Host-pathogen Coevolution Research Articles

Reference Assembly and Annotation of the Pyrenophora teres f. teres Isolate 0-1.

Pyrenophora teres f. teres, the causal agent of net form net blotch (NFNB) of barley, is a destructive pathogen in barley-growing regions throughout the world. Typical yield losses due to NFNB range from 10 to 40%; however, complete loss has been observed on highly susceptible barley lines where environmental conditions favor the pathogen. Currently, genomic resources for this economically important pathogen are limited to a fragmented draft genome assembly and annotation, with limited RNA support of the P. teres f. teres isolate 0-1. This research presents an updated 0-1 reference assembly facilitated by long-read sequencing and scaffolding with the assistance of genetic linkage maps. Additionally, genome annotation was mediated by RNAseq analysis using three infection time points and a pure culture sample, resulting in 11,541 high-confidence gene models. The 0-1 genome assembly and annotation presented here now contains the majority of the repetitive content of the genome. Analysis of the 0-1 genome revealed classic characteristics of a “two-speed” genome, being compartmentalized into GC-equilibrated and AT-rich compartments. The assembly of repetitive AT-rich regions will be important for future investigation of genes known as effectors, which often reside in close proximity to repetitive regions. These effectors are responsible for manipulation of the host defense during infection. This updated P. teres f. teres isolate 0-1 reference genome assembly and annotation provides a robust resource for the examination of the barley–P. teres f. teres host–pathogen coevolution.

Inference of the phylogenetic diversity and population structure of Xanthomonas campestris affecting Brassicaceae using a multilocus sequence typing‐based approach

Xanthomonas campestris pathovars are widely distributed throughout the globe and have a broad host range, causing severe economic losses in the food and ornamental crucifers markets. Using an approach based on multilocus sequence typing, phylogenetic diversity and population structure of a set of 75 Portuguese and other Xanthomonas campestris isolates from several cruciferous hosts were assessed. Although this population displayed a major clonal structure, neighbour‐net phylogenetic analysis highlighted the presence of recombinational events that may have driven the ecological specialization of X. campestris with different host ranges within the Brassicaceae family. A high level of genetic diversity within and among X. campestris pathovars was also revealed, through the establishment of 46 sequence types (STs). This approach provided a snapshot of the global X. campestris population structure in cruciferous host plants, correlating the existing pathovars with three distinct genetic lineages. Phylogenetic relationships between the founder genotype and remaining isolates that constitute the X. campestris pv. campestris population were further clarified using goeBURST algorithm. Identification of an intermediate link between X. campestris pv. campestris and X. campestris pv. raphani provided new insights into the mechanisms driving the differentiation of both pathovars. Wide geographic distribution of allelic variants suggests that evolution of X. campestris as a seedborne pathogen was not shaped by natural barriers. However, as Portuguese isolates encompass 26 unique STs and this country is an important centre of domestication of Brassica oleracea crops, a strong case is made for its role as a diversification reservoir, most probably through host–pathogen coevolution.

Complete Genome Sequencing of Mycobacterium bovis SP38 and Comparative Genomics of Mycobacterium bovis and M. tuberculosis Strains.

