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PubMed1997

Reciprocal changes in circulating interleukin-6 and its soluble receptor during evolving sepsis in leukocytopenic patients.

Plasma concentrations of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) were serially determined in 32 patients with acute myeloid leukemia who developed severe sepsis (n = 19) or septic shock (n = 13) during chemotherapy-induced leukocytopenia (< or = 1 x 10(9)/L). Starting within 2 h of fever onset, IL-6 levels rose significantly over baseline in both groups to markedly higher levels in patients with evolving septic shock (medians: 372 vs. 3671 pg/mL; P < .001). Simultaneously, sIL-6R significantly decreased to lower levels in shock patients than in septic patients without hypotension (53 vs. 93 ng/mL; P = .02). This pattern was maintained throughout the observation period of up to 6 days. In patients with fatal sepsis, peak IL-6 levels were significantly higher than in survivors (P < .001), whereas minimum sIL-6R levels were markedly lower (P = .003). The reciprocal changes in circulating IL-6 and sIL-6R suggest a role for sIL-6R in modulating the effects of IL-6 during evolving sepsis in leukocytopenic patients.

Acute Disease↗
PubMed1997

Evolving isolated hand palsy: a parietal lobe syndrome associated with carotid artery disease.

Six patients with cerebral ischaemia who presented evolving isolated hand palsy were studied, five prospectively and one retrospectively. The motor deficit involved only the hand and the wrist in some cases. In almost all cases the motor deficit was pseudo-ulnar. None of them had a Babinski sign, all had mild sensory symptoms or signs in the affected hand. CT and MRI disclosed recent infarctions contralateral to the affected hand, in the white matter of the angular gyrus, in a vascular borderzone. Five had a tight stenosis of the internal carotid artery. The pyramidal tract was anatomically spared in three cases, even considering its parietal origin. Consistent with previous data, our study suggests that the parietal lobe is involved in the control of the motor function of the hand. We propose the existence of a new entity, characterized by an evolving non-pyramidal motor deficit in the hand following infarction of the angular gyrus of the inferior parietal lobe.

Aged↗
PubMed1990

Pathophysiological role of changing atrial size and pressure in modulation of atrial natriuretic factor during evolving experimental heart failure.

STUDY OBJECTIVE: The aim was to study the interactions between pulmonary capillary wedge pressure (an estimate of left atrial pressure), left atrial dimension, and atrial natriuretic factor during evolving heart failure. DESIGN: Sequential simultaneous measurements of haemodynamic variables, left atrial dimension, and plasma atrial natriuretic factor concentrations were obtained during evolving experimental pacing induced heart failure. EXPERIMENTAL MATERIAL: Eight male mongrel dogs were paced (250 beats.min-1) to severe heart failure over 4.9(SD 1.8) weeks. MEASUREMENTS AND RESULTS: The development of heart failure was characterised by a progressive increase in pulmonary capillary wedge pressure and left atrial cross sectional area, from 5.6(1.3) mm Hg and 7.9(1.2) cm2 respectively at control, to 25.3(4.9) mm Hg and 14.2(2.5) cm2 respectively (both p less than 0.01) at severe heart failure. In contrast to the progressive increase in pulmonary capillary wedge pressure and left atrial area, plasma atrial natriuretic factor concentration increased from 98(51) ng.litre-1 at control to a peak of 422(110) ng.litre-1 (p less than 0.01) at 1 week, then plateaued and reached 354(108) ng.litre-1 at severe heart failure (p less than 0.05 v control). Plasma atrial natriuretic factor correlated with pulmonary capillary wedge pressure and left atrial area at 1 week (r = 0.73, r = 0.71 respectively, both p less than 0.01), but not at the time of severe heart failure. CONCLUSION: The divergent time course of the changes in plasma atrial natriuretic factor concentration, pulmonary capillary wedge pressure, and left atrial dimension suggests that in this model, the release of atrial natriuretic factor becomes attenuated as severe heart failure develops.

Animals↗
PubMed1985

Physiological characterization of adaptive clones in evolving populations of the yeast, Saccharomyces cerevisiae.

