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Sequence patterns derived from the automated prediction of functional residues in structurally-aligned homologous protein families.

MOTIVATION: Most proteins have evolved to perform specific functions that are dependent on the adoption of well-defined three-dimensional (3D) structures. Specific patterns of conserved residues in amino acid sequences of divergently evolved proteins are frequently observed; these may reflect evolutionary restraints arising both from the need to maintain tertiary structure and the requirement to conserve residues more directly involved in function. Databases of such sequence patterns are valuable in identifying distant homologues, in predicting function and in the study of evolution. RESULTS: A fully automated database of protein sequence patterns, Functional Protein Sequence Pattern Database (FPSPD), has been derived from the analysis of the conserved residues that are predicted to be functional in structurally aligned homologous families in the HOMSTRAD database. Environment-dependent substitution tables, evolutionary trace analysis, solvent accessibility calculations and 3D-structures were used to obtain the FPSPD. The method yielded 3584 patterns that are considered functional and 3049 patterns that are probably functional. FPSPD could be useful for assigning a protein to a homologous superfamily and thereby providing clues about function. AVAILABILITY: FPSPD is available at http://www-cryst.bioc.cam.ac.uk/~fpspd/

Algorithms↗

A survey of methods for classification of gene expression data using evolutionary algorithms.

The rapid increase in the quantity of available biologic data over the last decade, brought about by the introduction of massively parallel methods for gene expression measurements, has highlighted the need for more efficient computational techniques for analysis. This paper reviews the use of evolutionary algorithms (EAs) in connection with classification based on gene expression data matrices. Brief introductions to data classification methods and EAs are given, followed by a survey of studies dealing with the application of evolutionary algorithms to various (cancer related) data sets. The general conclusion, based on the published results surveyed here, is that EAs may constitute an efficient method for optimal gene selection, and can also help in reducing the size (number of features used) of classifiers. In many cases, the classification accuracy obtained using EAs, often in conjunction with other methods, represents a significant improvement over results obtained without the use of EAs. However, long-term, independent clinical follow-up studies will be essential to validate prognostic markers identified by the use of EA-based methods.

Algorithms↗

Evolutionary dynamics of functionally constrained phenotypic characters.

A nonlinear analysis is performed, employing the theory of Lyapunov functions, to examine the relative importance of genetic and phenotypic covariance matrices for the evolution of functionally coupled quantitative traits in an adaptive topography with several directions of increasing fitness. The analysis is based on Lande's evolution equations for phenotypic characters. It is supposed that evolution of a set of functionally constrained characters far from equilibrium corresponds to evolution along a ridge in the fitness landscape. It is shown that the pattern of variation and covariation restricts the possible directions of evolutionary change in the following sense. Any population starting sufficiently near the ridge will evolve along it, provided that one eigenvector of the genetic covariance matrix and one eigenvector of the phenotypic covariance matrix point into the direction of the ridge. Otherwise, the set of initial positions of a population enabling evolution along the ridge is more or less restricted, depending on the degree of deviation of the eigenvectors from the direction of the ridge. Moreover, too much phenotypic variance of the characters under stabilizing selection may inhibit any evolution along the ridge. Thus, the present analysis establishes population-genetic prerequisites and constraints for the evolution of functionally constrained phenotypic traits.

Biological Evolution↗

Absorption microspectroscopy, theory and applications in the case of the photosynthetic compartment.

We performed microspectroscopic evaluation of the pigment composition of the photosynthetic compartments of both algae and higher plants. The feasibility of microspectroscopy for discriminating among species and/or phylogenetic groups was tested on laboratory cultures. Gaussian bands decompositions, and a fitting algorithm, together with fourth-derivative transformation of absorbance spectra, provided a reliable discrimination among chlorophylls, phycobiliproteins and carotenoids. Comparative analysis of absorption spectra highlighted the evolutionary grouping of the algae into three main lineages in accordance with the most recent endosymbiotic theories.

Biological Evolution↗

Diversity and evolutionary history of endogenous retroviruses in the genome of Manis pentadactyla.

