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PubMed2004

Comparative analysis of complete genomes reveals gene loss, acquisition and acceleration of evolutionary rates in Metazoa, suggests a prevalence of evolution via gene acquisition and indicates that the evolutionary rates in animals tend to be conserved.

In this study we systematically examined the differences between the proteomes of Metazoa and other eukaryotes. Metazoans (Homo sapiens, Ceanorhabditis elegans and Drosophila melanogaster) were compared with a plant (Arabidopsis thaliana), fungi (Saccharomyces cerevisiae and Schizosaccaromyces pombe) and Encephalitozoan cuniculi. We identified 159 gene families that were probably lost in the Metazoan branch and 1263 orthologous families that were specific to Metazoa and were likely to have originated in their last common ancestor (LCA). We analyzed the evolutionary rates of pan-eukaryotic protein families and identified those with higher rates in animals. The acceleration was shown to occur in: (i) the LCA of Metazoa or (ii) independently in the Metazoan phyla. A high proportion of the accelerated Metazoan protein families was found to participate in translation and ribosome biogenesis, particularly mitochondrial. By functional analysis we show that no metabolic pathway in animals evolved faster than in other organisms. We conclude that evolution in the LCA of Metazoa was extensive and proceeded largely by gene duplication and/or invention rather than by modification of extant proteins. Finally, we show that the rate of evolution of a gene family in animals has a clear, but not absolute, tendency to be conserved.

Animals↗

PubMed2002

Molecular evolution of proteins involved in vertebrate phototransduction.

Vision is one of the most important senses for vertebrates. As a result, vertebrates have evolved a highly organized system of retinal photoreceptors. Light triggers an enzymatic cascade, called the phototransduction cascade, that leads to the hyperpolarization of photoreceptors. It is expected that a systematic comparison of phototransduction cascades of various vertebrates can provide insights into the diversity of vertebrate photoreceptors and into the evolution of vertebrate vision. However, only a few attempts have been made to compare each phototransduction protein participating in this cascade. Here, we determine phylogenetic trees of the vertebrate phototransduction proteins and compare them. It is demonstrated that vertebrate opsin sequences fall into five fundamental subfamilies. It is speculated that this is crucial for the diversity of the spectral sensitivity observed in vertebrate photoreceptors and provides the vertebrates with the molecular tools to discriminate the color of incident light. Other phototransduction proteins can be classified into only a few subfamilies. Cones generally share isoforms of phototransduction proteins that are different from those found in rods. The difference in sensitivity to light between rods and cones is likely due to the difference in the molecular properties of these isoforms. The phototransduction proteins seem to have co-evolved as a system. Switching the expression of these isoforms may characterize individual vertebrate photoreceptors.

Amino Acid Sequence↗

PubMed1991

Co-evolution of parasites and adaptive immune responses.

The interplay between evolving host populations and evolving parasite populations is dominated by two key genetically based elements, namely the virulence of parasites and the resistance of their hosts. Here, Graham Mitchell gives a personal overview of ideas on the coevolution of parasite-host relationships and the contributions to immunology that are likely to emerge from systematic studies on this relationship.

Adaptation, Biological↗

PubMed2002

Extensive genomic duplication during early chordate evolution.

Opinions on the hypothesis that ancient genome duplications contributed to the vertebrate genome range from strong skepticism to strong credence. Previous studies concentrated on small numbers of gene families or chromosomal regions that might not have been representative of the whole genome, or used subjective methods to identify paralogous genes and regions. Here we report a systematic and objective analysis of the draft human genome sequence to identify paralogous chromosomal regions (paralogons) formed during chordate evolution and to estimate the ages of duplicate genes. We found that the human genome contains many more paralogons than would be expected by chance. Molecular clock analysis of all protein families in humans that have orthologs in the fly and nematode indicated that a burst of gene duplication activity took place in the period 350 650 Myr ago and that many of the duplicate genes formed at this time are located within paralogons. Our results support the contention that many of the gene families in vertebrates were formed or expanded by large-scale DNA duplications in an early chordate. Considering the incompleteness of the sequence data and the antiquity of the event, the results are compatible with at least one round of polyploidy.

