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Cytolethal distending toxin: limited damage as a strategy to modulate cellular functions.

The coevolution of bacterial pathogens and their hosts has contributed to the development of very complex and sophisticated functional pathogen--host interfaces. Thus, well-adapted pathogens have evolved a variety of strategies to manipulate host cell functions precisely. For example, a group of unrelated Gram-negative pathogenic bacteria have evolved a toxin, known as cytolethal distending toxin (CDT), that has the ability to control cell cycle progression in eukaryotic cells. Recent studies have identified CdtB as the active subunit of the CDT holotoxin. Through its nuclease activity, CdtB causes limited DNA damage, thereby triggering the DNA-damage response that ultimately results in the observed arrest of the cell cycle. In addition, it has been established that CDT is a tripartite AB toxin in which CdtB is the active 'A' subunit and CdtA and CdtC constitute the heterodimeric 'B' subunit required for the delivery of CdtB into the target cell. The mechanism of action of CDT suggests that the infliction of limited damage could be a strategy used by pathogenic bacteria to modulate host cell functions.

Amino Acid Sequence↗

Leech mycetome endosymbionts are a new lineage of alphaproteobacteria related to the Rhizobiaceae.

Mycetomal organs attached to the esophagus of hematophagous leeches which are known to harbor endosymbiotic bacteria were removed from three species in the leech family Glossiphoniidae. Anatomical observations indicated that placobdellid mycetomes are paired and caecate, inserting into the esophagus posterior to the proboscis. Light and electron microscopy demonstrated that there is a single layer of mycetome epithelial cells harboring gram-negative rods and that these epithelial cells are ultrastructurally distinct from neighboring esophageal epithelial cells. Fluorescent in situ hybridization with eubacterial and alphaproteobacterial probes localized the bacteria solely to the mycetomes both in adult and in unfed juvenile leeches whereas a gammaproteobacterial probe did not yield a bound fluorescencent signal. DNA was isolated from these tissues and subjected to PCR amplification using bacteria-specific primers for 16S and 23S rDNA. Results from sequencing the amplification products and phylogenetic analysis with other Alphaproteobacteria revealed that the bacteria resident in these organs comprise a new genus of Alphaproteobacteria, Reichenowia n. gen., closely related to the nitrogen-fixing, nodule-forming Rhizobiaceae. The three bacterial strains, though different from each other were each other's closest relatives, suggesting a history of close coevolution with their leech hosts.

Alphaproteobacteria↗

A molecular predator and its prey: coupled isothermal amplification of nucleic acids.

BACKGROUND: A novel approach to the study of in vitro evolution is provided by the investigation of continuous, functionally coupled, amplifying systems. To date, in vitro evolution experiments have focused on issues of mutation and selection. Our work contributes to the new field of in vitro molecular ecology studies in which detailed information about the relationship between sequence changes and molecular interactions is obtained. Predator-prey systems are interesting in this context both in terms of evolutionary limits and in terms of the potential kinetic properties of oscillation and spatial pattern formation. Such molecular predator-prey models can be extended to a further negative-interaction mode, viral-host molecular evolution. RESULTS: A simple, nonfunctional predator-prey system based on the self-sustained sequence replication reaction is proposed. Coupling within the system is achieved using the single-stranded DNA intermediate of one cycle, the prey cycle, as primer for the second one, the predator cycle. Hybridization by complementary base pairing is the second order reaction step underlying the predation. Single steps of the whole reaction system have been investigated by radiolabeling. Each isolated subsystem operates according to the proposed reaction scheme, and evidence for an efficient coupling of both subsystems according to the proposed mechanism was found. CONCLUSIONS: Simple, interacting model systems based on nucleic acids can be designed and constructed for the study of coevolution. The results of studies such as the one described here will provide a basis for the construction of coupled systems of ribozymes, from which point the engineering of catalytic units for applications in biotechnology is feasible.

Base Sequence↗

Microsporidian life cycles and diversity: the relationship between virulence and transmission.