Endogenous retroviruses (ERVs), remnants of ancient viral infections integrated into host genomes, serve as invaluable molecular fossils for studying viral evolution. In this study, we performed a genomic analysis of the Chinese pangolin (Manis pentadactyla), identifying novel full-length endogenous retroviruses, designated as Manis pentadactyla ERVs (MPERVs). MPERVs span three retroviral genera: Alpha-, Beta-, and Gamma-retroviruses. Using genomic screening and phylogenetic analysis, we classified MPERVs and reconstructed their evolutionary history, uncovering evidence of complex recombination events and cross-species transmission. Estimated insertion times for MPERVs range from very recent to 18.38 million years ago. MPERVs exhibit diverse structural features, notably including conserved retroviral domains and functional motifs and highlighting their preservation across extensive evolutionary periods. These findings shed light on the evolutionary dynamics of ERVs in Chinese pangolin and suggest the potential for expanded host ranges among certain retrovirus genera.IMPORTANCEEndogenous retroviruses are unique viruses distinguished by the fact that they are retained as part of the host genome after an exogenous retrovirus infects the host. The Chinese pangolin, as a host with a long independent evolutionary history, likely holds valuable insights in its genome regarding retrovirus endogenization and transmission. In this study, we identified the footprints of exogenous retroviruses from three different genera in the pangolin genome: Alpharetrovirus, Betaretrovirus, and Gammaretrovirus. Additionally, by calculating the integration times of the pangolin's endogenous retroviruses and analyzing the domains of the three main functional proteins (GAG, POL, and ENV), we found that the insertions are relatively young. This suggests that these endogenous retroviruses infected the Chinese pangolin long before their endogenization. This study represents the exploration of endogenous retroviruses in the Chinese pangolin genome, expanding our understanding of endogenous retroviruses in mammals. Furthermore, our findings provide new evidence for the phenomenon of the cross-species transmission of retroviruses prior to endogenization.

Endogenous Retroviruses↗

Evolution of the cystatin B gene: implications for the origin of its variable dodecamer tandem repeat in humans.

The human cystatin B gene contains a variable number of 12-bp tandem repeats in its promoter region, of which the common alleles contain two or three copies and unusual expansion causes progressive myoclonus epilepsy of the Unverricht-Lundborg type. We undertook a comprehensive analysis of the genomic sequence to address the evolutionary events of this variable repeat. By examination of a contiguous genome sequence spanning 5.0 kb and linkage analysis of detected polymorphic changes, we identified six major intragenic haplotypes in unrelated Japanese subjects. The number of normal repeats was closely correlated with these alleles, indicating that changes in the array should be comparatively rare events during human evolution. To examine the origin of the repeat array further, we also analyzed five primate genomes. Repetitive polymorphism was unlikely in hominoids, and the array originated with the dodecamer itself in the course of primate evolution. The variability conceivably developed after the separation to humans.

Cystatin B↗

Design principles underlying circadian clocks.

A fundamental problem for regulatory networks is to understand the relation between form and function: to uncover the underlying design principles of the network. Circadian clocks present a particularly interesting instance, as recent work has shown that they have complex structures involving multiple interconnected feedback loops with both positive and negative feedback. While several authors have speculated on the reasons for this, a convincing explanation is still lacking. We analyse both the flexibility of clock networks and the relationships between various desirable properties such as robust entrainment, temperature compensation, and stability to environmental variations and parameter fluctuations. We use this to argue that the complexity provides the flexibility necessary to simultaneously attain multiple key properties of circadian clocks. As part of our analysis we show how to quantify the key evolutionary aims using infinitesimal response curves, a tool that we believe will be of general utility in the analysis of regulatory networks. Our results suggest that regulatory and signalling networks might be much less flexible and of lower dimension than their apparent complexity would suggest.

Animals↗

[Stellar spectral recognition based on wavelet de-noising and SVM].

The present paper describes a new technique for stellar spectral recognition. Considering the characteristics of stellar spectral data, support vector machine (SVM) was adopted to build a recognition system as kernel. Because stellar spectral data sets are usually extremely noisy, the correct classification rate of direct applying SVM is low. Consequently, wavelet de-noising method was proposed to reduce noise first and extract the main characteristics of stellar spectra. Then SVM was used for the recognition. Based on the real-world stellar spectra contributed by Jacoby et al. (1984), it has proven that there will be a better performance using this composite classifier which combines wavelet and SVM than using SVM with principle component analysis data dimension reduction technique. From the experiment of comparison of discriminant analysis and SVM based on stellar spectra for evolutionary synthesis, we can see that the correct classification rate of SVM is higher than that of discriminant analysis methods, and a well generalization ability is achieved.

