Integrins during evolution: Evolutionary trees and model organisms

The integrins form a large family of cell adhesion receptors. All multicellular animals express integrins, indicating that the family evolved relatively early in the history of metazoans, and homologous sequences of the component domains of integrin α and β subunits are seen in prokaryotes. Some integrins, however, seem to be much younger. For example, the αI domain containing integrins, including collagen receptors and leukocyte integrins, have been found in chordates only. Here, we will discuss what conclusions can be drawn about integrin function by studying the evolutionary conservation of integrins. We will also look at how studying integrins in organisms such as the fruit fly and mouse has helped our understanding of integrin evolution-function relationships. As an illustration of this, we will summarize the current understanding of integrin involvement in skeletal muscle formation.     

The glycomes of Caenorhabditis elegans and other model organisms

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fuc alpha 1-2 Gal 1-2 Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.     

BioNetBuilder2.0: bringing systems biology to chicken and other model organisms

Background

Systems Biology research tools, such as Cytoscape, have greatly extended the reach of genomic research. By providing platforms to integrate data with molecular interaction networks, researchers can more rapidly begin interpretation of large data sets collected for a system of interest. BioNetBuilder is an open-source client-server Cytoscape plugin that automatically integrates molecular interactions from all major public interaction databases and serves them directly to the user's Cytoscape environment. Until recently however, chicken and other eukaryotic model systems had little interaction data available.

Results

Version 2.0 of BioNetBuilder includes a redesigned synonyms resolution engine that enables transfer and integration of interactions across species; this engine translates between alternate gene names as well as between orthologs in multiple species. Additionally, BioNetBuilder is now implemented to be part of the Gaggle, thereby allowing seamless communication of interaction data to any software implementing the widely used Gaggle software. Using BioNetBuilder, we constructed a chicken interactome possessing 72,000 interactions among 8,140 genes directly in the Cytoscape environment. In this paper, we present a tutorial on how to do so and analysis of a specific use case.

Conclusion

BioNetBuilder 2.0 provides numerous user-friendly systems biology tools that were otherwise inaccessible to researchers in chicken genomics, as well as other model systems. We provide a detailed tutorial spanning all required steps in the analysis. BioNetBuilder 2.0, the tools for maintaining its data bases, standard operating procedures for creating local copies of its back-end data bases, as well as all of the Gaggle and Cytoscape codes required, are open-source and freely available at http://err.bio.nyu.edu/cytoscape/bionetbuilder/.

     

Shared forces of sex chromosome evolution in haploid-mating and diploid-mating organisms: Microbotryum violaceum and other model organisms

It is usually posited that the most important factors contributing to sex chromosome evolution in diploids are the suppression of meiotic recombination and the asymmetry that results from one chromosome (the Y) being permanently heterozygous and the other (the X) being homozygous in half of the individuals involved in mating. To distinguish between the roles of these two factors, it would be valuable to compare sex chromosomes in diploid-mating organisms and organisms where mating compatibility is determined in the haploid stage. In this latter group, no such asymmetry occurs because the sex chromosomes are equally heterozygous. Here we show in the fungus Microbotryum violaceum that the chromosomes carrying the mating-type locus, and thus determining haploid-mating compatibility, are rich in transposable elements, dimorphic in size, and carry unequal densities of functional genes. Through analysis of available complete genomes, we also show that M. violaceum is, remarkably, more similar to humans and mice than to yeast, nematodes, or fruit flies with regard to the differential accumulation of transposable elements in the chromosomes determining mating compatibility vs. the autosomes. We conclude that restricted recombination, rather than asymmetrical sheltering, hemizygosity, or dosage compensation, is sufficient to account for the common sex chromosome characteristics.     

Man and other introduced organisms

Man's tremendously increased migratory potention, coupled with his ability to transport any material, causes ecological revolutions on most islands of this world–Fernandina and most smaller islands of the Galapagos being fortunate exceptions to that rule. It is proposed to make distinctions between species colonizing the Galapagos We can distinguish between those immigrant species which do not profit from man as a transport medium (independent immigrants) and those who do depend on him (man-dependent immigrants). These immigrants, in turn, may or may not be able to settle and these settlers may either gain a footing with or without depending on man's direct or indirect influence on the habitat (non-settlers, primary resource-using settlers, and secondary resource-using settlers). Introduced species represent a terrible attack on the biotic uniqueness of the Galapagos ecosystems. However, it is proposed to make better use of the scientific value of these introductions. For example, a case of selective impact of an introduced on an indigenous species was investigated: lava lizards of the genus Tropidurus seem to be more wary of moving objects on islands where cats have been introduced by man than on islands free of cats.
Under the peculiar Galapagos conditions it may turn out that science's most difficult and important task is to investigate and interpret man's role in such places.     

From gene to phenotype in Drosophila and other organisms

The growing number of cloned eukaryotic genes lacking a defined or proven biological function poses a major challenge in 'reverse genetics'. A method is described here that permits efficient screening for new lesions in, or close to, genes corresponding to cloned DNA sequences of interest. The technique involves transposon mutagenesis, followed by screening of DNA isolated from a population of mutagenised individuals (or their progeny) for evidence that the population contains at least one individual in which transposon insertion has occurred at the target locus. Detection of rare individuals within the population is facilitated by the use of the polymerase chain reaction (PCR). Once recognised, specific individuals (or their progeny) are isolated from the population by a process of sib-selection. In cases where insertion of the transposon has occurred close to, but not within, the target locus, secondary events involving imprecise excision of the transposon will nonetheless allow the isolation of mutant individuals. Though the method was developed specifically for the transposon-mutagenesis of Drosophila, extensions to other organisms and to other mutagenic strategies are feasible and some of the possibilities are discussed.     