Mycobacterium bovis causes bovine tuberculosis and is the main organism responsible for zoonotic tuberculosis in humans. We performed the sequencing, assembly and annotation of a Brazilian strain of M. bovis named SP38, and performed comparative genomics of M. bovis genomes deposited in GenBank. M. bovis SP38 has a traditional tuberculous mycobacterium genome of 4,347,648 bp, with 65.5% GC, and 4,216 genes. The majority of CDSs (2,805, 69.3%) have predictive function, while 1,206 (30.07%) are hypothetical. For comparative analysis, 31 M. bovis, 32 M. bovis BCG, and 23 Mycobacterium tuberculosis genomes available in GenBank were selected. M. bovis RDs (regions of difference) and Clonal Complexes (CC) were identified in silico. Genome dynamics of bacterial groups were analyzed by gene orthology and polymorphic sites identification. M. bovis polymorphic sites were used to construct a phylogenetic tree. Our RD analyses resulted in the exclusion of three genomes, mistakenly annotated as virulent M. bovis. M. bovis SP38 along with strain 35 represent the first report of CC European 2 in Brazil, whereas two other M. bovis strains failed to be classified within current CC. Results of M. bovis orthologous genes analysis suggest a process of genome remodeling through genomic decay and gene duplication. Quantification, pairwise comparisons and distribution analyses of polymorphic sites demonstrate greater genetic variability of M. tuberculosis when compared to M. bovis and M. bovis BCG (p ≤ 0.05), indicating that currently defined M. tuberculosis lineages are more genetically diverse than M. bovis CC and animal-adapted MTC (M. tuberculosis Complex) species. As expected, polymorphic sites annotation shows that M. bovis BCG are subjected to different evolutionary pressures when compared to virulent mycobacteria. Lastly, M. bovis phylogeny indicates that polymorphic sites may be used as markers of M. bovis lineages in association with CC. Our findings highlight the need to better understand host-pathogen co-evolution in genetically homogeneous and/or diverse host populations, considering the fact that M. bovis has a broader host range when compared to M. tuberculosis. Also, the identification of M. bovis genomes not classified within CC indicates that the diversity of M. bovis lineages may be larger than previously thought or that current classification should be reviewed.

Diversification of defensins and NLRs in Arabidopsis species by different evolutionary mechanisms

BackgroundGenes encoding proteins underlying host-pathogen co-evolution and which are selected for new resistance specificities frequently are under positive selection, a process that maintains diversity. Here, we tested the contribution of natural selection, recombination and transcriptional divergence to the evolutionary diversification of the plant defensins superfamily in three Arabidopsis species. The intracellular NOD-like receptor (NLR) family was used for comparison because positive selection has been well documented in its members. Similar to defensins, NLRs are encoded by a large and polymorphic gene family and many of their members are involved in the immune response.ResultsGene trees of Arabidopsis defensins (DEFLs) show a high prevalence of clades containing orthologs. This indicates that their diversity dates back to a common ancestor and species-specific duplications did not significantly contribute to gene family expansion. DEFLs are characterized by a pervasive pattern of neutral evolution with infrequent positive and negative selection as well as recombination. In comparison, most NLR alignment groups are characterized by frequent occurrence of positive selection and recombination in their leucine-rich repeat (LRR) domain as well negative selection in their nucleotide-binding (NB-ARC) domain. While major NLR subgroups are expressed in pistils and leaves both in presence or absence of pathogen infection, the members of DEFL alignment groups are predominantly transcribed in pistils. Furthermore, conserved groups of NLRs and DEFLs are differentially expressed in response to Fusarium graminearum regardless of whether these genes are under positive selection or not.ConclusionsThe present analyses of NLRs expands previous studies in Arabidopsis thaliana and highlights contrasting patterns of purifying and diversifying selection affecting different gene regions. DEFL genes show a different evolutionary trend, with fewer recombination events and significantly fewer instances of natural selection. Their heterogeneous expression pattern suggests that transcriptional divergence probably made the major contribution to functional diversification. In comparison to smaller families encoding pathogenesis-related (PR) proteins under positive selection, DEFLs are involved in a wide variety of processes that altogether might pose structural and functional trade-offs to their family-wide pattern of evolution.

Back to the future in a petri dish: Origin and impact of resurrected microbes in natural populations.

