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At least 649 records · Page 36Linked to original sources
PubMed1997

Functional analysis of the evolutionary conserved arginine 182 residue in human glutathione S-transferase P1-1.

The mutational replacement of Arg182 with threonine markedly decreased the specific activities for GSH-conjugation reaction. The Kcat of R182T for GSH-[1-chloro-2,4-dinitrobenzene] conjugation reaction was about 100-fold smaller than that of the wild type. On the other hand, the affinity for GSH of R182T was not significantly affected. The pKa of the thiol group of GSH bound in R182T was approximately 0.9 pK units higher than those in the wild type, but the Kcat/Km1-chloro-2,4-dinitrobenzene values at high pH were not so much lower than those of the wild type. The thermostability of R182T was significantly lower than that of the wild type. Therefore, Arg182 seems to be important for the construction of the active enzyme structure.

Amino Acid Sequence↗
PubMedDate not supplied

Efficient algorithms for protein sequence design and the analysis of certain evolutionary fitness landscapes.

Protein sequence design is a natural inverse problem to protein structure prediction: given a target structure in three dimensions, we wish to design an amino acid sequence that is likely fold to it. A model of Sun, Brem, Chan, and Dill casts this problem as an optimization on a space of sequences of hydrophobic (H) and polar (P) monomers; the goal is to find a sequence that achieves a dense hydrophobic core with few solvent-exposed hydrophobic residues. Sun et al. developed a heuristic method to search the space of sequences, without a guarantee of optimality or near-optimality; Hart subsequently raised the computational tractability of constructing an optimal sequence in this model as an open question. Here we resolve this question by providing an efficient algorithm to construct optimal sequences; our algorithm has a polynomial running time, and performs very efficiently in practice. We illustrate the implementation of our method on structures drawn from the Protein Data Bank. We also consider extensions of the model to larger amino acid alphabets, as a way to overcome the limitations of the binary H/P alphabet. We show that for a natural class of arbitrarily large alphabets, it remains possible to design optimal sequences efficiently. Finally, we analyze some of the consequences of this sequence design model for the study of evolutionary fitness landscapes. A given target structure may have many sequences that are optimal in the model of Sun et al.; following a notion raised by the work of J. Maynard Smith, we can ask whether these optimal sequences are "connected" by successive point mutations. We provide a polynomial-time algorithm to decide this connectedness property, relative to a given target structure. We develop the algorithm by first solving an analogous problem expressed in terms of submodular functions, a fundamental object of study in combinatorial optimization.

Algorithms↗
PubMed2004

SNAP: workbench management tool for evolutionary population genetic analysis.

UNLABELLED: The reconstruction of population processes from DNA sequence variation requires the coordinated implementation of several coalescent-based methods, each bound by specific assumptions and limitations. In practice, the application of these coalescent-based methods for parameter estimation is difficult because they make strict assumptions that must be verified a priori and their parameter-rich nature makes the estimation of all model parameters very complex and computationally intensive. A further complication is their distribution as console applications that require the user to navigate through console menus or specify complex command-line arguments. To facilitate the implementation of these coalescent-based tools we developed SNAP Workbench, a Java program that manages and coordinates a series of programs. The workbench enhances population parameter estimation by ensuring that the assumptions and program limitations of each method are met and by providing a step-by-step methodology for examining population processes that integrates both summary-statistic methods and coalescent-based population genetic models. AVAILABILITY: SNAP Workbench is freely available at http://snap.cifr.ncsu.edu. The workbench and tools can be downloaded for Mac, Windows and Unix operating systems. Each package includes installation instructions, program documentation and a sample dataset. SUPPLEMENTARY INFORMATION: A description of system requirements and installation instructions can be found at http://snap.cifr.ncsu.edu.

Computer Simulation↗
PubMed1999

Structure-function analysis of an evolutionary conserved protein, DAP3, which mediates TNF-alpha- and Fas-induced cell death.