Populations of a diploid strain of S. cerevisiae were grown in glucose-limited continuous culture for more than 260 generations. A series of seven sequential adaptive changes were identified by monitoring the frequency of cycloheximide resistance in these populations. Samples were taken from the continuous cultures following each adaptive shift and characterized physiologically to determine (1) the range of phenotypes that can be selected in a precisely defined constant environment and (2) the order and predictability of the occurrence of the adaptive mutations in evolving populations. The clones were characterized with respect to the growth parameters, maximum growth rate, saturation coefficient and yield, as well as for changes in cell size and geometry and rate of glucose uptake. The maximum growth rates of the seven adaptive clones were very similar, but in contrast the saturation coefficients differed substantially. Surprisingly, not all clones showed reductions in the saturation coefficients, in comparison to the immediately preceding clones, as would be predicted from classical continuous culture kinetics. In addition, yield estimates first increased and then decreased for later isolated adaptive clones. In general, the results suggest epistatic interactions between the adaptive clones, consistent with earlier published results. The rate of glucose uptake, as measured by 14C-xylose uptake, increased dramatically after the selection and fixation of seven adaptive clones. Progressive decreases in cell volume and changes in cell geometry, resulting in increased surface area to volume ratios, were also observed in the adaptive clones, but these changes were not always seen in other haploid and diploid yeast populations evolving under the same conditions. Such changes may be easily explainable in terms of the characteristics of the glucose-limited environment. The significance of the results to the evolution of microorganisms under nutrient-limiting conditions is discussed.

Biological Transport↗
PubMed1992

Comparing evolvability and variability of quantitative traits.

There are two distinct reasons for making comparisons of genetic variation for quantitative characters. The first is to compare evolvabilities, or ability to respond to selection, and the second is to make inferences about the forces that maintain genetic variability. Measures of variation that are standardized by the trait mean, such as the additive genetic coefficient of variation, are appropriate for both purposes. Variation has usually been compared as narrow sense heritabilities, but this is almost always an inappropriate comparative measure of evolvability and variability. Coefficients of variation were calculated from 842 estimates of trait means, variances and heritabilities in the literature. Traits closely related to fitness have higher additive genetic and nongenetic variability by the coefficient of variation criterion than characters under weak selection. This is the reverse of the accepted conclusion based on comparisons of heritability. The low heritability of fitness components is best explained by their high residual variation. The high additive genetic and residual variability of fitness traits might be explained by the great number of genetic and environmental events they are affected by, or by a lack of stabilizing selection to reduce their phenotypic variance. Over one-third of the quantitative genetics papers reviewed did not report trait means or variances. Researchers should always report these statistics, so that measures of variation appropriate to a variety of situations may be calculated.

Animals↗
PubMed1995

How often do duplicated genes evolve new functions?

A recently duplicated gene can either fix a null allele (becoming a pseudogene) or fix an (advantageous) allele giving a slightly different function, starting it on the road to evolving a new function. Here we examine the relative probabilities of these two events under a simple model. Null alleles are assumed to be neutral; linkage effects are ignored, as are unequal crossing over and gene conversion. These assumptions likely make our results underestimates for the probability that an advantageous allele is fixed first. When new advantageous mutations are additive with selection coefficient s and the ratio of advantageous to null mutations is rho, the probability an advantageous allele is fixed first is ([1 - e-s]/[rho S] + 1)-1, where S = 4Nes with Ne the effective population size. The probability that a duplicate locus becomes a pseudogene, as opposed to evolving a new gene function, is high unless rhoS >> 1. However, even if advantageous mutations are very rare relative to null mutations, for sufficiently large populations rhoS >> 1 and new gene function, rather than pseudogene formation, is the expected fate of most duplicated genes.

Biological Evolution↗
PubMed1999

Large number of replacement polymorphisms in rapidly evolving genes of Drosophila. Implications for genome-wide surveys of DNA polymorphism.