Current natural populations face new interactions because of the re‐emergence of ancient microbes and viruses. These risks come from the re‐emergence of pathogens kept in laboratories or from pathogens that are retained in the permafrost, which become available upon thawing due to climate change. We here focus on the effects of such re‐emergence in natural host populations based on evolutionary theory of virulence and long‐term studies, which investigate host–pathogen adaptations. Pathogens tend to be locally and temporally adapted to their co‐occurring hosts, but when pathogens from a different environment or different time enter the host community, the degree to which a new host–pathogen interaction is a threat will depend on the specific genotypic associations, the time lag between the host and the pathogen, and the interactions with native or recent host and pathogen species. Some insights can be obtained from long‐term studies using a resurrection ecology approach. These long‐term studies based on time‐shift experiments are essential to obtain insight into the mechanisms underlying host–pathogen coevolution at several ecological and temporal scales. As past pathogens and their corresponding host(s) can differ in infectivity and susceptibility, strong reciprocal selective pressures can be induced by the pathogen. These strong selective pressures often result in an escalating arms race, but do not necessarily result in increased infectivity over time. Human health can also be impacted by these resurrected pathogens as the majority of emerging infectious diseases are zoonoses, which are infectious diseases originating from animal populations naturally transmitted to humans. The sanitary risk associated with pathogen emergence from different environments (spatial or temporal) depends on a combination of socioeconomic, environmental, and ecological factors that affect the virulence or the pathogenic potential of microbes and their ability to infect susceptible host populations.

Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in the Field.

The coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and Europe is a paradigm for the evolution of a pathogen in a new host species. Genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. Using reverse genetics, we examined the roles of six selected mutations found in Australian field isolates of MYXV that fall in known or potential virulence genes. Several of these mutations occurred in genes previously identified as virulence genes in whole-gene knockout studies. Strikingly, no single or double mutation among the mutations tested had an appreciable impact on virulence. This suggests either that virulence evolution was defined by amino acid changes other than those analyzed here or that combinations of multiple mutations, possibly involving epistatic interactions or noncoding sequences, have been critical in the ongoing evolution of MYXV virulence. In sum, our results show that single-gene knockout studies of a progenitor virus can have little power to predict the impact of individual mutations seen in the field. The genetic determinants responsible for this canonical case of virulence evolution remain to be determined.IMPORTANCE The species jump of myxoma virus (MYXV) from the South American tapeti to the European rabbit populations of Australia and Europe is a canonical example of host-pathogen coevolution. Detailed molecular studies have identified multiple genes in MYXV that are critical for virulence, and genome sequencing has revealed the evolutionary history of MYXV in Australia and Europe. However, it has not been possible to categorically identify the key mutations responsible for the attenuation of or reversion to virulence during this evolutionary process. Here we use reverse genetics to examine the role of mutations in viruses isolated early and late in the Australian radiation of MYXV. Surprisingly, none of the candidate mutations that we identified as likely having roles in attenuation proved to be important for virulence. This indicates that considerable caution is warranted when interpreting the possible role of individual mutations during virulence evolution.

A new and updated resource for codon usage tables

BackgroundDue to the degeneracy of the genetic code, most amino acids can be encoded by multiple synonymous codons. Synonymous codons naturally occur with different frequencies in different organisms. The choice of codons may affect protein expression, structure, and function. Recombinant gene technologies commonly take advantage of the former effect by implementing a technique termed codon optimization, in which codons are replaced with synonymous ones in order to increase protein expression. This technique relies on the accurate knowledge of codon usage frequencies. Accurately quantifying codon usage bias for different organisms is useful not only for codon optimization, but also for evolutionary and translation studies: phylogenetic relations of organisms, and host-pathogen co-evolution relationships, may be explored through their codon usage similarities. Furthermore, codon usage has been shown to affect protein structure and function through interfering with translation kinetics, and cotranslational protein folding.ResultsDespite the obvious need for accurate codon usage tables, currently available resources are either limited in scope, encompassing only organisms from specific domains of life, or greatly outdated. Taking advantage of the exponential growth of GenBank and the creation of NCBI’s RefSeq database, we have developed a new database, the High-performance Integrated Virtual Environment-Codon Usage Tables (HIVE-CUTs), to present and analyse codon usage tables for every organism with publicly available sequencing data. Compared to existing databases, this new database is more comprehensive, addresses concerns that limited the accuracy of earlier databases, and provides several new functionalities, such as the ability to view and compare codon usage between individual organisms and across taxonomical clades, through graphical representation or through commonly used indices. In addition, it is being routinely updated to keep up with the continuous flow of new data in GenBank and RefSeq.ConclusionGiven the impact of codon usage bias on recombinant gene technologies, this database will facilitate effective development and review of recombinant drug products and will be instrumental in a wide area of biological research. The database is available at hive.biochemistry.gwu.edu/review/codon.