Leader of the pack: gene mapping in dogs and other model organisms

The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. We share many diseases with our canine companions, including cancer, diabetes and epilepsy, making the dog an ideal model organism for comparative disease genetics. Using newly developed resources, whole-genome association in dog breeds is proving to be exceptionally powerful. Here, we review the different trait-mapping strategies, some key biological findings emerging from recent studies and the implications for human health. We also discuss the development of similar resources for other vertebrate organisms.     

Flavonoid function and activity to plants and other organisms.

Flavonoid compounds distribute widely in vascular plants and Bryophytes, and ca. 5,000 kinds have been reported as naturally occurring substances. Many biological activities of the flavonoids were found until now. They include pollinator attractants, oviposition stimulants, feeding attractants and deterrents, allelopathy and phytoalexins. This paper reviews function and activity of flavonoids against plants and other organisms.     

A unified model for apical caspase activation

Apoptosis is orchestrated by the concerted action of caspases, activated in a minimal two-step proteolytic cascade. Existing data suggests that apical caspases are activated by adaptor-mediated clustering of inactive zymogens. However, the mechanism by which apical caspases achieve catalytic competence in their recruitment/activation complexes remains unresolved. We explain that proximity-induced activation of apical caspases is attributable to dimerization. Internal proteolysis does not activate these apical caspases but is a secondary event resulting in partial stabilization of activated dimers. Activation of caspases-8 and -9 occurs by dimerization that is fully recapitulated in vitro by kosmotropes, salts with the ability to stabilize the structure of proteins. Further, single amino acid substitutions at the dimer interface abrogate the activity of caspases-8 and -9 introduced into recipient mammalian cells. We propose a unified caspase activation hypothesis whereby apical caspases are activated by dimerization of monomeric zymogens.     

A host-host-pathogen model with free-living infective stages, applicable to microbial pest control

A model has been investigated of the dynamics of the interaction between two hosts which are both attacked by a common pathogen, where the pathogen has free-living infective stages the population size of which must itself be modelled explicitly, and where the host species do not interact with one another except through their shared pathogen. If either host interacted with the pathogen alone, three broad classes of dynamics would be possible: host regulation, pathogen persistence and pathogen extinction. Here, all possible types of combinations of hosts are examined: regulation-regulation (both hosts would be regulated if they interacted with the pathogen alone), regulation-persistence, regulation-extinction, persistence-persistence persistence-extinction and extinction-extinction. A wide range of dynamics is generated, including a number of patterns quite unlike those found in the one-host pathogen case (e.g. persistence in one host, elimination of the other host) and behaviour contingent on initial densities in the system. For clarity and pertinence, attention is focused on the case where one host is a pest, the pathogen is a potential microbial control agent, and the other host is a non-target species which it is undesirable to harm. The model suggests, broadly, that non-targets are unlikely to be seriously threatened in such cases, and also that non-targets, far from undermining pest control, are quite likely to contribute to its efficacy.     

A taxonomic distance applicable to paleontology

A general Hausdorff-like metric on sets is presented with applications to paleontological “dissimilarity measures.” The distances between taxa represented by living organisms and/or fossil material are obtainable simply and independently of the nature of the characteristics used to define the taxonomic units. In particular, linear independence of the measured anatomical characters is not required.     

A unified model for budburst of trees

Accurate plant phenology (seasonal plant activity driven by environmental factors) models are vital tools for ecosystem simulation models and for predicting the response of ecosystems to climate change. Since the early 1970s, efforts have concentrated on predicting phenology of the temperate and boreal forests because they represent one-third of the carbon captured in plant ecosystems and they are the principal ecosystems with seasonal patterns of growth on Earth (one-fifth of the plant ecosystems area). Numerous phenological models have been developed to predict the growth timing of temperate or boreal trees. They are in general empirical, nonlinear and non-nested. For these reasons they are particularly difficult to fit, to test and to compare with each other. The methodological difficulties as well as the diversity of models used have greatly slowed down their improvement. The aim of this study was to show that the most widely used models simulating vegetative or reproductive phenology of trees are particular cases of a more general model. This unified model has three main advantages. First, it allows for a direct estimation of (i) the response of bud growth to either chilling or forcing temperatures and (ii) the periods when these temperatures affect the bud growth. Second, it can be simplified according to standard statistical tests for any particular species. Third, it provides a standardized framework for phenological models, which is essential for comparative studies as well as for robust model identification.     

A model for suppression and dominance in trees

A new differential equation model for the growth of trees, involving structure/storage partitioning, is set up. The model, which is relatively simple, is shown to exhibit suppression and dominance effects. It also suggests a possible mechanism for the bimodal distributions of tree size which are observed in even-aged monoculture stands.     

A spatial model for the spread of invading organisms subject to competition

 A spatially explicit integrodifference equation model is studied for the spread of an invading organism against an established competitor. Provided the invader is initially confined to a bounded region, the invasion spreads asymptotically as a travelling wave whose speed depends on the strength of the competitive interaction and on the dispersal characteristics of the invader. Even an inferior, but established, competitor can significantly reduce the invasion speed. The invasion speed is also influenced by the exact shape of the dispersal kernel (especially the thickness of the tail) as well as the mean dispersal distance for each generation. Received 10 April 1996; received in revised form 21 August 1996