We present a survey of nucleotide polymorphism of three novel, rapidly evolving genes in populations of Drosophila melanogaster and D. simulans. Levels of silent polymorphism are comparable to other loci, but the number of replacement polymorphisms is higher than that in most other genes surveyed in D. melanogaster and D. simulans. Tests of neutrality fail to reject neutral evolution with one exception. This concerns a gene located in a region of high recombination rate in D. simulans and in a region of low recombination rate in D. melanogaster, due to an inversion. In the latter case it shows a very low number of polymorphisms, presumably due to selective sweeps in the region. Patterns of nucleotide polymorphism suggest that most substitutions are neutral or nearly neutral and that weak (positive and purifying) selection plays a significant role in the evolution of these genes. At all three loci, purifying selection of slightly deleterious replacement mutations appears to be more efficient in D. simulans than in D. melanogaster, presumably due to different effective population sizes. Our analysis suggests that current knowledge about genome-wide patterns of nucleotide polymorphism is far from complete with respect to the types and range of nucleotide substitutions and that further analysis of differences between local populations will be required to understand the forces more completely. We note that rapidly diverging and nearly neutrally evolving genes cannot be expected only in the genome of Drosophila, but are likely to occur in large numbers also in other organisms and that their function and evolution are little understood so far.

Animals↗
PubMed2003

An analysis of why highly similar enzymes evolve differently.

The TEM-1 and SHV-1 beta-lactamases are important contributors to resistance to beta-lactam antibiotics in gram-negative bacteria. These enzymes share 68% amino acid sequence identity and their atomic structures are nearly superimposable. Extended-spectrum cephalosporins were introduced to avoid the action of these beta-lactamases. The widespread use of antibiotics has led to the evolution of variant TEM and SHV enzymes that can hydrolyze extended-spectrum antibiotics. Despite being highly similar in structure, the TEM and SHV enzymes have evolved differently in response to the selective pressure of antibiotic therapy. Examples of this are at residues Arg164 and Asp179. Among TEM variants, substitutions are found only at position 164, while among SHV variants, substitutions are found only at position 179. To explain this observation, the effects of substitutions at position 164 in both TEM-1 and SHV-1 on antibiotic resistance and on enzyme catalytic efficiency were examined. Competition experiments were performed between mutants to understand why certain substitutions preferentially evolve in response to the selective pressure of antibiotic therapy. The data presented here indicate that substitutions at position Asp179 in SHV-1 and Arg164 in TEM-1 are more beneficial to bacteria because they provide increased fitness relative to either wild type or other mutants.

Ceftazidime↗
PubMed2025

Redundant and Singular Regulatory Elements Underlie the Rapidly Evolving Pigmentation of Drosophila.

A major hurdle in understanding the molecular changes responsible for metazoan diversity is the characterization of cis-regulatory elements (CREs) for gene regulatory networks (GRNs). CRE changes are suspected to be commonplace in trait evolution, since such changes circumvent the deleterious effects of pleiotropy. A growing list of genes, though, is known to be regulated by redundant CREs. Such redundant CRE architectures complicate the characterization of GRN evolution, as they compound the effort to characterize each locus, and raise the questions of how and whether genes with redundant architectures evolve expression. Here, we used the evolution of sexually dimorphic abdomen pigmentation of Drosophila (D.) melanogaster as a model to study the function and evolution of CREs. Numerous sequences were evaluated that were previously predicted as potential abdomen CREs. Most of these predictions were validated, including two, four, and ten that, respectively, reside in the homothorax, grainy head, and Eip74EF transcription factor loci. The homothorax CREs were found to be partially redundant for this gene's pigmentation function, and pupal-stage Homothorax expression and the CRE activities were conserved among Drosophila species with the derived dimorphic and ancestral monomorphic phenotypes. Similarly, the Eip74EF CREs were conserved in the monomorphic D. willistoni. Thus, this gene's extensive CRE spatiotemporal redundancy has been conserved for over 30 million years, predating the dimorphic trait. Pigmentation evolution has been connected elsewhere to changes in nonredundant CREs. When these traits evolve, GRN changes may be biased towards the genes with singular nonredundant CREs, while the expression of redundantly regulated genes remains conserved.

Animals↗
PubMed2003

Rapidly evolving genes in human. I. The glycophorins and their possible role in evading malaria parasites.