A novel approach to the isolation of positive mediators of programmed cell death, based on random inactivation of genes by expression of anti sense RNAs, was employed to identify mediators of interferon-gamma-induced apoptosis. One of the several genes identified is DAP3, which codes for a 46 kDa protein with a potential nucleotide-binding motif. Structure-function studies of the protein indicate that the intact full-length protein is required for its ability to induce apoptosis when overexpressed. The N-terminal 230 amino acids, on the other hand, act in a dominant-negative fashion. Both of these functions are dependent on the integrity of the nucleotide binding motif. Expression of anti-sense DAP3 RNA and of the dominant interfering form of DAP3 both protected cells from apoptosis induced by activation of Fas and tumor necrosis factor alpha (TNF-alpha) receptors. Thus, DAP3 is implicated as a positive mediator of these death-inducing stimuli. It functions downstream of the receptor signaling complex and its death promoting effects depend on caspase activity. In the nematode Caenorhabditis elegans, a potential homolog of DAP3 showing 35% identity and 64% similarity to the human protein was isolated. Overexpression of the nematode DAP3 cDNA in mammalian cells induced cell death, indicating that the protein is conserved at the functional level as well as the structural level.

Amino Acid Sequence↗
PubMed2000

Ultrastructure of the post-corpus of Zeldia punctata (Cephalobina) for analysis of the evolutionary framework of nematodes related to Caenorhabditis elegans (Rhabditina).

The ultrastructure of the post-corpus of Zeldia punctata (Cephalobina) was compared with previous observations of Caenorhabditis elegans (Rhabditina) and Diplenteron sp. (Diplogastrina) with the goal of interpreting the morphological evolution of the feeding structures in the Secernentea. The post-corpus of Z. punctata consists of six marginal, 13 muscle, five gland and seven nerve cells. The most anterior of four layers of muscle cells consists of six mononucleate cells in Z. punctata. The homologous layer in C. elegans and Diplenteron consists of three binucleate cells, suggesting a unique derived character (synapomorphy) shared between the Rhabditina and Diplogastrina. Contrary to Diplenteron sp. where we observed three oesophageal glands, Z. punctata and C. elegans have five oesophageal glands. We question this shared character as reflecting a common evolution between the Cephalobina and Rhabditina, because there are strong arguments for functional (adaptive) convergence of the five glands in these bacterial feeders. Convergence is further suggested by the mosaic distribution of three versus five glands throughout the Nemata; this distribution creates difficulties in establishing character polarity. Although morphological data are often laborious to recover and interpret, we nevertheless view 'reciprocal illumination' between molecular and morphological characters as the most promising and robust process for reconstructing the evolution of the Secernentea and its feeding structures.

Animals↗
PubMed1999

Analysis of Frankia evolutionary radiation using glnII sequences.

Using a glnII (encoding glutamine synthetase II) PCR selective screening, a Frankia ACN14a gene library clone was isolated. A derived glnII-hybridising 2.7-kb HindIII subclone was characterised. Identities of 95% and 93% were observed, respectively, with the corresponding Frankia CpI1 glnI and glnII regions. A variable segment of the glnII region was selected, PCR amplified from various Frankia genomes, sequenced, and used to investigate phylogenetic relationships within the genus. glnII phylogenetic inferences are well-resolved and allowed us to deduce evolutionary trends among Frankia. Frankia radiation seems to begin with a diversification according to the ability or not to infect actinorhizal plants. The infective strains are divided into two clusters matching plant-colonising specificities.

Actinomycetales↗
PubMed1994

A cladistic analysis of the evolutionary relationships of the members of the tyrosinase gene family using sequence data.