The microsporidia are obligate intracellular parasites which have diverse life cycles involving both horizontal and vertical transmission and parasitise a wide range of vertebrate and invertebrate hosts. In this paper we consider the life cycles and diversity of the microsporidia. We focus in particular on the relationship between parasite transmission and virulence and its implications for host-parasite coevolution. The use of horizontal and vertical routes of transmission varies between species and there is a strong link between transmission and virulence. Horizontal transmission is characterised by a high parasite burden and associated pathogenicity. In contrast, vertical transmission is characterised by low virulence, which has led to under-reporting of this important transmission route. Vertically transmitted microsporidia may also cause male killing or feminisation of their host, with implications for host population sex ratio and stability. Phylogenetic analysis shows that vertical transmission occurs in diverse branches of the Microspora. We find that there is evidence for vertical transmission in both vertebrate and invertebrate hosts and conclude that it is a common or possibly even ubiquitous transmission route within this phylum.

Animals↗

Plant-pathogen arms races at the molecular level.

Advances in research into the genetics of plant-pathogen interactions include an embracing of evolutionary ideas and methodologies. Recent studies reveal positive selection and selective maintenance of variation in plant resistance and defense-related genes. Coevolution between plants and their enemies involves many interactions at the molecular level.

Animals↗

Origin and evolution of Schistosoma japonicum.

In his hypothesis on the coevolution of Asian schistosomes and snails, Davis implies that the ancestors of the Schistosoma japonicum and S. indicum species group were African and arrived in Asia via the Indian plate. This paper briefly reviews molecular phylogenetic relationships among species of the genus Schistosoma to test Davis' theory about the origin and evolution of S. japonicum. All analyses using DNA base sequences, mitochondrial genome gene order and C-banding patterns suggest that Schistosoma originated in Asia and not Africa.

Africa↗

Glia maturation factor gamma (GMFG): a cytokine-responsive protein during hematopoietic lineage development and its functional genomics analysis.

Human hematopoiesis was evaluated using the techniques of controlled stem cell differentiation, two-dimensional gel electrophoresis-based proteomics, and functional genomics. We provide the first report that glia maturation factor gamma (GMFG) is a cytokine-responsive protein in erythropoietin-induced and granulocyte-colony stimulating factor-induced hematopoietic lineage development. Results from global functional genomics analysis indicate that GMFG possesses several other features: hematopoietic tissue-specific gene expression, a promoter concentrated with high-score hematopoiesis-specific transcription factors, and possible molecular coevolution with a rudimentary blood/immune system. On the basis of our findings, we hypothesize that GMFG is a hematopoietic-specific protein that may mediate the pluripotentiality and lineage commitment of human hematopoietic stem cells.

Amino Acid Sequence↗

The relationship between the rate of transposition and transposable element copy number for copia and Doc retrotransposons of Drosophila melanogaster.

We present data on the relationship between the rate of transposition and copy number in the genome for the copia and Doc retrotransposons of Drosophila melanogaster. copia and Doc transposition rates were directly measured in sublines of the isogenic 2b line using individual males or females, respectively, with a range of copia copy numbers from 49 to 103 and Doc copy numbers from 112 to 235 per genome. Transposition rates varied from 3 x 10(-4) to 2 x 10(-2) for copia and from 2 x 10(-4) to 2 x 10(-3) for Doc. A positive relationship between transposition rate and copy number was found both for copia and for Doc when the data were analysed across all the 2b individuals; no significant correlation was found when the data were analysed across the subline means for both retrotransposons tested. Overall, correlation between copia and Doc transposition rate and their copy number in the genome, if any, was not negative, which would be expected if transposable elements (TEs) self-regulate their copy number. Thus, for copia and Doc no evidence for self-regulation was provided, and at least for these two TEs this hypothesis is not favoured for explaining the maintenance of the stable copy number that is characteristic for natural populations. The transposition rate of copia was measured twice, and a strong positive correlation between copy number and transposition rate both across individuals and subline means was found in 1994, while in 1995 no correlation was found. This fact is in agreement with the hypothesis that a positive correlation between the rate of transposition and TE copy number may be a default starting point for future host-TE coevolution.

