an easily curable disease.

Adult↗

Food webs: experts consuming families of experts.

Food webs of habitats as diverse as lakes or desert valleys are known to exhibit common "food-web patterns", but the detailed mechanisms generating these structures have remained unclear. By employing a stochastic, dynamical model, we show that many aspects of the structure of predatory food webs can be understood as the traces of an evolutionary history where newly evolving species avoid direct competition with their relatives. The tendency to avoid sharing natural enemies (apparent competition) with related species is considerably weaker. Thus, "experts consuming families of experts" can be identified as the main underlying food-web pattern. We report the results of a systematic, quantitative model validation showing that the model is surprisingly accurate.

Animals↗

A molecular phylogeny of tortoises (Testudines: Testudinidae) based on mitochondrial and nuclear genes.

Although tortoises of the family Testudinidae represent a familiar and widely distributed group of turtles, their phylogenetic relationships have remained contentious. In this study, we included 32 testudinid species (all genera and subgenera, and all species of Geochelone, representing 65% of the total familial species diversity), and both mitochondrial (12S rRNA, 16S rRNA, and cytb) and nuclear (Cmos and Rag2) DNA data with a total of 3387 aligned characters. Using diverse phylogenetic methods (Maximum Parsimony, Maximum Likelihood, and Bayesian Analysis) congruent support is found for a well-resolved phylogeny. The most basal testudinid lineage includes a novel sister relationship between Asian Manouria and North American Gopherus. In addition, this phylogeny supports two other major testudinid clades: Indotestudo+Malacochersus+Testudo; and a diverse clade including Pyxis, Aldabrachelys, Homopus, Chersina, Psammobates, Kinixys, and Geochelone. However, we find Geochelone rampantly polyphyletic, with species distributed in at least four independent clades. Biogeographic analysis based on this phylogeny is consistent with an Asian origin for the family (as supported by the fossil record), but rejects the long-standing hypothesis of South American tortoises originating in North America. By contrast, and of special significance, our results support Africa as the ancestral continental area for all testudinids except Manouria and Gopherus. Based on our systematic findings, we also propose modifications concerning Testudinidae taxonomy.

Animals↗

Intergroup collaboration in ovarian cancer: a giant step forward.

The rather slow evolution of so-called "optimal chemotherapy" for ovarian cancer is the result of suboptimal randomised clinical trials, not having the statistical power to identify truly superior regimens, and of the lack of systematic comparisons of new agents with relevant control arms. There is little doubt that we need international collaboration to move the field forward in a timely and coherent manner. European and transatlantic collaboration represents the beginning of the process and point to the success that can await us if the drive to work together remains strong. A similar organisation as for breast cancer (Breast International Group, BIG) needs to be established for ovarian cancer.

Clinical Trials as Topic↗

Drug discovery--today and tomorrow: the role of medicinal chemistry.

Novel drugs presently introduced in the market are largely not discovered by rational design or by random screening but, rather, are products of evolution of existing leads (analogue research). It is suggested that this will change in the near future. Progress in a number of scientific disciplines will make it likely that drug design, but also systematic screening, will contribute more and more to novel drug discovery.

Chemistry, Pharmaceutical↗

Redox evolution of a degassing magma rising to the surface.

Volatiles carried by magmas, either dissolved or exsolved, have a fundamental effect on a variety of geological phenomena, such as magma dynamics and the composition of the Earth's atmosphere. In particular, the redox state of volcanic gases emanating at the Earth's surface is widely believed to mirror that of the magma source, and is thought to have exerted a first-order control on the secular evolution of atmospheric oxygen. Oxygen fugacity (f(O2) estimated from lava or related gas chemistry, however, may vary by as much as one log unit, and the reason for such differences remains obscure. Here we use a coupled chemical-physical model of conduit flow to show that the redox state evolution of an ascending magma, and thus of its coexisting gas phase, is strongly dependent on both the composition and the amount of gas in the reservoir. Magmas with no sulphur show a systematic f(O2) increase during ascent, by as much as 2 log units. Magmas with sulphur show also a change of redox state during ascent, but the direction of change depends on the initial f(O2) in the reservoir. Our calculations closely reproduce the H2S/SO2 ratios of volcanic gases observed at convergent settings, yet the difference between f(O2) in the reservoir and that at the exit of the volcanic conduit may be as much as 1.5 log units. Thus, the redox state of erupted magmas is not necessarily a good proxy of the redox state of the gases they emit. Our findings may require re-evaluation of models aimed at quantifying the role of magmatic volatiles in geological processes.

Journal Article↗

Transcriptional analyses of Barrett's metaplasia and normal upper GI mucosae.

Over the last two decades, the incidence of esophageal adenocarcinoma (EA) has increased dramatically in the US and Western Europe. It has been shown that EAs evolve from premalignant Barrett's esophagus (BE) tissue by a process of clonal expansion and evolution. However, the molecular phenotype of the premalignant metaplasia, and its relationship to those of the normal upper gastrointestinal (GI) mucosae, including gastric, duodenal, and squamous epithelium of the esophagus, has not been systematically characterized. Therefore, we used oligonucleotide-based microarrays to characterize gene expression profiles in each of these tissues. The similarity of BE to each of the normal tissues was compared using a series of computational approaches. Our analyses included esophageal squamous epithelium, which is present at the same anatomic site and exposed to similar conditions as Barrett's epithelium, duodenum that shares morphologic similarity to Barrett's epithelium, and adjacent gastric epithelium. There was a clear distinction among the expression profiles of gastric, duodenal, and squamous epithelium whereas the BE profiles showed considerable overlap with normal tissues. Furthermore, we identified clusters of genes that are specific to each of the tissues, to the Barrett's metaplastic epithelia, and a cluster of genes that was distinct between squamous and non-squamous epithelia.

Barrett Esophagus↗