Mathematical and computational approaches can complement experimental studies of host–pathogen interactions

In addition to traditional and novel experimental approaches to study host–pathogen interactions, mathematical and computer modelling have recently been applied to address open questions in this area. These modelling tools not only offer an additional avenue for exploring disease dynamics at multiple biological scales, but also complement and extend knowledge gained via experimental tools. In this review, we outline four examples where modelling has complemented current experimental techniques in a way that can or has already pushed our knowledge of host–pathogen dynamics forward. Two of the modelling approaches presented go hand in hand with articles in this issue exploring fluorescence resonance energy transfer and two-photon intravital microscopy. Two others explore virtual or ' in silico ' deletion and depletion as well as a new method to understand and guide studies in genetic epidemiology. In each of these examples, the complementary nature of modelling and experiment is discussed. We further note that multi-scale modelling may allow us to integrate information across length (molecular, cellular, tissue, organism, population) and time (e.g. seconds to lifetimes). In sum, when combined, these compatible approaches offer new opportunities for understanding host–pathogen interactions.     

Two-photon microscopy of host–pathogen interactions: acquiring a dynamic picture of infection in vivo

Two-photon (2P) microscopy has become increasingly popular among immunologists for analysing single-cell dynamics in tissues. Researchers are now taking 2P microscopy beyond the study of model antigen systems (e.g. ovalbumin immunization) and are applying the technique to examine infection in vivo . With the appropriate fluorescent probes, 2P imaging can provide high-resolution spatio-temporal information regarding cell behaviour, monitor cell functions and assess various outcomes of infection, such as host cell apoptosis or pathogen proliferation. Imaging of transgenic and knockout mice can be used to probe molecular mechanisms governing the host response to infection. From the microbe side, imaging genetically engineered mutant strains of a pathogen can test the roles of specific virulence factors in pathogenesis. Here, we discuss recent work that has applied 2P microscopy to study models of infection and highlight the tremendous potential that this approach has for investigating host–pathogen interactions.     

Adaptation in an insect host–plant pathogen interaction

Selection on parasites to adapt to local host populations may be direct or through other components of the system such as vectors or the food plant on which the parasite is ingested. To test for local adaptation of nucleopolyhedrovirus among island populations of western tent caterpillars, Malacosoma californicum pluviale, we compared virus isolates from three geographically distinct sites with different dominant host plants. Pathogenicity, speed of kill and virus production of each isolate were examined on the three food plants. Virus isolates from the two permanent host populations had the fastest speed of kill on the host plant from which they were isolated. This was not the case for a caterpillar population that goes extinct when populations are regionally low. Virus isolates on some plant species combined rapid speed of kill with high virus yield. Infection of hosts by mixed microparasite populations could facilitate local adaptation in response to differing food plant chemistry.     

Coevolutionary interactions in a host–parasite system

Interactions between parasitic cuckoos and their hosts represent a classic example of coevolution, where adaptations in the parasite to exploit the host select for defences, which in turn select for new parasite adaptations. Current interactions between the two parties may be at an evolutionary equilibrium or, alternatively, a coevolutionary arms race may be taking place. By taking into account the effect of gene flow in 15 European magpie ( Pica pica ) populations, we studied the coevolutionary interactions with its brood parasite, the great spotted cuckoo ( Clamator glandarius ). Our results suggest that, in Europe, magpies and cuckoos are engaged in an ongoing coevolutionary process because, despite controlling for the large amounts of gene flow among different magpie populations, we still found a positive relationship between host defence (i.e. foreign egg recognition and rejection) and parasite selection pressure.     

Horizontal gene transfer

This review explores examples of horizontal genetic transfer in eukaryotes and prokaryotes. The best understood of these involves various conserved families of transposable elements, but examples of non-transposable-element-based movement of genes or gene clusters have also been identified in prokaryotic genomes. A unifying theme is the structural and DNA-sequence homology of transposable elements from widely unrelated genomes, suggesting evolutionarily conserved mechanisms for horizontal transfer. This is reinforced by the fundamental similarity in the enzymatic mechanisms of retro viral integration (by integrases) and of transposition (by transposases). The review deals with various types of horizontal transfer, the mechanisms available for such transfer, potential barriers, and the evolutionary significance of horizontal genetic transfer.     

Horizontal gene transfer and phylogenetics

The initial analysis of complete genomes has suggested that horizontal gene transfer events are very frequent between microorganisms. This could potentially render the inference, and even the concept itself, of the organismal phylogeny impossible. However, a coherent phylogenetic pattern has recently emerged from an analysis of about a hundred genes, the so-called 'core', strongly suggesting that it is possible to infer the phylogeny of prokaryotes. Also, estimation of the frequency of horizontal gene transfers at the genome level in a phylogenetic context seems to indicate that it is rather low, although of significant biological impact. Nevertheless, it should be emphasized that the history of microorganisms cannot be properly represented by the phylogeny of the core, which represents only a tiny fraction of the genome. This history, even if horizontal gene transfers are rare, should be represented by a network surrounding the core phylogeny.     