Animals↗

PubMed2003

Comparing the clinical evolution of cystic fibrosis screened neonatally to that of cystic fibrosis diagnosed from clinical symptoms: a 10-year retrospective study in a French region (Brittany).

Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a few regions of France. The Brittany region began in 1989, but not the neighboring region of Loire-Atlantique. The present study compares the clinical evolution of both affected populations 10 years after screening was started. Although the 77 screened and 36 nonscreened children were followed in different CF centers, they were included in similar care protocols. The clinical characteristics at diagnosis and their evolution over a 10-year period of all the children affected with CF and born between January 1, 1989 and December 31, 1998, excluding those with meconium ileus, were compared. There were no significant differences in sex ratio, gestational age, anthropometric data at birth, frequency of deltaF508 homozygotes, proportion of pancreatic-insufficient patients, and mean age between the two populations. Age at diagnosis was lower in the screened group (38 days vs. 472 days, P < 10(-7)), as was the delay in supplementation with pancreatic enzymes (1.7 months vs.15.9 months, P < 10(-7)). The proportion of children who were hospitalized at least once was higher among the nonscreened than the screened patients (86% vs. 49%, P < 10(-4)). Z-scores for weight and height were significantly better in the screened population, not only in the first years of life, but also at 5 years old for height and 8 years old for weight. The Shwachman and Brasfield scores were higher among the screened children during the whole period of follow-up. No significant differences in colonization by Pseudomonas aeruginosa nor in lung function were found. Given the homogeneity in the characteristics and the follow-up of both populations, the benefits in terms of nutrition and clinical well-being of neonatal screening appear to be clear, thus confirming the advantages of its general implementation.

Age of Onset↗

PubMed2006

Coevolutionary dynamics in large, but finite populations.

Coevolving and competing species or game-theoretic strategies exhibit rich and complex dynamics for which a general theoretical framework based on finite populations is still lacking. Recently, an explicit mean-field description in the form of a Fokker-Planck equation was derived for frequency-dependent selection with two strategies in finite populations based on microscopic processes [A. Traulsen, J. C. Claussen, and C. Hauert, Phys. Rev. Lett. 95, 238701 (2005)]. Here we generalize this approach in a twofold way: First, we extend the framework to an arbitrary number of strategies and second, we allow for mutations in the evolutionary process. The deterministic limit of infinite population size of the frequency-dependent Moran process yields the adjusted replicator-mutator equation, which describes the combined effect of selection and mutation. For finite populations, we provide an extension taking random drift into account. In the limit of neutral selection, i.e., whenever the process is determined by random drift and mutations, the stationary strategy distribution is derived. This distribution forms the background for the coevolutionary process. In particular, a critical mutation rate uc is obtained separating two scenarios: above uc the population predominantly consists of a mixture of strategies whereas below uc the population tends to be in homogeneous states. For one of the fundamental problems in evolutionary biology, the evolution of cooperation under Darwinian selection, we demonstrate that the analytical framework provides excellent approximations to individual based simulations even for rather small population sizes. This approach complements simulation results and provides a deeper, systematic understanding of coevolutionary dynamics.

Animals↗

PubMed1994

Quantification of tertiary structural conservation despite primary sequence drift in the globin fold.

The globin family of protein structures was the first for which it was recognized that tertiary structure can be highly conserved even when primary sequences have diverged to a virtually undetectable level of similarity. This principle of structural inertia in molecular evolution is now evident for many other protein families. We have performed a systematic comparison of the sequences and structures of 6 representative hemoglobin subunits as diverse in origin as plants, clams, and humans. Our analysis is based on a 97-residue helical core in common to all 6 structures. Amino acid sequence identities range from 12.4% to 42.3% in pairwise comparisons, and, despite these variations, the maximal RMS deviation in alpha-carbon positions is 3.02 A. Overall, sequence similarity and structural deviation are significantly anticorrelated, with a correlation coefficient of -0.71, but for a set of structures having under 20% pairwise identity, this anticorrelation falls to -0.38, which emphasizes the weak connection between a specific sequence and the tertiary fold. There is substantial variability in structure outside the helical core, and functional characteristics of these globins also differ appreciably. Nevertheless, despite variations in detail that the sequence dissimilarities and functional differences imply, the core structures of these globins remain remarkably preserved.