English Abstract↗

Molecular phylogeny of extant gymnosperms and seed plant evolution: analysis of nuclear 18S rRNA sequences.

To study the evolutionary relationships among the four living gymnosperm orders and the interfamilial relationships in each order, a set of 65 nuclear 18S rRNA sequences from ferns, gymnosperms, and angiosperms was analyzed using the neighbor-joining and maximum-parsimony methods. With Selaginella as the outgroup, the analysis strongly indicates that the seed plants form a monophyletic group with the ferns as a sister group. Within the seed plants the angiosperms are clearly a monophyletic group. Although the bootstrap support for the monophyly of the gymnosperm clade is moderate, the monophyly is further supported by its lack of angiosperm-specific indels. Within the gymnosperms there appear to be three monophyletic clades: Cycadales-Ginkgoales, Gnetales, and Coniferales. The cycad-ginkgo clade is the earliest gymnosperm lineage. Given the strong support for the sister group relationship between Gnetales and Coniferales, it is unlikely that Gnetales is a sister group of the angiosperms, contrary to the view of many plant taxonomists. Within Coniferales, Pinaceae is monophyletic and basal to the remaining conifer families, among which there are three monophyletic clades: Phyllocladaceae-Podocarpaceae, Araucariaceae, and Sciadopityaceae-Taxaceae-Cephalotaxaceae-Taxodiacea e-Cupressaceae. Within the latter clade, Sciadopityaceae may be an outgroup to the other four families. Among the angiosperms, no significant cluster at the level of subclass was found, but there was evidence that Nymphaeaceae branched off first. Within the remaining angiosperms, the monocots included in this study are nested and form a monophyletic group. This study attests to the utility of nuclear 18S rRNA sequences in addressing relationships among living gymnosperms. Considerable variation in substitution rates was observed among the ferns and seed plants.

Evolution, Molecular↗

Molecular characterization and baculovirus expression of the glycoprotein B of a seal herpesvirus (phocid herpesvirus-1).

A glycoprotein B (gB) gene homologue was identified in a 5.4-kb BamHl genomic fragment of the phocid herpesvirus type-1 (PhHV-1) which represents a widespread and important pathogen of pinnipeds. Sequence analysis revealed a gB-specific open-reading frame comprising 881 amino acids. Phylogenetic analysis gave evidence for a close evolutionary relationship between PhHV-1 and members of the Varicellovirus genus of the alpha-Herpesvirinae and canid herpesvirus in particular. In PhHV-1-infected Crandell feline kidney cells gB is expressed as a 113-kDa glycosylated molecule which is proteolytically cleaved into at least two fragments of 67 and 53-59 kDa apparently forming disulfide-linked heterodimers of 140 kDa. Cell surface expression of PhHV-1 gB was confirmed by FACS analysis. Thus, synthesis and processing of the gB protein of PhHV-1 follows a pattern also observed in other Varicelloviruses. Since the gB protein of herpesviruses, expressed in the baculovirus system, has been shown to be a suitable target for vaccine design, we used this system for expression of PhHV-1 gB. Recombinant (rec) baculovirus-expressed gB was identified as a 105-kDa glycosylated molecule. Proteolytic cleavage into fragments of 62 and 52 kDa was markedly delayed compared to wild-type (wt) gB. Wt and rec gB harbored endoglycosidase H (precursor)- as well as N-glycosidase F-sensitive N-glycans (proteolytic fragments). Baculovirus-expressed gB appeared to be antigenically authentic, since it was recognized in radioimmunoprecipitation and immune peroxidase monolayer assays by PhHV-1-neutralizing seal sera and by gB-specific neutralizing murine monoclonal antibodies. Furthermore, PhHV-1-neutralizing antibodies were induced in mice following immunization with baculovirus-expressed gB, indicating its suitability for incorporation in a candidate vaccine for seals.

Amino Acid Sequence↗

Functional and evolutionary implications of natural variation in clock genes.

Nearly all studies of natural variation within clock genes involve the period (per) locus, which was originally isolated in the fruit-fly. Intra- and interspecific work on per has focused mostly on a region of Thr-Gly or Ser-Gly repeats, which show rapid length and sequence evolution. The functional implications of nucleotide variation in this repetitive array have been characterised using behavioural, molecular, ecological, structural and statistical analyses. A population genetics approach to variation in per has also been useful in defining species histories within Drosophilids and, in some cases, in implicating selective processes in the evolution of the per gene. Interspecific analysis of per expression patterns reveals evolutionary alterations in this clock gene's regulation.