Horizontal gene transfer and bacterial diversity

Bacterial genomes are extremely dynamic and mosaic in nature. A substantial amount of genetic information is inserted into or deleted from such genomes through the process of horizontal transfer. Through the introduction of novel physiological traits from distantly related organisms, horizontal gene transfer often causes drastic changes in the ecological and pathogenic character of bacterial species and thereby promotes microbial diversification and speciation. This review discusses how the recent influx of complete chromosomal sequences of various microorganisms has allowed for a quantitative assessment of the scope, rate and impact of horizontally transmitted information on microbial evolution.     

Horizontal gene transfer in plants

Horizontal gene transfer (HGT) has played a major role in bacterial evolution and is fairly common in certain unicellular eukaryotes. However, the prevalence and importance of HGT in the evolution of multicellular eukaryotes remain unclear. Recent studies indicate that plant mitochondrial genomes are unusually active in HGT relative to all other organellar and nuclear genomes of multicellular eukaryotes. Although little about the mechanisms of plant HGT is known, several studies have implicated parasitic plants as both donors and recipients of mitochondrial genes. Most cases uncovered thus far have involved a single transferred gene per species; however, recent work has uncovered a case of massive HGT in Amborella trichopoda involving acquisition of at least a few dozen and probably hundreds of foreign mitochondrial genes. These foreign genes came from multiple donors, primarily eudicots and mosses. This review will examine the implications of such massive transfer, the potential mechanisms and consequences of plant-to-plant mitochondrial HGT in general, as well as the limited evidence for HGT in plant chloroplast and nuclear genomes.     

Horizontal gene transfer in chromalveolates

Background  

Horizontal gene transfer (HGT), the non-genealogical transfer of genetic material between different organisms, is considered a potentially important mechanism of genome evolution in eukaryotes. Using phylogenomic analyses of expressed sequence tag (EST) data generated from a clonal cell line of a free living dinoflagellate alga Karenia brevis, we investigated the impact of HGT on genome evolution in unicellular chromalveolate protists.     

Horizontal gene transfer in plants

Horizontal gene transfer (HGT) describes the transmission of genetic material across species boundaries. HGT often occurs in microbic and eukaryotic genomes. However, the pathways by which HGTs occur in multicellular eukaryotes, especially in plants, are not well understood. We systematically summarized more than ten possible pathways for HGT. The intimate contact which frequently occurs in parasitism, symbiosis, pathogen, epiphyte, entophyte, and grafting interactions could promote HGTs between two species. Besides these direct transfer methods, genes can be exchanged with a vector as a bridge: possible vectors include pollen, fungi, bacteria, viruses, viroids, plasmids, transposons, and insects. HGT, especially when involving horizontal transfer of transposable elements, is recognized as a significant force propelling genomic variation and biological innovation, playing an important functional and evolutionary role in both eukaryotic and prokaryotic genomes. We proposed possible mechanisms by which HGTs can occur, which is useful in understanding the genetic information exchange among distant species or distant cellular components.     

Horizontal gene transfer in trypanosomatids

Trypanosomes harbour a large number of structural and biochemical peculiarities. Kinetoplast DNA, mitochondrial RNA editing, the sequestration of glycolysis inside glycosomes and unique oxidative-stress protection mechanisms (to name but a few) are found only in the members of the order Kinetoplastida. Thus, it is not surprising that they have provoked much speculation about why and how such oddities have evolved in trypanosomes. However, the true reasons for their existence within the eukaryotic world are still far from clear. Here, Fred Opperdoes and Paul Michels argue that the trypanosome-specific evolution of novel processes and organization could only have been made possible by the acquisition of a large number of foreign genes, which entered a trypanosomatid ancestor through lateral gene transfer. Many different organisms must have served as donors. Some of them were viruses, and others were bacteria, such as cyanobacterial endosymbionts and non-phototrophic bacteria.     

Horizontal gene transfer in fungi

Reactive oxygen species (ROS) are a key feature of plant (and animal) defences against invading pathogens. As a result, plant pathogens must be able to either prevent their production or tolerate high concentrations of these highly reactive chemicals. In this review, we focus on plant pathogenic bacteria of the genus Pseudomonas and the ways in which they overcome the challenges posed by ROS. We also explore the ways in which pseudomonads may exploit plant ROS generation for their own purposes and even produce ROS directly as part of their infection mechanisms.     

Horizontal gene transfer in eukaryotes: The weak‐link model

The significance of horizontal gene transfer (HGT) in eukaryotic evolution remains controversial. Although many eukaryotic genes are of bacterial origin, they are often interpreted as being derived from mitochondria or plastids. Because of their fixed gene pool and gene loss, however, mitochondria and plastids alone cannot adequately explain the presence of all, or even the majority, of bacterial genes in eukaryotes. Available data indicate that no insurmountable barrier to HGT exists, even in complex multicellular eukaryotes. In addition, the discovery of both recent and ancient HGT events in all major eukaryotic groups suggests that HGT has been a regular occurrence throughout the history of eukaryotic evolution. A model of HGT is proposed that suggests both unicellular and early developmental stages as likely entry points for foreign genes into multicellular eukaryotes.