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Results for “evolutionarily stable strategy”

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PubMed2006

Towards the creation of novel proteins by block shuffling.

We have been investigating the creation of novel proteins by means of block shuffling, where the term block refers to an amino acid sequence that corresponds to particular features of proteins, such as secondary structures, modules, functional motifs, and so on. Block shuffling makes it possible to explore the global sequence space, which is not feasible with conventional methods, such as DNA shuffling or family shuffling. To investigate what properties are required for the building blocks, we have analyzed the foldability and enzymatic activity of barnase mutants obtained by permutation of modules or secondary structure units. This reconstructive approach indicated that secondary structure units with mutual long-range interactions are more suitable than modules as building blocks, at least in the case of barnase. The results also suggested that proteins in evolutionarily intermediate states are created by block shuffling, and such proteins have the potential to be evolved into mature globular proteins. For the construction of combinatorial protein libraries, we have developed random multi-recombinant PCR (RM-PCR), which can combine different DNA fragments without homologous sequences. The libraries can be utilized for in vitro selection using in vitro virus (mRNA display) or stable (DNA display), which have also been developed in our laboratory. In this review article, we summarize our strategy to create novel proteins by block shuffling and review key literature in the field. Possible applications of the block shuffling strategy are also discussed.

Combinatorial Chemistry Techniques↗

PubMed2006

Evolutionary regime shifts in age and size at maturation of exploited fish stocks.

Worldwide declines of fish stocks raise concerns about deleterious consequences of harvesting for stock abundances and individual life histories, and call for appropriate recovery strategies. Fishes in exploited stocks mature earlier at either larger or smaller sizes due to both genetic and plastic responses. The latter occur commonly when reduced competition for food leads to faster growth. Using a size-structured consumer-resource model, which accounts for both genetic and plastic responses, we show that fisheries-induced evolutionary changes in individual life history and stock properties can easily become irreversible. As a result of annual spawning, early maturation at small sizes and late maturation at large sizes can become alternative, evolutionarily and ecologically stable states under otherwise identical environmental conditions. Exploitation of late-maturing populations can then induce an evolutionary regime shift to smaller maturation sizes associated with stepwise, 1-year decreases in age at first reproduction. Complete and early fishing moratoria slowly reverse this process, but belated or partial closure of fisheries may accelerate or even instigate further evolution to smaller sizes at maturation. We suggest that stepwise decreases in maturation age can be used as early warnings of upcoming evolutionary changes, and should inspire timely restrictions of fisheries.

Adaptation, Physiological↗

PubMed2005

Generation and characterization of a panel of monoclonal antibodies specific for human fibroblast growth factor receptor 4 (FGFR4).

Fibroblast growth factor receptor 4 (FGFR4) is a member of the FGFR family of receptor tyrosine kinases, and plays important roles in a variety of biological functions such as cell proliferation, differentiation, migration, angiogenesis, tissue repair, and tumorigenesis. The human FGFRs share a high degree of sequence homology between themselves, as well as with their murine homologs. Consequently, it has been suggested that it may be difficult to prepare monoclonal antibodies (MAbs) that are specific for the individual receptor types. In this communication, we report on the development and characterization of a panel of anti-human FGFR4 MAbs that were generated in mice using a rapid immunization protocol. Using a modified rapid immunization at multiple sites (RIMMS) protocol with the soluble extracellular domain of human FGFR4 (FGFR4-ECD), the immunized mice developed high levels of polyclonal IgG to the immunogen within 13 days of the first immunization. The lymph node cells isolated from the immunized animals were then fused with mouse myeloma cells for hybridoma generation. Use of an efficient hybridoma cloning protocol in combination with an ELISA screening procedure allowed for early identification of stable hybridomas secreting antihuman FGFR4 IgG. Several identified MAbs specifically reacted with the FGFR4 protein without binding to the other human isoforms (FGFR1, FGFR2, and FGFR3). As evaluated by BIAcore analysis, most anti-FGFR4 MAbs displayed high affinities (8.6 x 10(8) approximately 3.9 x 10(10) M) to FGFR4. Furthermore, these MAbs were able to bind to FGFR4 expressed on human breast tumor cell lines MDA-MB-361 and MDA-MB-453. Taken together, the results demonstrate that the RIMMS strategy is an effective approach for generating class-switched, high-affinity MAbs in mice to evolutionarily conserved proteins such as human FGFR4. These MAbs may be useful tools for further investigation of the biological functions and pathological roles of human FGFR4.

