Adaptation to the cost of resistance in a haploid clonally reproducing organism: the role of mutation, migration and selection

A model of compensatory evolution with respect to fungicide resistance in a haploid clonally reproducing fungus is developed in which compensatory mutations mitigate fitness costs associated with resistance. The role of mutation, migration and selection in invasion of rare genotypes when the environment changes from unsprayed to sprayed and from sprayed to unsprayed is analysed in detail. In some circumstances (ignoring back mutations) stable internal steady-state values for multiple genotypes can be obtained. In these cases a threshold value (f*) for the fraction of the population exposed to the fungicide can be derived for the transition between different steady-state conditions. Conditions are derived for invasion-when-rare of resistant genotypes at boundary equilibria established sometime after the onset of spraying and conversely of sensitive genotypes sometime after the cessation of spraying are derived. In these cases conditions are presented for (a) the invasion of a resistant genotype with a compensatory mutation (resistant-compensated) into a sensitive-uncompensated population that has re-equilibrated following the onset of spraying and (b) the invasion of a susceptible-uncompensated genotype into a resistant-compensated population that has re-equilibrated following the cessation of spraying, provided certain conditions are met. A resistant-compensated genotype may be fixed (or at near-fixation) in the population following a period of spraying, provided the mean intrinsic growth rate of the resistant-compensated genotype in a sprayed environment (over exposed and non-exposed parts of the population) is greater than that of the susceptible-uncompensated genotype. The fraction of the population exposed (the efficiency of spraying) is critical in this respect. However, it is possible for a sensitive-uncompensated genotype to invade provided there is no fitness gain associated with the resistant-compensated genotype, introduction by migration occurs following equilibration of the population to the new environment, and competitive effects are re-imposed when spraying ceases. We further derive a threshold level for the resident resistant-compensated population to reduce to following the cessation of spraying, such that the introduced susceptible-uncompensated genotype will invade. These results will be of use in determining the long-term persistence of resistance in a pathogen population once a fungicide is no longer effective and removed from use.     

A model of developmental evolution: selection, pleiotropy and compensation

Development and physiology translate genetic variation into phenotypic variation and determine the genotype-phenotype map, such as which gene affects which character (pleiotropy). Any genetic change in this mapping reflects a change in development. Here, we discuss evidence for variation in pleiotropy and propose the selection, pleiotropy and compensation model (SPC) for adaptive evolution. It predicts that adaptive change in one character is associated with deleterious pleiotropy in others and subsequent selection to compensate for these pleiotropic effects. The SPC model provides a unifying perspective for a variety of puzzling phenomena, including developmental systems drift and character homogenization. The model suggests that most adaptive signatures detected in genome scans could be the result of compensatory changes, rather than of progressive character adaptations.     

A coalescent model of background selection with recombination,demography and variation in selection coefficients

There is increasing evidence that background selection, the effects of the elimination of recurring deleterious mutations by natural selection on variability at linked sites, may be a major factor shaping genome-wide patterns of genetic diversity. To accurately quantify the importance of background selection, it is vital to have computationally efficient models that include essential biological features. To this end, a structured coalescent procedure is used to construct a model of background selection that takes into account the effects of recombination, recent changes in population size and variation in selection coefficients against deleterious mutations across sites. Furthermore, this model allows a flexible organization of selected and neutral sites in the region concerned, and has the ability to generate sequence variability at both selected and neutral sites, allowing the correlation between these two types of sites to be studied. The accuracy of the model is verified by checking against the results of forward simulations. These simulations also reveal several patterns of diversity that are in qualitative agreement with observations reported in recent studies of DNA sequence polymorphisms. These results suggest that the model should be useful for data analysis.     