Animals↗

Mouse keratin 19: complete amino acid sequence and gene expression during development.

The complete amino acid sequence of the mouse keratin 19 (K19) was determined from a partial sequence of cDNA isolated from a mouse (day 10.5) embryo library and an amplified genomic fragment. Analysis of the sequence reveals strong evolutionary conservation with other K19s. Examination of the expression of the gene encoding K19 (K19) during development using an RNase protection assay reveals it is expressed in extra-embryonic tissues by day 8.5 and in the embryo proper by at least day 9.5. Furthermore, the K19 gene is induced in differentiating F9 embryonal carcinoma cells. These results indicate that K19 is another keratin, in addition to the K8-K18 pair, which is synthesized early during mouse development. Finally, Southern analysis of the K19 gene reveals that it is found as a unique copy in the mouse genome, in contrast to what is found in humans, which have at least one processed pseudogene.

Amino Acid Sequence↗

Statistical framework for phylogenomic analysis of gene family expression profiles.

Microarray technology has produced massive expression data that are invaluable for investigating the genome-wide evolutionary pattern of gene expression. To this end, phylogenetic expression analysis is highly desirable. On the basis of the Brownian process, we developed a statistical framework (called the E(0) model), assuming the independent expression of evolution between lineages. Several evolutionary mechanisms are integrated to characterize the pattern of expression diversity after gene duplications, including gradual drift and dramatic shift (punctuated equilibrium). When the phylogeny of a gene family is given, we show that the likelihood function follows a multivariate normal distribution; the variance-covariance matrix is determined by the phylogenetic topology and evolutionary parameters. Maximum-likelihood methods for multiple microarray experiments are developed, and likelihood-ratio tests are designed for testing the evolutionary pattern of gene expression. To reconstruct the evolutionary trace of expression diversity after gene (or genome) duplications, we developed a Bayesian-based method and use the posterior mean as predictors. Potential applications in evolutionary genomics are discussed.

Algorithms↗

An attenuated LC16m8 smallpox vaccine: analysis of full-genome sequence and induction of immune protection.

The potential threat of smallpox bioterrorism has made urgent the development of lower-virulence vaccinia virus vaccines. An attenuated LC16m8 (m8) vaccine was developed in 1975 from the Lister strain used in the World Health Organization smallpox eradication program but was not used against endemic smallpox. Today, no vaccines can be tested with variola virus for efficacy in humans, and the mechanisms of immune protection against the major intracellular mature virion (IMV) and minor extracellular enveloped virion (EEV) populations of poxviruses are poorly understood. Here, we determined the full-genome sequences of the m8, parental LC16mO (mO), and grandparental Lister (LO) strains and analyzed their evolutionary relationships. Sequence data and PCR analysis indicated that m8 was a progeny of LO and that m8 preserved almost all of the open reading frames of vaccinia virus except for the disrupted EEV envelope gene B5R. In accordance with this genomic background, m8 induced 100% protection against a highly pathogenic vaccinia WR virus in mice by a single vaccination, despite the lack of anti-B5R and anti-EEV antibodies. The immunogenicity and priming efficacy with the m8 vaccine consisting mainly of IMV were as high as those with the intact-EEV parental mO and grandparental LO vaccines. Thus, mice vaccinated with 10(7) PFU of m8 produced low levels of anti-B5R antibodies after WR challenge, probably because of quick clearance of B5R-expressing WR EEV by strong immunity induced by the vaccination. These results suggest that priming with m8 IMV provides efficient protection despite undetectable levels of immunity against EEV.

Amino Acid Sequence↗

Evolutionary constraints in the mechanism of flavin catalysis.

Analysis of the possible evolution of flavin catalysis in succinate dehydrogenase suggests as the ultimate state an active site that bears one or more acid functions and uses the enediol form of the substrate rather than the carbanion as a nucleophile. In the case of flavoenzyme catalyzed oxidation of fatty acylCoA, alpha-amino acids and alpha-hydroxy acids evolution to a similar mechanism seems to be blocked.