Animals↗

The effects of mating probability on the population genetics of nematodes.

We review how constraints on the mating probability of female worms by segregation within individual host guts form a critical element in the parasite population structure of nematodes. We consider the effects of these constraints on the population genetics of nematodes under various assumptions regarding worm competition as reflected in the relationship between the abundance of a certain genotype within the gut and the probability of reproductive success. The consequences for the emergence of resistance to drugs and immunotherapy and implications for host-parasite coevolution are discussed. We also review evidence for genetic heterogeneity in parasite populations as a necessary prerequisite for the applicability of mating probability models designed to assess the population genetics of nematodes.

Animals↗

Systematic temporal changes in host susceptibility to infection: demographic mechanisms.

Simple mathematical models are developed to examine the influence of variability in host susceptibility to infection, on the dynamics of host-parasite population interactions. When hosts differ in their innate susceptibility (at birth), to infection by a specific parasite, the average susceptibility of the host population as a whole may show systematic changes through time. Such patterns may arise as a result of demographic factors associated with the interaction between host and parasite populations, in the absence of inheritance mechanisms (a genetic component) or acquired resistance (an immunological component). The general significance of this observation is discussed in terms of the coevolution of host-parasite associations.

Animals↗

Virulence of lizard malaria: the evolutionary ecology of an ancient parasite-host association.

The negative consequences of parasitic infection (virulence) were examined for two lizard malaria parasite-host associations: Plasmodium agamae and P. giganteum, parasites of the rainbow lizard, Agama agama, in Sierra Leone, West Africa; and P. mexicanum in the western fence lizard, Sceloporus occidentalis, in northern California. These malaria species vary greatly in their reproductive characteristics: P. agamae produces only 8 merozoites per schizont, P. giganteum yields over 100, and P. mexicanum an intermediate number. All three parasites appear to have had an ancient association with their host. In fence lizards, infection with malaria is associated with increased numbers of immature erythrocytes, decreased haemoglobin levels, decreased maximal oxygen consumption, and decreased running stamina. Not affected were numbers of erythrocytes, resting metabolic rate, and sprint running speed which is supported by anaerobic means in lizards. Infected male fence lizards had smaller testes, stored less fat in preparation for winter dormancy, were more often socially submissive and, unexpectedly, were more extravagantly coloured on the ventral surface (a sexually dimorphic trait) than non-infected males. Females also stored less fat and produced smaller clutches of eggs, a directly observed reduction in fitness. Infected fence lizards do not develop behavioural fevers. P. mexicanum appears to have broad thermal buffering abilities and thermal tolerance; the parasite's population growth was unaffected by experimental alterations in the lizard's body temperature. The data are less complete for A. agama, but infected lizards suffered similar haematological and physiological effects. Infected animals may be socially submissive because they appear to gather less insect prey, possibly a result of being forced into inferior territories. Infection does not reduce clutch size in rainbow lizards, but may lengthen the time between clutches. These results are compared with predictions emerging from several models of the evolution of parasite virulence. The lack of behavioural fevers in fence lizards may represent a physiological constraint by the lizards in evolving a thermal tolerance large enough to allow elimination of the parasite via fever. Such constraints may be important in determining the outcome of parasite-host coevolution. Some theory predicts low virulence in old parasite-host systems and higher virulence in parasites with greater reproductive output. However, in conflict with this argument, all three malarial species exhibited similar high costs to their hosts.

Animals↗

Selection and evolution of virulence in bacteria: an ecumenical excursion and modest suggestion.

Why do parasites kill their hosts? During this past decade, research in three different areas; evolutionary ecology, medical microbiology, and population genetics has provided theory and data that address this and related questions of selection and the evolution and maintenance of parasite virulence. A general theory of parasite-host coevolution and the conditions for selection to favour parasite virulence has been put forth. Considerable advances have been made in elucidating the mechanisms of pathogenicity and inheritance of virulence in bacteria. The population genetic structure and the relationship between pathogenic and non-pathogenic forms has been determined for a number of species of bacteria. We critically review these developments and their implications for questions of selection and the evolution and maintenance of virulence in bacteria. We postulate how selection may operate on specific types of bacterial virulence and present a general protocol to experimentally test hypotheses concerning selection and the evolution of virulence in bacteria.