Perturbation analysis of a two-locus model with directional selection and recombination

A population genetic two-locus model with additive, directional selection and recombination is considered. It is assumed that recombination is weaker than selection; i.e., the recombination parameter r is smaller than the selection coefficients. This assumption is appropriate for describing the effects of two-locus selection at the molecular level. The model is formulated in terms of ordinary differential equations (ODES) for the gamete frequencies x = (x ₁, x ₂, x ₃, x ₄), defined on the simplex S ₄. The ODEs are analyzed using first a regular pertubation technique. However, this approach yields satisfactory results only if r is very small relative to the selection coefficients and if the initial values x(0) are in the interior part of S ₄. To cope with this problem, a novel two-scale perturbation method is proposed which rests on the theory of averaging of vectorfields. It is demonstrated that the zeroth-order solution of this two-scale approach approximates the numerical solution of the model well, even if recombination rate is on the order of the selection coefficients.     

Sexual selection reveals a cost of pathogen resistance undetected in life-history assays

Mechanisms of resistance to pathogens and parasites are thought to be costly and thus to lead to evolutionary trade-offs between resistance and life-history traits expressed in the absence of the infective agents. On the other hand, sexually selected traits are often proposed to indicate “good genes” for resistance, which implies a positive genetic correlation between resistance and success in sexual selection. Here I show that experimental evolution of improved resistance to the intestinal pathogen Pseudomonas entomophila in Drosophila melanogaster was associated with a reduction in male sexual success. Males from four resistant populations achieved lower paternity than males from four susceptible control populations in competition with males from a competitor strain, indicating an evolutionary cost of resistance in terms of mating success and/or sperm competition. In contrast, no costs were found in larval viability, larval competitive ability and population productivity assayed under nutritional limitation; together with earlier studies this suggests that the costs of P. entomophila resistance for nonsexual fitness components are negligible. Thus, rather than indicating heritable pathogen resistance, sexually selected traits expressed in the absence of pathogens may be sensitive to costs of resistance, even if no such costs are detected in other fitness traits.     

The mitochondrial genome: mutation, selection and recombination

Within an individual, mitochondria must function in a range of tissue specific environments that are largely governed by expression of a particular suite of nuclear genes. Furthermore, mitochondrial proteins form large complexes with nuclear-encoded proteins to form the electron-transport system. These dynamics between mitochondrial and nuclear genomes have important implications in studies of within and among species genetic variation, and interpretation of disease phenotypes. Experimentally disrupting naturally occurring combinations of nuclear and mitochondrial genomes should provide insights into the coevolutionary dynamics among genomes.     

Mity model: Tetranychus urticae, a candidate for chelicerate model organism

Chelicerates (scorpions, horseshoe crabs, spiders, mites and ticks) are the second largest group of arthropods and are of immense importance for fundamental and applied science. They occupy a basal phylogenetic position within the phylum Arthropoda, and are of crucial significance for understanding the evolution of various arthropod lineages. Chelicerates are vectors of human diseases, such as ticks, and major agricultural pests, such as spider mites, thus this group is also of importance for both medicine and agriculture. The developmental genetics of chelicerates is poorly understood and a challenge for the future progress for many aspects of chelicerate biology is the development of a model organism for this group. Toward this end, we are developing a chelicerate genetic model: the two-spotted spider mite Tetranychus urticae. T. urticae has the smallest genome of any arthropod determined so far (75 Mbp, 60% of the size of the Drosophila genome), undergoes rapid development and is easy to maintain in the laboratory. These features make T. urticae a promising reference organism for the economically important, poorly studied and species-rich chelicerate lineage.     

Adaptation and the cost of complexity

Abstract.— Adaptation is characterized by the movement of a population toward a many-character optimum, movement that results in an increase in fitness. Here I calculate the rate at which fitness increases during adaptation and describe the curve giving fitness versus time as a population approaches an optimum in Fisher's model of adaptation. The results identify several factors affecting the speed of adaptation. One of the most important is organismal complexity—complex organisms adapt more slowly than simple ones when using mutations of the same phenotypic size. Thus, as Fisher foresaw, organisms pay a kind of cost of complexity. However, the magnitude of this cost is considerably larger than Fisher's analysis suggested. Indeed the rate of adaptation declines at least as fast as n^-1 , where n is the number of independent characters or dimensions comprising an organism. The present results also suggest that one can define an effective number of dimensions characterizing an adapting species.     