In an attempt to identify all fast-evolving genes between human and other primates, we found three glycophorins, GPA, GPB, and GPE, to have the highest rate of nonsynonymous substitutions among the 280 genes surveyed. The Ka/Ks ratios are generally greater than 3 for GPA, GPB, and GPE in human, chimpanzee, and gorilla, indicating positive selection. The uniformly high substitution rate across loci can be explained by the frequent sequence exchanges among genes. GPA is the receptor for the binding ligand EBA-175 of the malaria parasite, Plasmodium falciparum. The levels of nonsynonymous divergence and polymorphism of EBA-175 are also the highest in the genome of P. falciparum. We hypothesize that GPA has been evolving rapidly to evade malaria parasites. Both the high rate of nonsynonymous substitutions and the frequent interlocus conversions may be means of evasion. The support for the evasion hypothesis is still indirect, but, unlike other hypotheses, it can be tested specifically and systematically.

Alleles↗
PubMed2003

Sex-linked mammalian sperm proteins evolve faster than autosomal ones.

X-linked genes can evolve slower or faster depending on whether most recessive, or at least partially recessive alleles are deleterious or beneficial due to their hemizygous expression in males. Molecular studies of X chromosome divergence have provided conflicting evidence for both a higher and lower rate of nucleotide substitution at both synonymous and nonsynonymous sites, depending on the nucleotide sites sampled. Using human and mouse orthologous genes, we tested the hypothesis that genes encoding male-specific sperm proteins are evolving faster on the X chromosome compared with autosomes. X-linked sperm proteins have an average nonsynonymous mutation rate almost twice as high as sperm genes found on autosomes, unlike other tissue-specific genes, where no significant difference in the nonsynonymous mutation rate between the X chromosome and autosomes was found. However, no difference was found in the average synonymous mutation rate of X-linked versus autosomal sperm proteins, which along with corresponding higher values of Ka/Ks in X-linked sperm proteins suggest that differences in selective forces and not mutation rates are the underlying cause of higher X-linked mammalian sperm protein divergence.

Animals↗
PubMed2003

Mammalian housekeeping genes evolve more slowly than tissue-specific genes.

Do housekeeping genes, which are turned on most of the time in almost every tissue, evolve more slowly than genes that are turned on only at specific developmental times or tissues? Recent large-scale gene expression studies enable us to have a better definition of housekeeping genes and to address the above question in detail. In this study, we examined 1581 human-mouse orthologous gene pairs for their patterns of sequence evolution, contrasting housekeeping genes with tissue-specific genes. Our results show that, in comparison to tissue-specific genes, housekeeping genes on average evolve more slowly and are under stronger selective constraints as reflected by significantly smaller values of Ka/Ks. Besides stronger purifying selection, we explored several other factors that can possibly slow down nonsynonymous rates in housekeeping genes. Although mutational bias might slightly slow the nonsynonymous rates in housekeeping genes, it is unlikely to be the major cause of the rate difference between the two types of genes. The codon usage pattern of housekeeping genes does not seem to differ from that of tissue-specific genes. Moreover, contrary to the old textbook concept, we found that approximately 74% of the housekeeping genes in our study belong to multigene families, not significantly different from that of the tissue-specific genes ( approximately 70%). Therefore, the stronger selective constraints on housekeeping genes are not due to a lower degree of genetic redundancy.

Animals↗
PubMed2004

Selective expansion of the newly evolved genomic variants of retrotransposon 1731 in the Drosophila genomes.