Recently, DNA sequence data have been published on tyrosinase and tyrosinase-related proteins (TRPs) in a wide variety of vertebrates ranging from Rana to Homo. These proteins are in turn members of a larger family of binuclear copper-binding proteins, which all contain two highly conserved copper-binding domains. This gene family also includes tyrosinases from fungi and bacteria as well as arthropodan and molluscan hemocyanins. Parsimony-based alignment and tree construction algorithms (Malign, v1.85 and PAUP, 3.1.1) were used to analyze the diversification of both the evolutionarily conserved copper-binding domains in copper-binding proteins in general as well as the diversification of the vertebrate tyrosinase gene family more specifically. These analyses show that the diversification of the vertebrate tyrosinase gene family minimally predates the diversification of vertebrates. Vertebrate tyrosinases proper first diverged from an ancestral tyrosinase-related protein (TRP) that then subsequently diverged to form tyrosinase-related protein-1s (TRP-1s) and tyrosinase-related protein-2s (TRP-2s).

Algorithms↗
PubMedDate not supplied

Health/Illness transition and telehealth: a concept analysis using the evolutionary method.

TOPIC: Telehealth as an alternative to hospitalization. PURPOSE: Exploring the health/illness transition that occurs when an acutely ill client may be discharged into the home with telehealth in place of hospitalization or in an effort to promote an earlier discharge from the hospital. SOURCE: Published literature. CONCLUSION: The concept of the health/illness transition using telehealth has not been researched. Qualitative methods of research using interviews could enhance the knowledge in selecting appropriate individuals and nursing interventions to enhance the clients' transition from the hospital to the home with telehealth.

Acute Disease↗
PubMed1999

Population genetic and evolutionary approaches to analysis of Neisseria meningitidis isolates belonging to the ET-5 complex.

Periodically, new disease-associated variants of the human pathogen Neisseria meningitidis arise. These meningococci diversify during spread, and related isolates recovered from different parts of the world have different genetic and antigenic characteristics. An example is the ET-5 complex, members of which were isolated globally from the mid-1970s onwards. Isolates from a hyperendemic outbreak of meningococcal disease in Worcester, England, during the late 1980s were characterized by multilocus sequence typing and sequence determination of antigen genes. These data established that the Worcester outbreak was caused by ET-5 complex meningococci which were not closely related to the ET-5 complex bacteria responsible for a hyperendemic outbreak in the nearby town of Stroud during the years preceding the Worcester outbreak. A comparison with other ET-5 complex meningococci established that there were at least three distinct globally distributed subpopulations within the ET-5 complex, characterized by particular housekeeping and antigen gene alleles. The Worcester isolates belonged to one of these subpopulations, the Stroud isolates belonged to another, and at least one representative of the third subpopulation identified in this work was isolated elsewhere in the United Kingdom. The sequence data demonstrated that ET-5 variants have arisen by multiple complex pathways involving the recombination of antigen and housekeeping genes and de novo mutation of antigen genes. The data further suggest that either the ET-5 complex has been in existence for many years, evolving and spreading relatively slowly until its disease-causing potential was recognized, or it has evolved and spread rapidly since its first identification in the 1970s, with each of the subpopulations attaining a distribution spanning several continents.

Amino Acid Sequence↗
PubMed1996

Phylogenetic analysis in molecular evolutionary genetics.

Recent developments of statistical methods in molecular phylogenetics are reviewed. It is shown that the mathematical foundations of these methods are not well established, but computer simulations and empirical data indicate that currently used methods such as neighbor joining, minimum evolution, likelihood, and parsimony methods produce reasonably good phylogenetic trees when a sufficiently large number of nucleotides or amino acids are used. However, when the rate of evolution varies extensively from branch to branch, many methods may fail to recover the true topology. Solid statistical tests for examining the accuracy of trees obtained by neighbor joining, minimum evolution, and least-squares method are available, but the methods for likelihood and parsimony trees are yet to be refined. Parsimony, likelihood, and distance methods can all be used for inferring amino acid sequences of the proteins of ancestral organisms that have become extinct.

DNA↗
PubMed2004

An evolutionary and functional analysis of FoxL2 in rainbow trout gonad differentiation.