Fischerella thermalis: a model organism to study thermophilic diazotrophy,photosynthesis and multicellularity in cyanobacteria

Extremophiles - The true-branching cyanobacterium Fischerella thermalis (also known as Mastigocladus laminosus) is widely distributed in hot springs around the world. Morphologically, it has been...     

The effects of recombination,mutation and selection on the evolution of the Rp1 resistance genes in grasses

Plant immune genes, or resistance genes, are involved in a co‐evolutionary arms race with a diverse range of pathogens. In agronomically important grasses, such R genes have been extensively studied because of their role in pathogen resistance and in the breeding of resistant cultivars. In this study, we evaluate the importance of recombination, mutation and selection on the evolution of the R gene complex Rp1 of Sorghum, Triticum, Brachypodium, Oryza and Zea. Analyses show that recombination is widespread, and we detected 73 independent instances of sequence exchange, involving on average 1567 of 4692 nucleotides analysed (33.4%). We were able to date 24 interspecific recombination events and found that four occurred postspeciation, which suggests that genetic introgression took place between different grass species. Other interspecific events seemed to have been maintained over long evolutionary time, suggesting the presence of balancing selection. Significant positive selection (i.e. a relative excess of nonsynonymous substitutions (d_N/d_S>1)) was detected in 17–95 codons (0.42–2.02%). Recombination was significantly associated with areas with high levels of polymorphism but not with an elevated d_N/d_S ratio. Finally, phylogenetic analyses show that recombination results in a general overestimation of the divergence time (mean = 14.3%) and an alteration of the gene tree topology if the tree is not calibrated. Given that the statistical power to detect recombination is determined by the level of polymorphism of the amplicon as well as the number of sequences analysed, it is likely that many studies have underestimated the importance of recombination relative to the mutation rate.     

The dynamics of the rec-system in variable environments: haploid selection in a cyclical two-state environment

The dynamics of a 3-locus infinite population with non-overlapping generations and panmixia was studied. Loci are di-allelic: two loci affect fitness under cyclical symmetric haploid selection while the third one is a modifier of recombination (rec-modifier). Selection favors alternatively haplotypes AB and ab or Ab and aB. It has been proven that under alternating selection (when period of selection consists of two generations) a dominant suppressor of recombination is displaced and the allele for non-zero recombination becomes fixed within the population. For populations with inversion heterozygosity within the selective system (i.e. with zero recombination in heterozygote for rec-modifier and non-zero for homozygotes) fixation of one of the alleles (depending on the initial point) at the rec-modifier locus is predicted. For other values of recombination parameters, the behavior of the system was studied numerically. A full bifurcation picture of parameters was obtained. Many of the results related to the case of a two-generation period hold also in the case of longer period lengths.     

Density-dependent natural selection in Drosophila: Adaptation to adult crowding

The effects of adult crowding on two components of fitness were studied in three sets of Drosophila melanogaster populations, subjected to life-stage-specific, density-dependent natural selection in the laboratory for over 50 generations. Three days of crowding, early in adult life, were observed to increase mortality significantly during the episode of crowding, as well as decrease subsequent fecundity. Populations selected for adaptation to high adult densities suffered significantly lower mortality during episodes of adult crowding, as compared to populations selected specifically for adaptation to larval crowding, as well as control populations typically maintained at low larval and adult densities. Moreover, populations adapted to larval crowding seemed to be adversely affected by adult crowding to a greater extent than the controls, raising the possibility of trade-offs between adaptations to larval and adult crowding, respectively. Preliminary evidence suggests that the populations adapted to adult crowding may have evolved a propensity to stay away from the food medium, which is where most deaths occur when adults are crowded in culture vials. This revised version was published online in July 2006 with corrections to the Cover Date.     