The structural variants of the regulatory and coding regions of the LTR-retrotransposon 1731 are described. Two classes of genomic copies of retrotransposon 1731, with and without frameshifting strategy to express Gag and Pol proteins, were earlier revealed in the D. melanogaster genome. Copies without frameshifting are shown to be evolved from an ancient variant with frameshifting and are widespread in the genomes of the melanogaster complex species. Position of a rare codon responsible for ribosome pausing and efficient frameshifting is identified. Two structural variants of 1731 LTRs were detected in the melanogaster complex species: the predominant structural variant A1A2 of 1731 LTR in the D. melanogaster, D. simulans, and D. sechellia genomes contains duplicated and diverged copies of 28 bp in the U3 region, whereas A1 variant lacking this duplication is expanded in the D. mauritiana genome. Selective expansion of the A1A2 variant was detected in the independently established D. melanogaster cell cultures. A1A2 variant is expressed in embryos, cell culture, and testes, whereas A1 is expressed only in testes of D. melanogaster. Relief of expression of the A1A2 but not A1 variant in the ovaries as a result of mutation in the RNA interference (RNAi) spn-E gene is shown. Thus, expansion of the recently evolved genomic variants of the LTR retrotransposon 1731 possessing a new translation strategy, duplication in the U3 region, and extended profile of expression is revealed.

Animals↗
PubMed1995

Thrombolytic therapy for evolving myocardial infarction needs an approach that integrates benefit and risk.

Thrombolytic therapy is a major step forward in the treatment of acute myocardial infarction and results in substantial reduction of mortality. However, in individual patients the benefits and bleeding risk are difficult to estimate, especially when benefit seems small or outweighed by the risk of intracranial bleeding. For this and other reasons less than half the patients with evolving myocardial infarction are treated with thrombolytic therapy. We propose to approach the decision 'to treat or not to treat' in a systematic way, integrating estimated benefit and intracranial bleeding risk in individual patients. According to a decision-model developed with currently available medical knowledge, thrombolytic therapy appears beneficial in the majority of patients with evolving myocardial infarction provided that ST segment elevation is present and treatment can be started within 12 h of onset of symptoms. Thrombolytic therapy is warranted in the absence of risk factors for intracranial haemorrhage, even if the risk of cardiac death in the first year without thrombolytic therapy is as low as 2.3% (patients with small inferior wall infarctions). For patients with increased intracranial bleeding risk, the cardiac baseline risk without thrombolytic therapy and treatment delay become important variables to take into account when selecting thrombolytic therapy. Precise thresholds for these variables are presented.

Cerebral Hemorrhage↗
PubMed2002

Experimental phylogeny of neutrally evolving DNA sequences generated by a bifurcate series of nested polymerase chain reactions.

A known phylogeny was generated using a four-step serial bifurcate PCR method. The ancestor sequence (SSU rDNA) evolved in vitro for 280 nested PCR cycles, and the resulting 15 ancestor and 16 terminal sequences (2,238 bp each) were determined. Parsimony, distance, and maximum likelihood analysis of the terminal sequences reconstructed the topology of the real phylogeny and branch lengths accurately. Divergence dates and ancestor sequences were estimated with very small error, particularly at the base of the phylogeny, mostly due to insertion and deletion changes. The substitution patterns along the known phylogeny are not described by reversible models, and accordingly, the probability substitution matrix, based on the observed substitutions from ancestor to terminal nodes along the known phylogeny, was calculated. This approach is an extension of previous studies using bacteriophage serial propagation, because here mutations were allowed to occur neutrally rather than by addition of a mutagenic agent, which produced biased mutational changes. These results provide for the first time biochemical experimental support for phylogenies, divergence date estimates, and an irreversible substitution model based on neutrally evolving DNA sequences. The substitution preferences observed here (A to G and T to C) are consistent with the high G+C content of the Thermus aquaticus genome. This suggests, at least in part, that the method here described, which explores the high Taq DNA polymerase error rate, simulates the evolution of a DNA segment in a thermophilic organism. These organisms include the bacterial rod T. aquaticus and several Archaea, and thus, the method and data set described here may well contribute new insights about the genome evolution of these organisms.

Animals↗
PubMed2000

Evidence from beta-tubulin phylogeny that microsporidia evolved from within the fungi.