Amino Acid Sequence↗

PubMed2006

Central laboratory and point of care assessment of perioperative hemostasis.

PURPOSE: To review laboratory investigations required for the diagnosis of a constitutional or acquired defect of hemostasis before surgery, or during the perioperative period in context of rapid evolution and possible therapeutic adjustment. METHODS: A review of the literature. PRINCIPAL FINDINGS: Systematic preoperative screening is poorly efficient. It should be restricted to patients selected on clinical history and physical examination. Intra- and postoperative investigation is oriented by the clinical circumstances. In most instances, laboratory investigation is organized as hierarchical steps, the first one including a platelet count, a prothrombin time and activated partial thromboplastin time. According to the results of these assays and to the clinical circumstances, further tests specific of primary hemostasis, coagulation or fibrinolysis are performed. Point of care (POC) monitoring has been developed more recently for the investigation of a perioperative bleeding. Several tests examine platelet functions, others measure whole blood activated partial thromboplastin time or prothrombin time and some explore global hemostasis, allowing the detection of excessive fibrinolysis. Point of care testing provides a rapid and valuable answer but, if one accepts the monitoring of unfractionated heparin during extracorporeal circulation, most assays have not been properly validated. CONCLUSION: The investigation of hemostasis at the central laboratory and POC testing have distinct objectives. The utility of the former for the diagnosis and the adjustment of therapeutics have been well demonstrated. In contrast, the experience with POC testing is relatively recent, and its utility for patient management remains to be demonstrated in proper clinical trials.

Blood Coagulation Disorders↗

PubMed2003

Phylogeny of sheep and goat Theileria and Babesia parasites.

The phylogenetic relationship of Theileria and Babesia species infecting sheep and goats on the basis of their 18S RNA gene structure was addressed in the present study. For this purpose, the complete sequences of the small ribosomal RNA genes of a panel of sheep and goat piroplasm isolates, including T. lestoquardi, T. ovis, T. separata, B. ovis, B. motasi, B. crassa and several novel species, were sequenced and compared. The classification based on the established phylogenetic tree corresponded with traditional systematics and revealed that sheep/goat piroplasm species are of polyphyletic origin. The independent evolution of almost all sheep/goat piroplasms suggests that speciation may have occurred after transfer of the piroplasm-transmitting tick from a primal wild ruminant host to domestic sheep and goats. In accordance with recent reports, our study confirms the existence of at least two additional sheep/goat piroplasm species, designated Theileria sp. 1 (China) and Theileria sp. 2 (China). The recently reported pathogenic sheep/goat Theileria sp. 1 (China) seems to be identical with a Theileria sp. isolated from Japanese serow. Furthermore, our results suggest that T. ovis represents a single species.

Animals↗

PubMed1987

Phylogenetic receptor research: implications in studying psychiatric and neurological disease.

Phylogenetic studies will help to evaluate the structure and function of receptors. We were able to show that the regional heterogeneity of the central benzodiazepine receptor previously described in mammals also applies to avians. In addition, a systematic species comparison of the subunit patterns revealed a certain phylogenetic relationship suggesting evolution by gene duplication and subsequent divergence. In analogy to isozyme systems, these results possibly indicate that the GABA/benzodiazepine receptor is an isoreceptor complex. The implications for neuropsychiatric genetics are discussed.

Animals↗

PubMed2004

Fermi surface of NaxCoO2.

Doping evolution of the Fermi surface topology of Na(x)CoO(2) is studied systematically. Both local density approximation (LDA) and local spin density approximation (LSDA) predict a large Fermi surface as well as small hole pockets for doping levels x approximately 0.5. In contrast, the hole pockets are completely absent for all doping levels within LSDA+U. More importantly, we find no violation of Luttinger's rule in this system. The measured Fermi surface of Na(0.7)CoO(2) can be explained by its half-metallic behavior and agrees with our LSDA+U calculations.

Journal Article↗

PubMed1992

Women healers of the middle ages: selected aspects of their history.

