A baseline model for the co-evolution of hosts and pathogens

The basic reproduction ratio (R (0)) is the expected number of secondary cases per primary in a totally susceptible population. In a baseline model, faced with an individual host strain pathogen virulence evolves to maximise R (0) which yields monomorphism. The basic depression ratio (D (0)) is the amount by which the total population is decreased, per infected individual, due to the presence of infection. Again, in a baseline model, faced with an individual pathogen strain host resistance evolves to minimise D (0) which yields monomorphism. With this in mind we analyse the community dynamics of the interaction between R (0) and D (0) and show that multi-strain co-existence (polymorphism) is possible and we discuss the possibility of stable cycles occuring within the co-existence states. We show for co-existence, the number of host and pathogen strains present need to be identical in order to achieve stable equilibria. For polymorphic states we observe contingencies (outcome dependent on initial conditions) between both point equilibrium and sustained oscillations. Invasion criteria for host and pathogen strains are identified.     

The basic depression ratio of the host: the evolution of host resistance to microparasites

The basic reproduction ratio R0 occupies a central position in the theory of host pathogen interactions. However, this quantity stresses the role of the pathogen. This paper proposes an additional, more host-centred char acterization using the basic depression ratio D0. This quantity is the number of host individuals per infected by which the infected host population is depressed below its uninfected level. This paper shows that a baseline criterion for the evolution of host resistance to microparasites is that resistance evolves to minimize D0. This parallels the result for pathogen virulence where R0 is maximized. The tension between these two criteria is noted. The framework established allows a discussion of trade-offs between aspects of the pathogen-free host biology and the host pathogen interaction. For certain linear and convex trade-offs it is shown that the strain with the lowest transmission parameter beta wins (despite the fact that it has the lowest intrinsic birth rate a). For corresponding concave trade-offs, either the strain with minimum beta and a or the strain with maximum beta and a wins. Finally the connection with the techniques of adaptive dynamics is made. Evolutionary singular points are shown to occur at extrema of D0. The evolutionary attainment of the results is discussed.     

Microevolution in biological control: Mechanisms, patterns, and processes

Microevolution may determine both the safety and efficacy of classical biological control. Despite a growing body of literature, there are several key unanswered questions regarding the role of evolution in biological control: (1) How common is local adaptation of natural enemies to their hosts or the environment in the native range? How critical is it for success of biological control to find locally adapted agents for importation? (2) Does adaptive evolution following introductions play an important role in biological control? (3) Do introductions of biological control agents impose bottlenecks in population size that reduce genetic variation, and is reduced genetic variation associated with low fitness and poor performance? (4) How great is the risk of evolution of host range of biological control agents? (5) What is the risk of target pests evolving resistance to biological control agents? If pests evolve increased resistance, will biological control agents evolve mechanisms to overcome that resistance? Here, we review the four fundamental processes of microevolution, and discuss how they interact in the context of biological control. We discuss our current state of knowledge regarding the outstanding questions, highlight the types of experiments that can address them, and suggest ways to use microevolution to define risks, and enhance efficacy and safety of biological control.     

A net reproductive number for periodic matrix models

We give a definition of a net reproductive number R (0) for periodic matrix models of the type used to describe the dynamics of a structured population with periodic parameters. The definition is based on the familiar method of studying a periodic map by means of its (period-length) composite. This composite has an additive decomposition that permits a generalization of the Cushing-Zhou definition of R (0) in the autonomous case. The value of R (0) determines whether the population goes extinct (R (0)<1) or persists (R (0)>1). We discuss the biological interpretation of this definition and derive formulas for R (0) for two cases: scalar periodic maps of arbitrary period and periodic Leslie models of period 2. We illustrate the use of the definition by means of several examples and by applications to case studies found in the literature. We also make some comparisons of this definition of R (0) with another definition given recently by Baca?r.     

Stability and selection in self-reproducing macromolecular systems

In this paper we develop stability criteria applicable to Eigen's model for the selection and evolution of biological macromolecules. We show that it is possible to characterize the time evolution of the macromolecular system by Lyapounov-like functionals. The Lyapounov method is used to discuss the general stability of the system and the metastable nature of the selected states are discussed.     

Recombination in HIV and the evolution of drug resistance: for better or for worse?