Microsporidia are obligate intracellular parasites that were thought to be an ancient eukaryotic lineage based on molecular phylogenies using ribosomal RNA and translation elongation factors. However, this ancient origin of microsporidia has been contested recently, as several other molecular phylogenies suggest that microsporidia are closely related to fungi. Most of the protein trees that place microsporidia with fungi are not well sampled, however, and it is impossible to resolve whether microsporidia evolved from a fungus or from a protistan relative of fungi. We have sequenced beta-tubulins from 3 microsporidia, 4 chytrid fungi, and 12 zygomycete fungi, expanding the representation of beta-tubulin to include all four fungal divisions and a wide diversity of microsporidia. In phylogenetic trees including these new sequences, the overall topology of the fungal beta-tubulins generally matched the expected relationships among the four fungal divisions, although the zygomycetes were polyphyletic in some analyses. The microsporidia consistently fell within this fungal diversification, and not as a sister group to fungi. Overall, beta-tubulin phylogeny suggests that microsporidia evolved from a fungus sometime after the divergence of chytrids. We also found that chytrid alpha- and beta-tubulins are much less divergent than are tubulins from other fungi or microsporidia. In trees in which the only fungal representatives were the chytrids, microsporidia still branched with fungi (i.e., with chytrids), suggesting that the affiliation between microsporidian and fungal tubulins is not an artifact of long-branch attraction.

Animals↗
PubMed2001

Isolation and characterization of oxygen-evolving thylakoid membranes and photosystem II particles from a glaucocystophyte, Cyanophora paradoxa.

Conditions for preparing oxygen-evolving thylakoid membranes and PSII complexes, and those for observing the PSII activity were investigated in a glaucocystophyte, Cyanophora paradoxa. The active thylakoid membranes were isolated either with a medium containing glycerol or with that containing high concentrations of sucrose, phosphate, and citrate. Active PSII particles were solubilized by octyl-beta-D-glucoside from thylakoid membranes and were separated by sucrose density gradient centrifugation. The thylakoid membranes and PSII particles showed an oxygen-evolving activity only in high-ionic-strength media. The extrinsic 33 kDa protein (PsbO) and the cytochrome c(550) (PsbV) were found to be present in the PSII particles as in cyanobacteria or red algae, but no 12 kDa protein (PsbU) was detected. The PsbO protein was classified as a land-plant type by its N-terminal amino acid sequence.

Absorptiometry, Photon↗
PubMed2003

Binding and functional properties of the extrinsic proteins in oxygen-evolving photosystem II particle from a green alga, Chlamydomonas reinhardtii having his-tagged CP47.

Oxygen-evolving photosystem II (PSII) particles were purified from Chlamydomonas reinhardtii having His-tag extension at the C terminus of the CP47 protein, by a single-step Ni(2+)-affinity column chromatography after solubilization of thylakoid membranes with sucrose monolaurate. The PSII particles consisted of, in addition to intrinsic proteins, three extrinsic proteins of 33, 23 and 17 kDa. The preparation showed a high oxygen-evolving activity of 2,300-2,500 micro mol O(2) (mg Chl)(-1) h(-1) in the presence of Ca(2+) using ferricyanide as the electron acceptor, while its activity was 680-720 micro mol O(2) (mg Chl)(-1) h(-1) in the absence of Ca(2+) and Cl(-) ions. The activity was 710-820 micro mol O(2) (mg Chl)(-1) h(-1) independent of the presence or absence of Ca(2+) and Cl(-) when 2,6-dichloro-p-benzoquinone was used as the acceptor. These activities were scarcely inhibited by DCMU. The kinetics of flash-induced fluorescence decay revealed that the electron transfer from Q(A)(-) to Q(B) was significantly inhibited, and the electron transfer from Q(A)(-) to ferricyanide was largely stimulated in the presence of Ca(2+). These results indicate that the acceptor side, Q(B) site, was altered in the PSII particles but its donor side remained intact. Release-reconstitution experiments revealed that the extrinsic 23 and 17 kDa proteins were released only partially by NaCl-wash, while most of the three extrinsic proteins were removed when treated with urea/NaCl, alkaline Tris or CaCl(2). The 23 and 17 kDa proteins directly bound to PSII independent of the other extrinsic proteins, and the 33 kDa protein functionally re-bound to CaCl(2)-treated PSII which had been reconstituted with the 23 and 17 kDa proteins. These binding properties were largely different from those of the extrinsic proteins in higher plant PSII, and suggest that each of the three extrinsic proteins has their own binding sites independent of the others in the green algal PSII.

Algal Proteins↗