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Concerted gene duplications in the two keratin gene families.

Evolutionary trees were derived from the keratin protein sequences using the Phylogeny Analysis Using Parsimony (PAUP) set of programs. Three major unexpected conclusions were derived from the analysis: The smallest keratin protein subunit, K#19 (Moll et al. 1982), is not the most primitive one, but has evolved to fulfill a highly specialized function, presumably to redress the unbalanced synthesis of keratin subunits. Second, the ancestors of keratins expressed in the early embryonic stages, K#8 and K#18, were the first to diverge from the ancestors of all the other keratins. The branches leading to these two keratins are relatively short, indicating a comparatively strong selection against changes in the sequences of these two proteins. Third, the two keratin families show extraordinary parallelism in their patterns of gene duplications. In both families the genes expressed in embryos diverged first, later bursts of gene duplications created the subfamilies expressed in various differentiated cells, and relatively recent gene duplications gave rise to the hair keratin genes and separated the basal cell-specific keratin from those expressed under hyperproliferative conditions. The parallelism of gene duplications in the two keratin gene families implies a mechanism in which duplications in one family influence duplication events in the other family.

Animals↗

Phylogenetic analysis of the homologous proteins of the terminal complement complex supports the emergence of C6 and C7 followed by C8 and C9.

The plasma complement system comprises several activation pathways that share a common terminal route involving the assembly of the terminal complement complex (TCC), formed by C5b-C9. The order of emergence of the homologous components of TCC (C6, C7, C8alpha, C8beta, and C9) has been determined by phylogenetic analyses of their amino acid sequences. Using all the sequence data available for C6-C9 proteins, as well as for perforins, the results suggested that these TCC components originated from a single ancestral gene and that C6 and C7 were the earliest to emerge. Our evidence supports the notion that the ancestral gene had a complex modular composition. A series of gene duplications in combination with a tendency to lose modules resulted in successive complement proteins with decreasing modular complexity. C9 and perforin apparently are the result of different selective conditions to acquire pore-forming function. Thus C9 and perforin are examples of evolutionary parallelism.

Amino Acid Sequence↗

The canary in the mind: on the fate of dreams in psychoanalysis and in contemporary culture.

Dreams have been central in the birth and evolution of psychoanalysis. This paper explores the remarkable story of the relationship between dreams and psychoanalysis as a modern version of the long history of dreams in most healing traditions. But psychoanalysis seems to have turned away from dreams as central inspiration in a way parallel to the general culture's turn away from dreams and the reality of inner life. Yet modern postindustrial culture is transfixed by a version of "dream life" in ways just beginning to be understood (e.g., in the transformation of ancient interest in the inner screen to the external screen). Working with dreams in psychoanalytic psychotherapy was a creative and revolutionary act for our forebears. It is even more so today, in ways that are discussed in this paper.

Culture↗

Autocatalytic sets of proteins.

This article investigates the possibility that the emergence of reflexively autocatalytic sets of peptides and polypeptides may be an essentially inevitable collective property of any sufficiently complex set of polypeptides. The central idea is based on the connectivity properties of random directed graphs. In the set of amino acid monomer and polymer species up to some maximum length, M, the number of possible polypeptides is large, but, for specifiable "legitimate" end condensation, cleavage and transpeptidation exchange reactions, the number of potential reactions by which the possible polypeptides can interconvert is very much larger. A directed graph in which arrows from smaller fragments to larger condensation products depict potential synthesis reactions, while arrows from the larger peptide to the smaller fragments depict the reverse cleavage reactions, comprises the reaction graph for such a system. Polypeptide protoenzymes are able to catalyze such reactions. The distribution of catalytic capacities in peptide space is a fundamental problem in its own right, and in its bearing on the existence of autocatalytic sets of proteins. Using an initial idealized hypothesis that an arbitrary polypeptide has a fixed a priori probability of catalyzing any arbitrary legitimate reaction to assign to each polypeptide those reactions, if any, which it catalyzes, the probability that the set of polypeptides up to length M contains a reflexively autocatalytic subset can be calculated and is a percolation problem on such reaction graphs. Because, as M increases, the ratio of reactions among the possible polypeptides to polypeptides rises rapidly, the existence of such autocatalytic subsets is assured for any fixed probability of catalysis. The main conclusions of this analysis appear independent of the idealizations of the initial model, introduce a novel kind of parallel selection for peptides catalyzing connected sequences of reactions, depend upon a new kind of minimal critical complexity whose properties are definable, and suggest that the emergence of self replicating systems may be a self organizing collective property of critically complex protein systems in prebiotic evolution. Similar principles may apply to the emergence of a primitive connected metabolism. Recombinant DNA procedures, cloning random DNA coding sequences into expression vectors, afford a direct avenue to test the distribution of catalytic capacities in peptide space, may provide a new means to select or screen for peptides with useful properties, and may ultimately lead toward the actual construction of autocatalytic peptide sets.