Animals↗

Evolutionary relationships between trematodes and snails emphasizing schistosomes and paragonimids.

Snails and digeneans have been associated for at least 200 million years. Their inter-relationships over such a time-span must have been complex and varied. Few studies have attempted to explore these relationships in the light of knowledge of the phylogeny of both host and parasite groups. Here we focus on two important families of digeneans, the Schistosomatidae and the Paragonimidae, for which molecular phylogenies are available. We investigate the types of evolutionary relationships between host and parasite, operating at different phylogenetic depths, that might explain current host specificity and distributions of both associates. Both families of parasites utilise a number of highly diverged gastropod families, indicating that host extensions have featured in their histories. However, schistosomatids and paragonimids show different patterns of association with their snail hosts. As befits the apparently more ancient group, schistosomatids utilise snails from across a wide phylogenetic range within the Gastropoda. The genus Schistosoma itself has experienced one long-range host switch between pulmonates and caenogastropods. By contrast, paragonimids are restricted to two superfamilies of caenogastropods. Despite these differences, modern schistosomatid species appear to be more host specific than are paragonimids and host additions, at the level of host family, are far less common among species of schistosomatids than among paragonimids. Some species of Paragonimus exhibit remarkably low levels of host specificity, with different populations utilising snails of different families. Existing knowledge relating to the phenomenon will be presented in the context of phylogenies of schistosomatids, paragonimids, and their snail hosts. Discussion focuses on the usefulness of current theories of snail-digenean coevolution for interpreting these findings. In the past, much emphasis has been placed on the idea that digeneans engage in a one-to-one arms race with their snail host. We consider that phylogenetic tracking rather than an arms-race relationship might be a common alternative. Not being bound by the restrictions imposed by an arms race, some digeneans might be able to extend to new host species more easily than the literature suggests. Switches into related host taxa are most likely. However, ecologically equivalent but unrelated gastropod hosts may also be exploited. Given the right ecological setting, digeneans are able to switch across considerable phylogenetic distances. Examples from the Paragonimidae and Schistosomatidae are given.

Animals↗

The consequences of self-fertilization and outcrossing of the cestode Schistocephalus solidus in its second intermediate host.

Many hermaphroditic parasites reproduce by both cross-fertilization and self-fertilization. To understand the maintenance of such mixed mating systems it is necessary to compare the fitness consequences of the two reproductive modes. This has, however, almost never been done in the context of host-parasite coevolution. Here we show the consequences of outcrossing and selfing in an advanced life-stage of the cestode Schistocephalus solidus, i.e. in its second intermediate host, the three-spined stickleback (Gasterosteus aculeatus). Each juvenile stickleback was simultaneously exposed to 2 experimentally infected copepods, one harbouring outcrossed the other selfed parasites. At 60 days p.i. parasites were removed from the fish's body cavity and, with microsatellite markers, assigned to either outcrossed or selfed origin. Prevalence was not significantly higher in outcrossed parasites. However, those fish that were infected contained significantly more out-crossed than selfed parasites. Thus the probability of a selfed parasite to progress in the life-cycle is reduced in the second intermediate host. Furthermore, we found that even the multiply infected fish increased in weight during the experiment. Nevertheless, total worm weight in multiply infected fish was significantly lower than in singly infected ones, which thus might be a parasite life-history strategy.

Animals↗

Parasite immune evasion and exploitation: reflections and projections.