The rapid evolution of drug resistance remains a major obstacle for HIV therapy. The capacity of the virus for recombination is widely believed to facilitate the evolution of drug resistance. Here, we challenge this intuitive view. We develop a population genetic model of HIV replication that incorporates the processes of mutation, cellular superinfection, and recombination. We show that cellular superinfection increases the abundance of low fitness viruses at the expense of the fittest strains due to the mixing of viral proteins during virion assembly. Moreover, we argue that whether recombination facilitates the evolution of drug resistance depends critically on how resistance mutations interact to determine viral fitness. Contrary to the commonly held belief, we find that, under the most plausible biological assumptions, recombination is expected to slow down the rate of evolution of multi-drug-resistant virus during therapy.     

Characterization of In0 of Pseudomonas aeruginosa plasmid pVS1, an ancestor of integrons of multiresistance plasmids and transposons of gram-negative bacteria.

Many multiresistance plasmids and transposons of gram-negative bacteria carry related DNA elements that appear to have evolved from a common ancestor by site-specific integration of discrete cassettes containing antibiotic resistance genes or sequences of unknown function. The site of integration is flanked by conserved segments coding for an integraselike protein and for sulfonamide resistance, respectively. These segments, together with the antibiotic resistance genes between them, have been termed integrons (H. W. Stokes and R. M. Hall, Mol. Microbiol. 3:1669-1683, 1989). We report here the characterization of an integron, In0, from Pseudomonas aeruginosa plasmid pVS1, which has an unoccupied integration site and hence may be an ancestor of more complex integrons. Codon usage of the integrase (int) and sulfonamide resistance (sul1) genes carried by this integron suggests a common origin. This contrasts with the codon usage of other antibiotic resistance genes that were presumably integrated later as cassettes during the evolution and spread of these DNA elements. We propose evolutionary schemes for (i) the genesis of the integrons by the site-specific integration of antibiotic resistance genes and (ii) the evolution of the integrons of multiresistance plasmids and transposons, in relation to the evolution of transposons related to Tn21.     

Linking genetic change to community evolution: insights from studies of bacteria and bacteriophage

A major goal of community ecology is to link biological processes at lower scales with community patterns. Microbial communities are especially powerful model systems for making these links. In this article, we review recent studies of laboratory communities of bacteria and bacteriophage (viruses that infect bacteria). We focus on the ecology and evolution of bacteriophage-resistance as a case study demonstrating the relationship between specific genes, individual interactions, population dynamics, community structure, and evolutionary change. In laboratory communities of bacteria and bacteriophage, bacteria rapidly evolve resistance to bacteriophage infection. Different resistance mutations produce distinct resistance phenotypes, differing, for example, in whether resistance is partial or complete, in the magnitude of the physiological cost associated with resistance, and in whether the mutation can be countered by a host-range mutation in the bacteriophage. These differences determine whether a mutant can invade, the effect its invasion has on the population dynamics of sensitive bacteria and phage, and the resulting structure of the community. All of these effects, in turn, govern the community's response to environmental change and its subsequent evolution.     

BIOCOMPUTATION: Some history and prospects

At first glance, biology and computer science are diametrically opposed sciences. Biology deals with carbon based life forms shaped by evolution and natural selection. Computer Science deals with electronic machines designed by engineers and guided by mathematical algorithms. In this brief paper, we review biologically inspired computing. We discuss several models of computation which have arisen from various biological studies. We show what these have in common, and conjecture how biology can still suggest answers and models for the next generation of computing problems. We discuss computation and argue that these biologically inspired models do not extend the theoretical limits on computation. We suggest that, in practice, biological models may give more succinct representations of various problems, and we mention a few cases in which biological models have proved useful. We also discuss the reciprocal impact of computer science on biology and cite a few significant contributions to biological science.     

X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV-1 infection remain exclusive or at least dominant far from PHI

Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests. Clonal analysis was performed at baseline for env, RT and protease genes, and for HIV-DNA env gene during follow-up. Five patients were eligible. At baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2 patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all patients. For patient A, tropism remained R5 with concordance between phenotypic and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV-DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous X4-using population at baseline; tropism was unchanged at M1 and M18. In all patients, the initial MDR population was highly homogenous initially, supporting the early expansion of a monoclonal population and its long-term persistence. X4-tropic variants present at baseline were still exclusive (patients D and E) or dominant (at least one time point, patient C) far from PHI.     