Amino Acids↗

Extradimensional bypass.

We discuss the concept of extradimensional bypass as it was developed by the late theoretical biologist Michael Conrad. An evolving system that optimizes its performance by gradient ascent (hill climbing) can avoid being trapped in local maxima by increasing the effective dimensionality of its search space. Many local maxima may become saddle points in the higher dimensional space, such that gradient ascent can continue unimpeded. Extradimensional bypass as a concept has parallels in theories of open-ended learning and functional emergence, where new structural, functional, and informational primitives can increase the effective dimensionality of material systems.

Biological Evolution↗

Perspectives on the development of anti-HIV vaccines.

Progress towards the development of a vaccine against acquired immune deficiency syndrome is proceeding along several fronts. First and foremost, it rests on the basic research being done with the virus, particularly its mechanisms of replication, pathogenesis and evolution. More directly, progress comes from studies of animal models with the simian and human immunodeficiency viruses where vaccine candidates have proven effective in blocking infection. Principally because the animal models cannot answer all of the critical questions that apply to a vaccine for man, parallel studies in human volunteers have been initiated.

AIDS Vaccines↗

Molecular markers for predicting recurrence, progression and outcomes of bladder cancer (do the poster boys need new posters?).

PURPOSE OF REVIEW: Molecular markers for bladder cancer recurrence and progression continue to drive many research programmes. Translating the laboratory findings into the clinical environment where these markers are used in clinical decision making has proved problematic. In the clinical arena, stage and grade are still the main focus for decisions about patient management. There is however an evolution in bladder cancer research from single-marker/single-pathway research to a more global assessment of the tumour cell with DNA microarrays and proteomics. RECENT FINDINGS: In the last year, DNA microarray assessment has revealed several interesting molecular markers such as p33ING1 and DEK. Parallel "conventional" single-pathway research has focused on new novel markers such as HER2/neu, survivin and matrix metalloproteinase 2 (MMP-2). Molecular markers that have a long-standing association with bladder cancer progression such as p53, E-cadherin and Ki-67 have been reviewed by both single-marker studies and by microarray studies and their status remains important. SUMMARY: It is an exciting time in the molecular biology research of bladder cancer as the focus changes to assess the global genetic and protein expression within tumour cells. From such a wealth of information it is likely that molecular markers will make the translation from benchside to bedside.

Biomarkers, Tumor↗

Ocular surface temperature: a review.

PURPOSE: To review the evolution in ocular temperature measurement during the last century and examine the advantages and applications of the latest noncontact techniques. The characteristics and source of ocular surface temperature are also discussed. METHODS: The literature was reviewed with regard to progress in human thermometry techniques, the parallel development in ocular temperature measurement, the current use of infrared imaging, and the applications of ocular thermography. RESULTS: It is widely acknowledged that the ability to measure ocular temperature accurately will increase the understanding of ocular physiology. There is a characteristic thermal profile across the anterior eye, in which the central area appears coolest. Ocular surface temperature is affected by many factors, including inflammation. In thermometry of the human eye, contact techniques have largely been superseded by infrared imaging, providing a noninvasive and potentially more accurate method of temperature measurement. Ocular thermography requires high resolution and frame rate: features found in the latest generation of cameras. Applications have included dry eye, contact lens wear, corneal sensitivity, and refractive surgery. CONCLUSIONS: Interest in the temperature of the eye spans almost 130 years. It has been an area of research largely driven by prevailing technology. Current instrumentation offers the potential to measure ocular surface temperature with more accuracy, resolution, and speed than previously possible. The use of dynamic ocular thermography offers great opportunities for monitoring the temperature of the anterior eye.