Adaptation in the face of internal conflict: the paradox of the organism revisited

The paradox of the organism refers to the observation that organisms appear to function as coherent purposeful entities, despite the potential for within-organismal components like selfish genetic elements and cancer cells to erode them from within. While it is commonly accepted that organisms may pursue fitness maximisation and can be thought to hold particular agendas, there is a growing recognition that genes and cells do so as well. This can lead to evolutionary conflicts between an organism and the parts that reside within it. Here, we revisit the paradox of the organism. We first outline its conception and relationship to debates about adaptation in evolutionary biology. Second, we review the ways selfish elements may exploit organisms, and the extent to which this threatens organismal integrity. To this end, we introduce a novel classification scheme that distinguishes between selfish elements that seek to distort transmission versus those that seek to distort phenotypic traits. Our classification scheme also highlights how some selfish elements elude a multi-level selection decomposition using the Price equation. Third, we discuss how the organism can retain its status as the primary fitness-maximising agent in the face of selfish elements. The success of selfish elements is often constrained by their strategy and further limited by a combination of fitness alignment and enforcement mechanisms controlled by the organism. Finally, we argue for the need for quantitative measures of both internal conflicts and organismality.     

Adaptation of the functional system of the living organism to nonregular conjugated actions

A semiphenomenological approach to the study of the adaptation of a particular functional system of the living organism to nonregular changes in the environmental parameter conjugated with this system was suggested. It was shown that the behaviour of the functional system under these conditions is similar to that of a macroparticle in the rotational Brownian motion. In the adaptation process, a phase of superadaptation at the smallest nonregular actions was revealed. Some examples supporting the occurrence of the superadaptation phase are presented.     

The quest for a message: budding yeast, a model organism to study the control of pre-mRNA splicing

Removal of introns during pre-mRNA splicing is a critical processin gene expression, and understanding its control at both single-geneand genomic levels is one of the great challenges in Biology.Splicing takes place in a dynamic, large ribonucleoprotein complexknown as the spliceosome. Combining Genetics and Biochemistry,Saccharomyces cerevisiae provides insights into its mechanisms,including its regulation by RNA–protein interactions.Recent genome-wide analyses indicate that regulated splicingis broad and biologically relevant even in organisms with arelatively simple intronic structure, such as yeast. Furthermore,the possibility of coordination in splicing regulation at genomiclevel is becoming clear in this model organism. This shouldprovide a valuable system to approach the complex problem ofthe role of regulated splicing in genomic expression.      

SelSim: a program to simulate population genetic data with natural selection and recombination

SUMMARY: SelSim is a program for Monte Carlo simulation of DNA polymorphism data for a recombining region within which a single bi-allelic site has experienced natural selection. SelSim allows simulation from either a fully stochastic model of, or deterministic approximations to, natural selection within a coalescent framework. A number of different mutation models are available for simulating surrounding neutral variation. The package enables a detailed exploration of the effects of different models and strengths of selection on patterns of diversity. This provides a tool for the statistical analysis of both empirical data and methods designed to detect natural selection. AVAILABILITY: http://www.stats.ox.ac.uk/mathgen/software.html. SUPPLEMENTARY INFORMATION: http://www.stats.ox.ac.uk/mathgen/software.html.     

Adaptation to fluctuating environments in a selection experiment with Drosophila melanogaster

A fundamental question in life‐history evolution is how organisms cope with fluctuating environments, including variation between stressful and benign conditions. For short‐lived organisms, environments commonly vary between generations. Using a novel experimental design, we exposed wild‐derived Drosophila melanogaster to three different selection regimes: one where generations alternated between starvation and benign conditions, and starvation was always preceded by early exposure to cold; another where starvation and benign conditions alternated in the same way, but cold shock sometimes preceded starvation and sometimes benign conditions; and a third where conditions were always benign. Using six replicate populations per selection regime, we found that selected flies increased their starvation resistance, most strongly for the regime where cold and starvation were reliably combined, and this occurred without decreased fecundity or extended developmental time. The selected flies became stress resistant, displayed a pronounced increase in early life food intake and resource storage. In contrast to previous experiments selecting for increased starvation resistance in D. melanogaster, we did not find increased storage of lipids as the main response, but instead that, in particular for females, storage of carbohydrates was more pronounced. We argue that faster mobilization of carbohydrates is advantageous in fluctuating environments and conclude that the phenotype that evolved in our experiment corresponds to a compromise between the requirements of stressful and benign environments.