Assessing the genetic effects of rehabilitating harbor seals (Phoca vitulina) in the Wadden Sea using stochastic simulations

Rehabilitation of marine mammals with the intent of releasing them back into nature is carried out for several species. Rehabilitation can help supporting critically endangered species, increase public awareness, and serve scientific purposes, but rehabilitation also causes concern due to risk of introducing diseases into the wild populations and genetic changes from disruption of natural selection and host-pathogen co-evolution. In this study, we investigate another potential risk from rehabilitation that has not previously been considered, i.e., anthropogenic increase in population inbreeding level. For this purpose, we performed stochastic population viability analyses of the Wadden Sea harbor seal population using VORTEX. In the Wadden Sea, rehabilitation takes place in several rehabilitation centers, and many of the seals suffer from parasitic bronchopneumonia or are orphaned. Several studies have found a correlation between helminth infection and inbreeding level. Moreover, a relation between fitness traits such as pup survival and inbreeding has been demonstrated. On this basis, we assess the effects from rehabilitating relatively inbred seals on population size and genetic diversity. We find that releasing seals significantly affect population inbreeding level and to a lesser extent population size. The effect depends on the level of inbreeding in rehabilitated seals as well as the actual number of inbred seals released.

Experimental Evolution with Caenorhabditis Nematodes.

The hermaphroditic nematode Caenorhabditis elegans has been one of the primary model systems in biology since the 1970s, but only within the last two decades has this nematode also become a useful model for experimental evolution. Here, we outline the goals and major foci of experimental evolution with C. elegans and related species, such as C. briggsae and C. remanei, by discussing the principles of experimental design, and highlighting the strengths and limitations of Caenorhabditis as model systems. We then review three exemplars of Caenorhabditis experimental evolution studies, underlining representative evolution experiments that have addressed the: (1) maintenance of genetic variation; (2) role of natural selection during transitions from outcrossing to selfing, as well as the maintenance of mixed breeding modes during evolution; and (3) evolution of phenotypic plasticity and its role in adaptation to variable environments, including host–pathogen coevolution. We conclude by suggesting some future directions for which experimental evolution with Caenorhabditis would be particularly informative.

Evolution of antigenic diversity in the tick-transmitted bacterium Borrelia afzelii: a role for host specialization?

Antigenic diversity in pathogenic microbes can be a result of at least three different processes: diversifying selection by acquired immunity, host-pathogen coevolution and/or host specialization. Here, we investigate whether host specialization drives diversity at ospC (which encodes an immunodominant surface protein) in the tick-transmitted bacterium Borrelia afzelii. We determined prevalence and infection intensity of ospC strains in naturally infected wild mammals (rodents and shrews) by 454 amplicon sequencing in combination with qPCR. Neither prevalence nor infection intensity of specific ospC strains varied in a species-specific manner (i.e. there were no significant ospC×host species interactions). Rankings of ospC prevalences were strongly positively correlated across host species. Rankings of ospC infection intensities were correlated more weakly, but only in one case significantly <1. ospC prevalences in the studied mammals were similar to those in ticks sampled at the study site, indicating that we did not miss any mammal species that are important hosts for specific ospC strains. Based on this, we conclude that there is at best limited host specialization in B.afzelii and that other processes are likely the main drivers of ospC diversity.

Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954–1955) and between 2008–2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.

Using Population and Comparative Genomics to Understand the Genetic Basis of Effector-Driven Fungal Pathogen Evolution.

Epidemics caused by fungal plant pathogens pose a major threat to agro-ecosystems and impact global food security. High-throughput sequencing enabled major advances in understanding how pathogens cause disease on crops. Hundreds of fungal genomes are now available and analyzing these genomes highlighted the key role of effector genes in disease. Effectors are small secreted proteins that enhance infection by manipulating host metabolism. Fungal genomes carry 100s of putative effector genes, but the lack of homology among effector genes, even for closely related species, challenges evolutionary and functional analyses. Furthermore, effector genes are often found in rapidly evolving chromosome compartments which are difficult to assemble. We review how population and comparative genomics toolsets can be combined to address these challenges. We highlight studies that associated genome-scale polymorphisms with pathogen lifestyles and adaptation to different environments. We show how genome-wide association studies can be used to identify effectors and other pathogenicity-related genes underlying rapid adaptation. We also discuss how the compartmentalization of fungal genomes into core and accessory regions shapes the evolution of effector genes. We argue that an understanding of genome evolution provides important insight into the trajectory of host-pathogen co-evolution.

Analyses between Reproductive Behavior, Genetic Diversity and Pythium Responsiveness in Zingiber spp. Reveal an Adaptive Significance for Hemiclonality.

Mode of reproduction is generally considered to have long-range evolutionary implications on population survival. Because sexual reproduction produces genetically diverse genotypes, this mode of reproduction is predicted to positively influence the success potential of offspring in evolutionary arms race with parasites (Red queen) whereas, without segregation and recombination, the obligate asexual multiplication may push a species into extinction due to the steady accumulation of deleterious mutations (Muller’s ratchet). However, the extent of linearity between reproductive strategies, genetic diversity and population fitness, and the contributions of different breeding strategies to population fitness are yet to be understood clearly. Genus Zingiber belonging to the pan-tropic family Zingiberaceae represents a good system to study contributions of different breeding behavior on genetic diversity and population fitness, as this genus comprises species with contrasting breeding systems. In this study, we analyzed breeding behavior, amplified fragment length polymorphism diversity and response to the soft-rot pathogen Pythium aphanidermatum in 18 natural populations of three wild Zingiber spp.: Z. neesanum, Z. nimmonii, and Z. zerumbet, together with the obligately asexual cultivated congener, ginger (Z. officinale). Ginger showed an exceptionally narrow genetic base, and adding to this, all the tested cultivars were uniformly susceptible to soft-rot. Concordant with the postulates of Muller’s ratchet, the background selection may be continuously pushing ginger into the ancestral state, rendering it inefficient in host-pathogen coevolution. Z. neesanum and Z. nimmonii populations were sexual and genetically diverse; however, contrary to Red Queen expectations, the populations were highly susceptible to soft-rot. Z. zerumbet showed a hemiclonal breeding behavior. The populations inhabiting forest understory were large and continuous, sexual and genetically diverse, but were susceptible, whereas populations inhabiting the revenue land were fragmented and monoclonal, but were resistant. It may be possible that, when genetic recombination becomes at a premium due to the genetic constraints imparted by habitat fragmentation or pathogen pressure, Z. zerumbet

Phyllosiphon ari sp. nov. (Watanabea clade, Trebouxiophyceae), a new parasitic species isolated from leaves of Arum italicum (Araceae)&lt;br /&gt;

The trebouxiophycean genus Phyllosiphon contains unique green algae that thrive as endophytic parasites in the leaves of various members of the Araceae. The DNA sequences of the parasitic populations were originally acquired from infected leaves of subtropical Arisarum vulgare. However, several previous studies showed that the members of the Phyllosiphon clade also occur as free-living algae on various subaerial substrates across Europe. Phyllosiphon infection was also observed on the leaves of the temperate genus Arum, but no molecular data was available for these parasites. We recently found these parasites at a single sub-Mediterranean locality. These algae were genetically different from those previously obtained from Arisarum leaves on the basis of their 18S rDNA and rbcL gene sequences. In the present study, we describe this organism as a new species, Phyllosiphon ari. Phylogenetic differentiation of Phyllosiphon taxa, correlated with host specificity to different genera of the Araceae, suggests concerted host-pathogen co-evolution driving species diversification within this peculiar green algal lineage.