Inclusive heritability: combining genetic and non‐genetic information to study animal behavior and culture

Phenotypic variance results from variation in biological information possessed by individuals. Quantitative geneticists often strive to partition out all environmental variance to measure heritability. Behavioral biologists and ecologists however, require methods to integrate genetic and environmental components of inherited phenotypic variance in order to estimate the evolutionary potential of traits, which encompasses any form of information that is inherited. To help develop this integration, we build on the tools of quantitative genetics and offer the concept of ‘inclusive heritability’ which identifies and unifies the various mechanisms of information transmission across generations. A controversial component of non‐genetic information is animal culture, which is the part of phenotypic variance inherited through social learning. Culture has the unique property of being transmitted horizontally and obliquely, as well as vertically. Accounting for cultural variation would allow us to examine a broader range of evolutionary mechanisms. Culture may, for instance, produce behavioral isolating mechanisms leading to speciation. To advance the study of animal culture, we offer a definition of culture that is rooted in quantitative genetics. We also offer four testable criteria to determine whether a trait is culturally inherited. These criteria may constitute a conceptual tool to study animal culture. We briefly discuss methods to partition out cultural variance. Several authors have recently called for ‘modernizing the modern synthesis’ by including non‐genetic factors such as epigenetics and phenotypic plasticity in order to more fully explain phenotypic evolution. Here, we further propose to broaden the concept of inheritance by incorporating the cultural component of behavior. Applying the concept of inclusive heritability may advance the integration of multiple forms of inheritance into the study of evolution.     

Evolution of pathogens towards low R0 in heterogeneous populations

Maximization of the basic reproduction ratio or R(0) is widely believed to drive the emergence of novel pathogens. The presence of exploitable heterogeneities in a population, such as high variance in the number of potentially infectious contacts, increases R(0) and thus pathogens that can exploit heterogeneities in the contact structure have an advantage over those that do not. However, exploitation of heterogeneities results in a more rapid depletion of the potentially susceptible neighbourhood for an infected host. Here a simple model of pathogen evolution in a heterogeneous environment is developed and placed in the context of HIV transmission. In this model, it is shown that pathogens may evolve towards lower R(0), even if this results in pathogen extinction. For sufficiently high transmissibility, two locally stable strategies exist for an evolving pathogen, one that exploits heterogeneities and results in higher R(0), and one that does not, and results in lower R(0). While the low R(0) strategy is never evolutionarily stable, invading strains with higher R(0) will also converge to the low R(0) strategy if not sufficiently different from the resident strain. Heterogenous transmission is increasingly recognized as fundamental to epidemiological dynamics and the evolution of pathogens; here, it is shown that the ability to exploit heterogeneity is a strategy that can itself evolve.     

The geometry and motion of reaction-diffusion waves on closed two-dimensional manifolds

Chemical or biological systems modelled by reaction diffusion (R.D.) equations which support simple one-dimensional travelling waves (oscillatory or otherwise) may be expected to produce intricate two or three-dimensional spatial patterns, either stationary or subject to certain motion. Such structures have been observed experimentally. Asymptotic considerations applied to a general class of such systems lead to fundamental restrictions on the existence and geometrical form of possible structures. As a consequence of the geometrical setting, it is a straightforward matter to consider the propagation of waves on closed two-dimensional manifolds. We derive a fundamental equation for R.D. wave propagation on surfaces and discuss its significance. We consider the existence and propagation of rotationally symmetric and double spiral waves on the sphere and on the torus. On leave of absence from: Department of Mathematics, Glasgow College of Technology, Cowcaddens Road, Glasgow G4 0BA, Scotland, UK     

Rapid evolution of reproductive proteins in abalone and Drosophila

Observations from different taxa, including plants, protozoa, insects and mammals, indicate that proteins involved in reproduction evolve rapidly. Several models of adaptive evolution have been proposed to explain this phenomenon, such as sexual conflict, sexual selection, self versus non-self recognition and pathogen resistance. Here we discuss the potential role of sexual conflict in the rapid evolution of reproductive genes in two different animal systems, abalone (Haliotis) and Drosophila. In abalone, we reveal how specific interacting sperm-egg proteins were identified and discuss this identification in the light of models for rapid protein evolution and speciation. For Drosophila, we describe the genomic approaches taken to identify male accessory gland proteins and female reproductive tract proteins. Patterns of protein evolution from both abalone and Drosophila support the predicted patterns of rapid protein evolution driven by sexual conflict. We stress however that other selective pressures may contribute to the rapid evolution that is observed. We conclude that the key to distinguishing between sexual conflict and other mechanisms of protein evolution will be an integration of genetic, experimental and theoretical data.     