Body Temperature↗

Antigenic and genetic diversity among swine influenza A H1N1 and H1N2 viruses in Europe.

Three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, co-evolve in pigs in Europe. H1N2 viruses isolated from pigs in France and Italy since 1997 were closely related to the H1N2 viruses which emerged in the UK in 1994. In particular, the close relationship of the neuraminidases (NAs) of these viruses to the NA of a previous UK H3N2 swine virus indicated that they had not acquired the NA from H3N2 swine viruses circulating in continental Europe. Moreover, antigenic and genetic heterogeneity among the H1N2 viruses appeared to be due in part to multiple introductions of viruses from the UK. On the other hand, comparisons of internal gene sequences indicated genetic exchange between the H1N2 viruses and co-circulating H1N1 and/or H3N2 subtypes. Most genes of the earlier (1997-1998) H1N2 isolates were more closely related to those of a contemporary French H1N1 isolate, whereas the genes of later (1999-2000) isolates, including the HAs of some H1N2 viruses, were closely related to those of a distinct H1N1 antigenic variant which emerged in France in 1999. In contrast, an H3N2 virus isolated in France in 1999 was closely related antigenically and genetically to contemporary human A/Sydney/5/97-like viruses. These studies reveal interesting parallels between genetic and antigenic drift of H1N1 viruses in pig and human populations, and provide further examples of the contribution of genetic reassortment to the antigenic and genetic diversity of swine influenza viruses and the importance of the complement of internal genes in the evolution of epizootic strains.

Animals↗

Functional implications of structure-based sequence alignment of proteins in the extracellular pectate lyase superfamily.

Pectate lyases are plant virulence factors that degrade the pectate component of the plant cell wall. The enzymes share considerable sequence homology with plant pollen and style proteins, suggesting a shared structural topology and possibly functional relationships as well. The three-dimensional structures of two Erwinia chrysanthemi pectate lyases, C and E, have been superimposed and the structurally conserved amino acids have been identified. There are 232 amino acids that superimpose with a root-mean-square deviation of 3 A or less. These amino acids have been used to correct the primary sequence alignment derived from evolution-based techniques. Subsequently, multiple alignment techniques have allowed the realignment of other extracellular pectate lyases as well as all sequence homologs, including pectin lyases and the plant pollen and style proteins. The new multiple sequence alignment reveals amino acids likely to participate in the parallel beta helix motif, those involved in binding Ca2+, and those invariant amino acids with potential catalytic properties. The latter amino acids cluster in two well-separated regions on the pectate lyase structures, suggesting two distinct enzymatic functions for extracellular pectate lyases and their sequence homologs.

Amino Acid Sequence↗

Origins of DNA replication in the three domains of life.

Replication of DNA is essential for the propagation of life. It is somewhat surprising then that, despite the vital nature of this process, cellular organisms show a great deal of variety in the mechanisms that they employ to ensure appropriate genome duplication. This diversity is manifested along classical evolutionary lines, with distinct combinations of replicon architecture and replication proteins being found in the three domains of life: the Bacteria, the Eukarya and the Archaea. Furthermore, although there are mechanistic parallels, even within a given domain of life, the way origins of replication are defined shows remarkable variation.

Archaea↗

Purification and properties of reptilian and amphibian growth hormones.

Highly purified growth hormone was isolated from the pituitaries of two reptilian species, the snapping turtle and the sea turtle, and two amphibian species, the bullfrog and the leopard frog. Characterization studies were performed with these growth hormones in comparison with mammalian and avian growth hormones. Great similarities among these species were found in chromatographic behavior, Ve/Vo ratios (2.0) on gel filtration, disc electrophoretic patterns, terminal amino acid residues and immunochemical reactivity with snapping turtle growth hormone antiserum. Species differences were noted in amino acid composition and immunoactivity measured by rat growth hormone antiserum, and these appeared to reflect the phylogenetic relationships among the four tetrapod species. The turtle and frog growth hormones gave parallel dose responses in the rat tibia assay. All were less potent than the bovine growth hormone standard except the bullfrog growth hormone which was equipotent if not more active. The data indicate that many elements of growth hormone structure have been strongly conserved during evolution.