Acyl Coenzyme A↗

Studies on the evolutionary relationships between hemoglobins in Chironomus pallidivittatus and C. tentsans. I. Isolation and immunological analysis of monomeric and dimeric hemoglobins.

The monomeric hemoglobins of Chironomus tentans and C. pallidivittatus have been isolated and separated into their respective components by gel chromatography on Sephadex G-75 and ion-exchange chromatography on DEAE-Sephacel. The amino acid compositions of the purified components are given. The sequence of the 30 N-terminal amino acid residues of one of the monomeric components (Hb I from C. pallidivittatus) was determined and found to be identical in almost all of its parts with the monomeric hemoglobins of C. thummi (CTT III and CTT IV). Antibodies against the monomeric hemoglobins Hb I and Hb IIc and the dimeric fraction were highly specific and no cross reaction between dimeric and monomeric hemoglobins could be demonstrated. The antibodies against the monomers crossreact with the monomeric hemoglobins CTT III and CTT IV of C. thummi. Taken together with genetic data, the immunological results indicate that divergence of monomeric from dimeric forms was an early event in the evolution of the various hemoglobins in Chironomus.

Amino Acid Sequence↗

Phylogenetic analysis of Pseudomonas syringae pathovars suggests the horizontal gene transfer of argK and the evolutionary stability of hrp gene cluster.

Pseudomonas syringae are differentiated into approximately 50 pathovars with different plant pathogenicities and host specificities. To understand its pathogenicity differentiation and the evolutionary mechanisms of pathogenicity-related genes, phylogenetic analyses were conducted using 56 strains belonging to 19 pathovars. gyrB and rpoD were adopted as the index genes to determine the course of bacterial genome evolution, and hrpL and hrpS were selected as the representatives of the pathogenicity-related genes located on the genome (chromosome). Based on these data, NJ, MP, and ML phylogenetic trees were constructed, and thus 3 trees for each gene and 12 gene trees in total were obtained, all of which showed three distinct monophyletic groups: Groups 1, 2 and 3. The observation that the same set of OTUs constitute each group in all four genes suggests that these genes had not experienced any intergroup horizontal gene transfer within P. syringae but have been stable on and evolved along with the P. syringae genome. These four index genes were then compared with another pathogenicity-related gene, argK (the phaseolotoxin-resistant ornithine carbamoyltransferase gene, which exists within the argK-tox gene cluster). All 13 strains of pv. phaseolicola and pv. actinidiae used had been confirmed to produce phaseolotoxin and to have argK, whose sequences were completely identical, without a single synonymous substitution among the strains used (Sawada et al. 1997a). On the other hand, argK were not present on the genomes of the other 43 strains used other than pv. actinidiae and pv. phaseolicola. Thus, the productivity of phaseolotoxin and the possession of the argK gene were shown at only two points on the phylogenetic tree: Group 1 (pv. actinidiae) and Group 3 (pv. phaseolicola). A t test between these two pathovars for the synonymous distances of argK and the tandemly combined sequence of the four index genes showed a high significance, suggesting that the argK gene (or argK-tox gene cluster) experienced horizontal gene transfer and expanded its distribution over two pathovars after the pathovars had separated, thus showing a base substitution pattern extremely different from that of the noncluster region of the genome.

Bacterial Proteins↗

Analysis of a Schnute postulate-based unified growth model for model selection in evolutionary computations.

In order to evaluate the feasibility of a combined evolutionary algorithm-information theoretic approach to select the best model from a set of candidate invasive species models in ecology, and/or to evolve the most parsimonious model from a suite of competing models by comparing their relative performance, it is prudent to use a unified model that covers a myriad of situations. Using Schnute's postulates as a starting point [Schnute, J., 1981. A versatile growth model with statistically stable parameters, Can. J. Fish Aquat. Sci. 38, 1128-1140], we present a single, unified model for growth that can be successfully utilized for model selection in evolutionary computations. Depending on the parameter settings, the unified equation can describe several growth mechanisms. Such a generalized model mechanism, which encompasses a suite of competing models, can be successfully implemented in evolutionary computational algorithms to evolve the most parsimonious model that best fits ground truth data. We have done exactly this by testing the effectiveness of our reaction-diffusion-advection (RDA) model in an evolutionary computation model selection algorithm. The algorithm was validated (with success) against field data sets of the Zebra mussel invasion of Lake Champlain in the United States.

Algorithms↗