Animals↗

PubMed2004

Avoiding synchrony as a strategy of female mate choice.

It has long been thought that some female mammals (e.g., humans and Norway rats) synchronize their ovarian cycles when in close proximity. However, re-analyses of these studies have revealed serious and systematic methodological errors. In retrospect, this is exactly what should have been expected given that female mammals exhibit considerable ovarian cycle-length variability, which prevents synchrony. Despite the diversity of cycle lengths in mammals, little attention has been paid to possible adaptive functions of cycle-length in female mate choice. Thus an individual-based model of Norway rats is described here that uses actual data from an experimentally constructed habitat. Results showed that synchrony is costly to females in achieving matings with high quality males because synchrony forces female-female competition. Synchrony can be avoided by evolving longer cycles, but there are limits on cycle length due to the cost of waiting. Furthermore, it is possible for inter- and intra-female cycle length variability to be evolutionarily stable within a population; thus offering a plausible explanation for some of the diversity observed in ovarian cycle lengths in female mammals.

Adaptation, Physiological↗

PubMed1993

Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences.

Despite the rapid mutational change that is typical of positive-strand RNA viruses, enzymes mediating the replication and expression of virus genomes contain arrays of conserved sequence motifs. Proteins with such motifs include RNA-dependent RNA polymerase, putative RNA helicase, chymotrypsin-like and papain-like proteases, and methyltransferases. The genes for these proteins form partially conserved modules in large subsets of viruses. A concept of the virus genome as a relatively evolutionarily stable "core" of housekeeping genes accompanied by a much more flexible "shell" consisting mostly of genes coding for virion components and various accessory proteins is discussed. Shuffling of the "shell" genes including genome reorganization and recombination between remote groups of viruses is considered to be one of the major factors of virus evolution. Multiple alignments for the conserved viral proteins were constructed and used to generate the respective phylogenetic trees. Based primarily on the tentative phylogeny for the RNA-dependent RNA polymerase, which is the only universally conserved protein of positive-strand RNA viruses, three large classes of viruses, each consisting of distinct smaller divisions, were delineated. A strong correlation was observed between this grouping and the tentative phylogenies for the other conserved proteins as well as the arrangement of genes encoding these proteins in the virus genome. A comparable correlation with the polymerase phylogeny was not found for genes encoding virion components or for genome expression strategies. It is surmised that several types of arrangement of the "shell" genes as well as basic mechanisms of expression could have evolved independently in different evolutionary lineages. The grouping revealed by phylogenetic analysis may provide the basis for revision of virus classification, and phylogenetic taxonomy of positive-strand RNA viruses is outlined. Some of the phylogenetically derived divisions of positive-strand RNA viruses also include double-stranded RNA viruses, indicating that in certain cases the type of genome nucleic acid may not be a reliable taxonomic criterion for viruses. Hypothetical evolutionary scenarios for positive-strand RNA viruses are proposed. It is hypothesized that all positive-strand RNA viruses and some related double-stranded RNA viruses could have evolved from a common ancestor virus that contained genes for RNA-dependent RNA polymerase, a chymotrypsin-related protease that also functioned as the capsid protein, and possibly an RNA helicase.

Amino Acid Sequence↗

PubMed1999

Evolution of stepping-stone dispersal rates.