The stellar role of women as healers during the Middle Ages has received some attention from medical historians but remains little known or appreciated. In the three centuries preceding the Renaissance, this role was heightened by two roughly parallel developments. The first was the evolution of European universities and their professional schools that, for the most part, systematically excluded women as students, thereby creating a legal male monopoly of the practice of medicine. Ineligible as healers, women waged a lengthy battle to maintain their right to care for the sick and injured. The 1322 case of Jacqueline Felicie, one of many healers charged with illegally practicing medicine, raises serious questions about the motives of male physicians in discrediting these women as incompetent and dangerous. The second development was the campaign--promoted by the church and supported by both clerical and civil authorities--to brand women healers as witches. Perhaps the church perceived these women, with their special, often esoteric, healing skills, as a threat to its supremacy in the lives of its parishioners. The result was the brutal persecution of unknown numbers of mostly peasant women.

Clinical Medicine↗

PubMed2026

Molecular mechanisms underlying drug resistance in protozoan parasites: emerging mechanisms and therapeutic perspectives.

Protozoan parasitic infections, including malaria, leishmaniasis, and human African trypanosomiasis, remain major global public health challenges. In the absence of highly effective vaccines, disease control relies primarily on chemotherapy; however, the emergence and spread of drug-resistant parasite populations increasingly threaten treatment efficacy. This review synthesizes current evidence on the molecular mechanisms underlying drug resistance in Plasmodium, Leishmania, and Trypanosoma species through a systematic analysis of literature. The review identifies four interconnected mechanisms that drive the evolution of drug resistance. First, altered drug transport enables parasites to regulate intracellular drug concentrations through mutations, loss, or amplification of membrane transporters, including PfCRT in Plasmodium and AQP2 in Trypanosoma brucei. Second, target modification and genomic plasticity promote resistance through point mutations in drug targets, such as dhfr and dhps in Plasmodium, while kinetoplastids, particularly Leishmania, exploit extensive genomic plasticity, including aneuploidy, gene amplification, and translational reprogramming, to facilitate rapid adaptation under drug pressure. Third, metabolic reprogramming enhances parasite survival by increasing intracellular thiol production, strengthening antioxidant defense systems, and reshaping central carbon and lipid metabolism to mitigate drug-induced stress. Finally, stress response and persistence mechanisms enable subpopulations of parasites to enter dormant, persister-like states characterized by reduced metabolic activity and slowed proliferation, thereby evading both host immune responses and chemotherapeutic agents. Collectively, these findings demonstrate that drug resistance is a dynamic, multifactorial evolutionary process rather than a single molecular event. Addressing this growing challenge requires integrating genomic surveillance, molecular diagnostics, mathematical modeling of resistance transmission, and mechanistic insights into parasite persistence into future drug discovery and disease control strategies. Such an integrated approach is essential for improving the durability of antiprotozoal therapies and advancing global efforts to control neglected protozoan diseases.

antiprotozoal therapy↗

PubMed2000

The history of liver disease at The Mount Sinai Hospital.

Diseases of the liver and biliary tract interested the physicians of The Mount Sinai Hospital from the time the hospital started until the present. Indeed, the institution has become a well-recognized center for the study of the liver and its diseases. During the first 75 years of the hospital, there were many admissions for hepatobiliary diseases, resulting in many case reports. The evolution of the hospital into a teaching hospital brought with it a more systematic method of studying diseases, not only in Pathology under Paul Klemperer, but in clinical chemistry and microbiology as well. Liver biopsy was also attempted. With the arrival of Hans Popper in 1957, the emphasis shifted to coordinated studies of structure and function under normal circumstances and in diseases as they progressed. Soon, Liver Diseases (Hepatology) were split from Gastroenterology, with Fenton Schaffner as the first chief. Over the next 30 years, more than 1000 papers, chapters and books were published. The main areas of research were fibrosis, cholestasis (especially morphology and bile salt metabolism), toxic liver injury, metabolic transformations and carcinogenesis. Primary biliary cirrhosis and viral hepatitis were and continue to be special interests. Fellows from all over the world were trained and many moved on to leadership positions. Although he was active in the development of the liver transplant program, Popper did not live to see its start. A new generation of hepatologists maintains the interest and position of The Mount Sinai Hospital in this important field of medicine.