Amino Acid Sequence↗

Genetic evidence that two types of retroelements evolved through different pathways in ectomycorrhizal homobasidiomycetes Tricholoma spp.

We designed a polymerase chain reaction that allows us to clone two types of putative reverse transcriptase genes from 11 species of ectomycorrhizal basidiomycetes that belong to the genus Tricholoma. One corresponds to the putative gene of marY1, a long terminal repeat (LTR) retroelement from Tricholoma matsutake, and the other, marY2N, a LINE-like non-LTR (L1-like) retroelement from this fungus. Putative protein products predicted from nucleotide sequencing of cloned fragments were phylogenetically analyzed. marY1-like elements had a parallel phylogenetic relationship with no apparent correlation to a current taxonomic profile, while marY2N-like elements showed a vertical one in relation to host-plant species. Data suggest that marY1-like elements and marY2N-like elements have evolved independently, and the evolution of marY1-like elements could have occurred later than the evolution of marY2N-like elements in the species of Tricholoma.

Amino Acid Sequence↗

Directed evolution of a fungal peroxidase.

The Coprinus cinereus (CiP) heme peroxidase was subjected to multiple rounds of directed evolution in an effort to produce a mutant suitable for use as a dye-transfer inhibitor in laundry detergent. The wild-type peroxidase is rapidly inactivated under laundry conditions due to the high pH (10.5), high temperature (50 degrees C), and high peroxide concentration (5-10 mM). Peroxidase mutants were initially generated using two parallel approaches: site-directed mutagenesis based on structure-function considerations, and error-prone PCR to create random mutations. Mutants were expressed in Saccharomyces cerevisiae and screened for improved stability by measuring residual activity after incubation under conditions mimicking those in a washing machine. Manually combining mutations from the site-directed and random approaches led to a mutant with 110 times the thermal stability and 2.8 times the oxidative stability of wild-type CiP. In the final two rounds, mutants were randomly recombined by using the efficient yeast homologous recombination system to shuffle point mutations among a large number of parents. This in vivo shuffling led to the most dramatic improvements in oxidative stability, yielding a mutant with 174 times the thermal stability and 100 times the oxidative stability of wild-type CiP.

Coprinus↗

Comprehensive analysis of two Alu Yd subfamilies.

Alu elements have inserted in the human genome throughout primate evolution. A small number of Alu insertions have occurred after the divergence of humans from nonhuman primates and therefore should not be present in nonhuman primate genomes. Most of these recently integrated Alu elements are contained with a series of discrete Alu subfamilies that are related to each other based upon diagnostic nucleotide substitutions. We have extracted members of the Alu Yd subfamily that are derivatives of the Alu Y subfamily that share a common 12-bp deletion that defines the Yd lineage from the draft sequence of the human genome. Analysis of the Yd Alu elements resulted in the recovery of two new Alu subfamilies, Yd3 and Yd6, which contain a total of 295 members (198 Yd3 and 97 Yd6). DNA sequence analysis of each of the Alu Yd subfamilies yielded age estimates of 8.02 and 1.20 million years old for the Alu Yd3 and Yd6 subfamilies, respectively. Two hundred Alu Yd3 and Yd6 loci were screened using polymerase chain reaction (PCR) assays to determine their phylogenetic origin and associated levels of human genomic diversity. The Alu Yd3 subfamily appears to have started amplifying relatively early in primate evolution and continued propagating albeit at a low level as many of its members are found in a variety of hominoid (humans, greater and lesser ape) genomes. Only two of the elements are polymorphic in the human genome and absent from the genomes of nonhuman primates. By contrast all of the members of the Alu Yd6 subfamily are restricted to the human genome, with 12% of the elements representing insertion polymorphisms in human populations. A single Alu Yd6 locus contained an independent parallel forward insertion of a paralogous Alu Sq sequence in the owl monkey. These Alu subfamilies are a source of genomic fossil relics for the study of primate phylogenetics and human population genetics.