Problematica old and new

Problematica are taxa that defy robust phylogenetic placement. Traditionally the term was restricted to fossil forms, but it is clear that extant taxa may be just as difficult to place, whether using morphological or molecular (nucleotide, gene or genomic) markers for phylogeny reconstruction. We discuss the kinds and causes of Problematica within the Metazoa, as well as criteria for their recognition and possible solutions. The inclusive set of Problematica changes depending upon the nature and quality of (homologous) data available, the methods of phylogeny reconstruction and the sister taxa inferred by their placement or displacement. We address Problematica in the context of pre-cladistic phylogenetics, numerical morphological cladistics and molecular phylogenetics, and focus on general biological and methodological implications of Problematica, rather than presenting a review of individual taxa. Rather than excluding Problematica from phylogeny reconstruction, as has often been preferred, we conclude that the study of Problematica is crucial for both the resolution of metazoan phylogeny and the proper inference of body plan evolution.     

A simple persistence condition for structured populations

The fundamental question in both basic and applied population biology of whether a species will increase in numbers is often investigated by finding the population growth rate as the largest eigenvalue of a deterministic matrix model. For a population classified only by age, and not stage or size, a simpler biologically interpretable condition can be used, namely whether R ₀, the mean number of offspring per newborn, is greater than one. However, for the many populations not easily described using only age classes, stage-structured models must be used for which there is currently no quantity like R ₀. We determine analogous quantities that must be greater than one for persistence of a general structured population model that have a similar useful biological interpretation. Our approach can be used immediately to determine the magnitude of changes and interactions that would either allow population persistence or would ensure control of an undesirable species.     

Long-term bed rest-induced reductions in stroke volume during rest and exercise: cardiac dysfunction vs. volume depletion.

Long-term head-down-tilt bed rest (HDT) causes cardiovascular deconditioning, attributed to reflex dysfunctions, plasma volume reduction, or cardiac impairments. Our objective with the present study was to evaluate the functional importance and relative contribution of these during rest and exercise in supine and upright postures. We studied six subjects before (baseline), during [days 60 (D60) and 113 (D113)], and after [recovery days 0 (R0), 3 (R3), and 15 (R15)] 120 days of -6 degrees HDT. We determined cardiac output, stroke volume (SV), mean arterial pressure, and heart rate during rest and exercise in supine and upright postures. Cardiac output and SV decreased significantly in all four conditions, but the time courses differed for rest and exercise. Upright resting SV was decreased by 24 +/- 9% at D60 compared with baseline but had recovered already at R3. Supine exercise SV decreased more slowly (by 5 +/- 8% at D60 and by 18 +/- 4% at D113) and recovered more slowly after HDT termination. Steady-state mean arterial pressure showed no changes. Heart rate had increased by 18 +/- 4% at D60 and had recovered partially at R3. Our data indicate that long-term HDT causes both a rapid, preload-dependent reduction in SV, most evident during rest in the upright position, and a more slowly developing cardiac dysfunction, most evident during supine exercise. However, the ability to maintain blood pressure and to perform sustained low levels of dynamic exercise is not influenced by HDT.     

Phosphorylation determines the calmodulin-mediated Ca2+ response and water permeability of AQP0

In Xenopus oocytes, the water permeability of AQP0 (P(f)) increases with removal of external calcium, an effect that is mediated by cytoplasmic calmodulin (CaM) bound to the C terminus of AQP0. To investigate the effects of serine phosphorylation on CaM-mediated Ca(2+) regulation of P(f), we tested the effects of kinase activation, CaM inhibition, and a series of mutations in the C terminus CaM binding site. Calcium regulation of AQP0 P(f) manifests four distinct phenotypes: Group 1, with high P(f) upon removal of external Ca(2+) (wild-type, S229N, R233A, S235A, S235K, K238A, and R241E); Group 2, with high P(f) in elevated (5 mm) external Ca(2+) (S235D and R241A); Group 3, with high P(f) and no Ca(2+) regulation (S229D, S231N, S231D, S235N, and S235N/I236S); and Group 4, with low P(f) and no Ca(2+) regulation (protein kinase A and protein kinase C activators, S229D/S235D and S235N/I236S). Within each group, we tested whether CaM binding mediates the phenotype, as shown previously for wild-type AQP0. In the presence of calmidazolium, a CaM inhibitor, S235D showed high P(f) and no Ca(2+) regulation, suggesting that S235D still binds CaM. Contrarily, S229D showed a decrease in recruitment of CaM, suggesting that S229D is unable to bind CaM. Taken together, our results suggest a model in which CaM acts as an inhibitor of AQP0 P(f). CaM binding is associated with a low P(f) state, and a lack of CaM binding is associated with a high P(f) state. Pathological conditions of inappropriate phosphorylation or calcium/CaM regulation could induce P(f) changes contributing to the development of a cataract.