History, 19th Century↗

PubMed1990

Artiodactylan phylogeny: an immunogenetic study based on comparative determinant analysis.

The phylogenetic relationships of major artiodactylan taxa were investigated by means of comparative determinant analysis (CDA). Monospecific antisera against taurine cattle albumin, transferrin, C3 and IgM were used to derive determinant formulas of their homologues in 21 species (plus 12 other mammals for outgroup comparison). Fifteen accepted mutations could be demonstrated in Artiodactyla, permitting recognition of nine immunologically defined species groups. Results with phylogenetically relevant implications include the clear immunogenetic separation of the vicugna from true ruminants, a complex pattern of accepted mutations rendering a genealogical analysis of the principal pecoran radiation difficult, one synapomorphic mutation combining the goitred gazelle with bovines but excluding Caprinae, and the immunological recognition of the three grades of wild cattle evolution. This study demonstrates the suitability of CDA as a tool of phylogenetic systematics above the level of genera.

Albumins↗

PubMed1990

[Thyroid cancer and familial rectocolonic polyposis].

Thyroid carcinoma and familial intestinal polyposis are not accidentally associated. A new case is described which, along with the other 32 cases already published, reveals an incidence of thyroid carcinoma 100 times higher in patients with polyposis than in the general population, and 160 times higher in female patients under 35 years of age. Several features of these thyroid carcinomas can be pointed out: greatest incidence in women, occurrence at a young age, existence of a papillary tumor appearing independently from the evolution of the polyposis, and probably familial disease. It is therefore necessary to systematically examine the thyroid body in all subjects with familial intestinal polyposis.

Adenomatous Polyposis Coli↗

PubMed1990

[Acute respiratory distress syndrome in the initial phase of myocardial infarction in adults].

Four patients developed an acute respiratory distress syndrome characterised by clinical and radiological signs of pulmonary oedema, a protein-rich oedema, severe hypoxemia refractory to oxygen therapy, contrasting with normal left ventricular filling pressures and indicating increased permeability of the alveolo-capillary membrane, 24 to 72 hours after the onset of acute myocardial infarction. After having excluded the usual causes of the acute respiratory distress syndrome, the authors suggest that acute myocardial infarction, especially when extensive, may cause a lesion of the alveolo-capillary membrane by an unknown mechanism. Treatment consisted in mechanical ventilation with positive expiratory pressures in 3 cases and with continuous positive pressure during spontaneous respiration in the third patient and in relay with controlled ventilation in the other two. These techniques of ventilation improved the hypoxemia and led to complete cure in all cases without evolution to pulmonary fibrosis. In addition to mechanical ventilation, all patients were given systematic antibiotic therapy because of the possibility of an infectious etiology while waiting for the results of microbiological and serological testing and because of the high risk of superinfection which plays an essential part in the outcome of the condition. The immediate response to treatment was favourable in all cases. One patient died suddenly of cardiogenic shock two weeks after this episode. The other patients are still alive 39, 38 and 20 months after infarction. The importance of the diagnosis of the acute respiratory distress syndrome in the acute phase of myocardial infarction resides in its therapeutic implications which are quite different to those of cardiogenic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1984

[Cardiac transplantation: noninvasive detection of rejection by echocardiography].

The main objective of follow-up of cardiac transplant patients is early recognition of acute rejection of the allogenic myocardium. Two patients followed up by the usual protocol also underwent routine M-mode and 2D echocardiography. The data was digitalized and memorized to allow systematic study of the pericardial and cardiac structures, and a comparison of their evolution. Acute rejection was associated with an increase in the acoustic density of the myocardium, especially of the interventricular septum, and an increase in myocardial mass as calculated from M-mode data; an increase of 5 p. 100 of this parameter with respect to an average reference value was judged to be significant. Comparisons were made with electrocardiographic data, especially with an index of voltage. The variability of this index which may be unrelated to rejection was apparent; in addition, there was an interval of about 5 days between the echocardiographic changes and the recording of significant reductions of the electrocardiographic index. Previously reported histological changes explain the precocity and reliability of the echocardiographic results obtained by a non-invasive and reproducible method.

Adult↗