Alu Elements↗

Sexual dimorphism in primate evolution.

Sexual dimorphism is a pervasive phenomenon among anthropoid primates. Comparative analyses over the past 30 years have greatly expanded our understanding of both variation in the expression of dimorphism among primates, and the underlying causes of sexual dimorphism. Dimorphism in body mass and canine tooth size is familiar, as is pelage and "sex skin" dimorphism. More recent analyses are documenting subtle differences in the pattern of skeletal dimorphism among primates. Comparative analyses have corroborated the sexual selection hypotheses, and have provided a more detailed understanding of the relationship between sexual selection, natural selection, and mating systems in primates. A clearer picture is emerging of the relative contribution of various selective and nonselective mechanisms in the evolution and expression of dimorphism. Most importantly, recent studies have shown that dimorphism is the product of changes in both male and female traits. Developmental studies demonstrate the variety of ontogenetic pathways that can lead to dimorphism, and provide additional insight into the selective mechanisms that influence dimorphism throughout the lifetime of an animal. Evidence from the fossil record suggests that dimorphism probably evolved in parallel twice, and the dimorphism in some extinct hominoids probably exceeded that of any living primate. Our advances in understanding the behavioral/ecological correlates of dimorphism in living primates have not improved our ability to reconstruct social systems in extinct species on the basis of dimorphism alone, beyond the inference of polygyny or intense male-male competition. However, our understanding of the behavioral/ecological correlates of growth and development, and of the expression of dimorphism as a function of separate changes in male and female traits, offers great potential for inferring evolutionary changes in behavior over time.

Animals↗

Evolution of genome size in Drosophila. is the invader's genome being invaded by transposable elements?

Genome size varies considerably between species, and transposable elements (TEs) are known to play an important role in this variability. However, it is far from clear whether TEs are involved in genome size differences between populations within a given species. We show here that in Drosophila melanogaster and Drosophila simulans the size of the genome varies among populations and is correlated with the TE copy number on the chromosome arms. The TEs embedded within the heterochromatin do not seem to be involved directly in this phenomenon, although they may contribute to differences in genome size. Furthermore, genome size and TE content variations parallel the worldwide colonization of D. melanogaster species. No such relationship exists for the more recently dispersed D. simulans species, which indicates that a quantitative increase in the TEs in local populations and fly migration are sufficient to account for the increase in genome size, with no need for an adaptation hypothesis.

Animals↗

Structure, function and evolution of the Archaeal class I fructose-1,6-bisphosphate aldolase.

FBPA (fructose-1,6-bisphosphate aldolase) catalyses the reversible aldol condensation of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate to form fructose 1,6-bisphosphate. Two classes of FBPA, which rely on different reaction mechanisms, have so far been discovered, class I mainly found in Eucarya and class II mainly in Bacteria. Only recently were genes encoding proteins with FBPA activity identified in Archaea. Archaeal FBPAs do not share any significant overall sequence identity with members of the traditional classes of FBPAs, raising the interesting question of whether they have evolved independently by convergent evolution or diverged from a common ancestor. Biochemical characterization of FBPAs of the two hyperthermophilic Archaea Thermoproteus tenax and Pyrococcus furiosus showed that the enzymes use a Schiff-base mechanism and thus belong to the class I aldolases. The crystal structure of the archaeal FBPA from T. tenax revealed that the protein fold, as for the classical FBPA I and II, is that of a parallel (betaalpha)(8) barrel. A substrate-bound crystal structure allowed detailed active-site comparisons which showed the conservation of six important catalytic and substrate-binding residues between the archaeal and the classical FBPA I. This observation provides further evidence that the two sequence families of proteins share a common evolutionary origin. Furthermore, structure and sequence analysis indicate that the class I FBPA shares a common evolutionary origin with several other enzyme superfamilies of the (betaalpha)(8) barrel fold.

Aeropyrum↗