FOXL2 is a forkhead transcription factor involved in ovarian development and function. Here, we have studied the evolution and pattern of expression of the FOXL2 gene and its paralogs in fish. We found well conserved FoxL2 sequences (FoxL2a) and divergent genes, whose forkhead domains belonged to the class L2 and were shown to be paralogs of the FoxL2a sequences (named FoxL2b). In the rainbow trout, FoxL2a and FoxL2b were specifically expressed in the ovary, but displayed different temporal patterns of expression. FoxL2a expression correlated with the level of aromatase, the key enzyme in estrogen production, and an estrogen treatment used to feminize genetically male individuals elicited the up-regulation of both paralogs. Conversely, androgens or an aromatase inhibitor down-regulated FoxL2a and FoxL2b in females. We speculate that there is a direct link between estrogens and FoxL2 expression in fish, at least during the period where the identity of the gonad is sensitive to hormonal treatments.

Animals↗
PubMed1983

[Neurologic status of the human fetus during labor and analysis from an evolutionary standpoint].

A study of the human fetus in 62 deliveries (at the moment of head birth and in the first seconds after complete birth up to the onset of pulmonary respiration) revealed that its neurologic status is characterized by muscular atonia, by the absence of spontaneous movements, proprioceptive and exteroceptive reflexes, as well as by the absence of reactions to needle puncture, light, sound and olfactory irritations. The suggestion is substantiated that phenomenal peculiarities of the neurologic status of the fetus during parturition are occasioned by the state of hibernation (autohibernation) secondary to shifts at the level of biologically active substances in the "parturient-placenta-fetus" system.

Animals↗
PubMed1993

Structural organization of the gene encoding the rat pancreatitis-associated protein. Analysis of its evolutionary history reveals an ancient divergence from the other carbohydrate-recognition domain-containing genes.

Rat pancreatitis-associated protein (PAP) mRNA is barely detectable in normal pancreas and overexpressed during acute pancreatitis (Iovanna, J., Orelle, B., Keim, V., and Dagorn J.-C. (1991) J. Biol. Chem. 266, 24664-24669). RNA amplification by reverse-transcriptase-coupled polymerase chain reaction showed that PAP mRNA was constitutively expressed in duodenum, jejunum, and ileum, at similar levels as in pancreas during the acute phase of pancreatitis. A weak expression was also detected in several other tissues. The rat PAP gene was isolated from a genomic library and characterized over 3.2 kilobases of gene sequence and 1.2 kilobases of 5'-flanking sequence. The 5' end of the coding sequence was determined by primer extension of the PAP transcript. Several potential regulatory elements were identified in the promoter region, including a pancreas-specific consensus sequence, two Pan1 (pancreas-specific) transcription activators, two IL-6 response elements, and one glucocorticoid response element. The PAP coding sequence spanned over six exons. The first three exons encoded the 5'-untranslated region of the mRNA, the signal peptide, and 39 amino acids of the NH2-terminal end of the mature protein, respectively. The other three exons encoded a domain of the protein with significant homology to the carbohydrate-recognition domain of animal lectins. Sequence comparison of the PAP gene with 13 carbohydrate-recognition domain-containing genes revealed that they derived from the same ancestor gene. Position of introns within the carbohydrate-recognition domain were different, however, suggesting that PAP belongs to a new group of lectins. These results support the hypothesis that genes encoding PAP and other lectins evolved from a common ancestor gene by intron gain.

Acute Disease↗
PubMed2002

Hepatitis C virus evolutionary patterns studied through analysis of full-genome sequences.

The evolutionary patterns of hepatitis C virus (HCV), including the best-fitting nucleotide substitution model and the molecular clock hypothesis, were investigated by analyzing full-genome sequences available in the HCV database. The likelihood ratio test allowed us to discriminate among different evolutionary hypotheses. The phylogeny of the six major HCV types was accurately inferred, and the final tree was rooted by reconstructing the hypothetical HCV common ancestor with the maximum likelihood method. The presence of phylogenetic noise and the relative nucleotide substitution rates in the different HCV genes were also examined. These results offer a general guideline for the future of HCV phylogenetic analysis and also provide important insights on HCV origin and evolution.

Biological Evolution↗