We present a general model of the evolution of dispersal in a population with any distribution of dispersal distance. We use this model to analyse evolutionarily stable (ES) dispersal rates for the classical island model of dispersal and for three different stepping-stone models. Using general techniques to compute relatedness coefficients in the different dispersal models which we consider, we find that the distribution of dispersal distance may affect the ES dispersal rate when the cost of dispersal is low. In this case the ES dispersal rate increases with the number of demes that can be reached by one dispersal event. However, for increasing cost the ES dispersal rate converges to a value independent of the distribution of dispersal distance. These results are in contrast to previous analyses of similar models. The effects of the size (number of demes) and shape (ratio between the width and the length) of the population on the evolution of dispersal are also studied. We find that larger and more elongated populations lead generally to higher ES dispersal rates. However, both of these effects can only be observed for extreme parameter values (i.e. for very small and very elongated populations). The direct fitness method and the analytical techniques used here to compute relatedness coefficients provide an efficient way to analyse ES strategies in subdivided populations.

Animals↗

PubMed2026

ECLIPSE: exploring the dark proteome of ESKAPE pathogens through the sequence similarity network of the Protein Universe Atlas.

MOTIVATION: The accelerating crisis of antimicrobial resistance among the critical so-called ESKAPE pathogens demands the urgent identification of novel molecular targets. However, a substantial fraction of ESKAPE proteomes remains functionally uncharacterized, with many genes annotated as encoding hypothetical proteins. These protein sequences often lack significant similarity to known protein families when conventional homology-based annotation methods are used and thus remain "dark". This limits our ability to explore their roles in pathogenicity, and it is thus crucial to bridge this substantial gap in pathogen biology by developing new strategies to illuminate these "dark" regions of the ESKAPE pan-proteome. RESULTS: We introduce ECLIPSE (ESKAPE Connectome Linkage and Inference for Proteome Sequence Exploration), a network-based computational framework that systematically identifies and prioritizes functionally dark protein families in ESKAPE pan-proteomes. ECLIPSE embeds target ESKAPE pathogen proteomes within the global sequence similarity network of the Protein Universe Atlas. It detects connected components composed entirely of unannotated proteins, called the "dark proteome." As a case study, we applied ECLIPSE to a pan-proteome of 3 460 657 protein sequences from 635 strains of Pseudomonas aeruginosa (PA). ECLIPSE identified 120 985 proteins (4%) residing in completely dark connected components. Furthermore, we have performed a taxonomic diversity analysis using normalized Shannon indices to characterize each dark component by its enrichment in ESKAPE pathogens. The analysis utilized the evenness (E) value (see Methods 2.1), which distinguishes Pseudomonas-specific (target-specific) from ESKAPE-enriched dark components. We then developed the Dark Proteome Prioritization Score (DPPS), a composite multidimensional scoring framework (see Methods 2.5). It ranks these dark components by biological relevance across four orthogonal axes: (i) functional darkness, (ii) P. aeruginosa proportion in the Atlas, (iii) AMR-clade taxonomic restriction, and (iv) conservation across the 635 P. aeruginosa strains. This framework outputs a robust four-tier scoring system; the prioritized Tier I components were validated by weight sensitivity analysis and remained stable across 500 Monte Carlo weight perturbations. Structural characterization of one of the top-ranked ESKAPE-enriched dark components revealed that it belongs to the beta-barrel fold DUF1302 (PF06980) family, for which no experimentally solved three-dimensional structure exists in the PDB. The genomic context analysis indicates that it is co-localized with a LuxR-type transcriptional regulator. Collectively, ECLIPSE identifies evolutionarily conserved, structurally defined, and functionally dark proteins enriched across ESKAPE pathogens; these dark proteins can further be utilized as alternative antimicrobial targets for experimental characterization. AVAILABILITY AND IMPLEMENTATION: The source code and dataset are available for free at: Github: https://github.com/surabhilata/ECLIPSE.git, Zenodo: DOI: 10.5281/zenodo.21064323.

Proteome↗