Recent developments in parasite immune evasion and exploitation are reviewed with special reference to the papers presented in this volume. Parasites, broadly defined, of animals with good immune responses have evolved many strategies that adapt them to survive and reproduce. These strategies may be passive, or may involve active intervention with host immune regulation, and can be categorized as immune evasion, immune exploitation and molecular piracy. The concept of immune evasion began with Paul Ehrlich's demonstration of antigenic variation in African trypanosomes and was reinforced by later ideas on molecular mimicry. Molecular mimicry is updated in the light of recent discoveries about degeneracy and plasticity of TCR/MHC-peptide recognition. Possible connections between two of its postulated consequences, evasion and autoimmunity, are discussed. Another putative consequence of molecular mimicry, host antigenic polymorphism, is also updated. The concept of exploitation of host immune responses by parasites has been reinforced by new data on its first known examples, especially the immune dependence of schistosome egg excretion. Newer examples include use of host cytokines as parasite growth factors, virokines, viroreceptors and helminth pseudocytokines. Finally, questions of host gene capture by viruses and possible horizontal gene transfer between host and parasite mediated by retroviruses are examined. The latter is compared with molecular conservation as a source of molecular mimicry and other aspects of host--parasite coevolution.

Animals↗

Host-parasite population genetics: a cross-sectional comparison of Bulinus globosus and Schistosoma haematobium.

The genetic population structures of the freshwater snail Bulinus globosus and its trematode parasite Schistosoma haematobium from 8 river sites in the Zimbabwean highveld were compared using randomly amplified DNA (RAPD) markers. There was significant variability between snail populations collected at different sites, but schistosome populations only showed differentiation at a wider geographical scale (between 2 non-connected river systems). For snails, genetic distance was better correlated with proximity along rivers than absolute geographical separation. In contrast, schistosome genetic distance was better correlated with absolute geographical separation than proximity along rivers. These results are consistent with different dispersal mechanisms for snails and schistosomes and the implications for host-parasite coevolution are discussed.

Animals↗

Culture in whales and dolphins.

Studies of animal culture have not normally included a consideration of cetaceans. However, with several long-term field studies now maturing, this situation should change. Animal culture is generally studied by either investigating transmission mechanisms experimentally, or observing patterns of behavioural variation in wild populations that cannot be explained by either genetic or environmental factors. Taking this second, ethnographic, approach, there is good evidence for cultural transmission in several cetacean species. However, only the bottlenose dolphin (Tursiops) has been shown experimentally to possess sophisticated social learning abilities, including vocal and motor imitation; other species have not been studied. There is observational evidence for imitation and teaching in killer whales. For cetaceans and other large, wide-ranging animals, excessive reliance on experimental data for evidence of culture is not productive; we favour the ethnographic approach. The complex and stable vocal and behavioural cultures of sympatric groups of killer whales (Orcinus orca) appear to have no parallel outside humans, and represent an independent evolution of cultural faculties. The wide movements of cetaceans, the greater variability of the marine environment over large temporal scales relative to that on land, and the stable matrilineal social groups of some species are potentially important factors in the evolution of cetacean culture. There have been suggestions of gene-culture coevolution in cetaceans, and culture may be implicated in some unusual behavioural and life-history traits of whales and dolphins. We hope to stimulate discussion and research on culture in these animals.

Animals↗

On the phylogeny of some polyketide synthase genes in the lichenized genus Lecanora.

The ketosynthase domains of putative polyketide synthase (PKS) genes from 15 species in the lichenized genus Lecanora as well as three representatives of other genera were amplified and sequenced using conserved primers. A phylogenetic analysis was carried out with the corresponding amino acid sequences, including those of non-lichenized fungi. The phylogenetic hypothesis places all PKS sequences from Lecanora and the other genera in a clade of PKSs that produce complex aromatic compounds. The PKSs from Lecanora are found in two distinct clades. One of these forms a monophyletic group with PKSs producing precursors of dihydroxy naphthalenes from non-lichenized species. This includes PKSs from the L. rupicola group and several other species which are not closely related. The other clade represents at least one functionally different protein and has no close relationships with known PKSs from other fungi. A comparison between an ITS phylogeny of the species with their DNA sequences of ketosynthase domains reveals similar PKS genes in certain closely related species. Coevolution was unapparent in other clades, suggesting the presence of paralogous genes.

Amino Acid Sequence↗