LRR-RLK family from two Citrus species: genome-wide identification and evolutionary aspects.

BackgroundLeucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subfamily of plant RLKs. The functions of most LRR-RLKs have remained undiscovered, and a few that have been experimentally characterized have been shown to have important roles in growth and development as well as in defense responses. Although RLK subfamilies have been previously studied in many plants, no comprehensive study has been performed on this gene family in Citrus species, which have high economic importance and are frequent targets for emerging pathogens. In this study, we performed in silico analysis to identify and classify LRR-RLK homologues in the predicted proteomes of Citrus clementina (clementine) and Citrus sinensis (sweet orange). In addition, we used large-scale phylogenetic approaches to elucidate the evolutionary relationships of the LRR-RLKs and further narrowed the analysis to the LRR-XII group, which contains several previously described cell surface immune receptors.ResultsWe built integrative protein signature databases for Citrus clementina and Citrus sinensis using all predicted protein sequences obtained from whole genomes. A total of 300 and 297 proteins were identified as LRR-RLKs in C. clementina and C. sinensis, respectively. Maximum-likelihood phylogenetic trees were estimated using Arabidopsis LRR-RLK as a template and they allowed us to classify Citrus LRR-RLKs into 16 groups. The LRR-XII group showed a remarkable expansion, containing approximately 150 paralogs encoded in each Citrus genome. Phylogenetic analysis also demonstrated the existence of two distinct LRR-XII clades, each one constituted mainly by RD and non-RD kinases. We identified 68 orthologous pairs from the C. clementina and C. sinensis LRR-XII genes. In addition, among the paralogs, we identified a subset of 78 and 62 clustered genes probably derived from tandem duplication events in the genomes of C. clementina and C. sinensis, respectively.ConclusionsThis work provided the first comprehensive evolutionary analysis of the LRR-RLKs in Citrus. A large expansion of LRR-XII in Citrus genomes suggests that it might play a key role in adaptive responses in host-pathogen co-evolution, related to the perennial life cycle and domestication of the citrus crop species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2930-9) contains supplementary material, which is available to authorized users.

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

The aim of this research is to gain insights on the progression timeline of osteoarticular tuberculosis (TB) in people from the Neolithic period by using skeletal traits that are independent of the bony lesions. The body proportions and postcranial mechanical strength of bones from two individuals from Liguria in northwestern Italy (Arene Candide 5, adolescent, and Arma dell’Aquila 1, adult), were compared with the rest of the Ligurian Neolithic skeletal series (45 individuals). If TB led to wasting of the skeleton and lack of normal function that endured for years, as often happens today, a clear signature of postcranial gracility and disruption of development should be apparent. Conversely, rapid progress of the disease would leave little systemic macroscopic change in the skeleton, except for the bony lesions directly caused by the TB pathogen, suggesting a different level of bacterial virulence in the past. The extreme biomechanical gracility observed in the lower limb of Arene Candide 5 suggests a period of compromised diaphyseal periosteal apposition during ontogeny due to metabolic disturbances likely linked to TB. Results suggest that, in Neolithic Liguria, TB in humans saw a slow, chronic progression, which is characteristic of diseases with long histories of host-pathogen co-evolution.

Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections.

The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an evolutionary arms race. Here we introduce a mathematical framework to study the coevolutionary dynamics between antibodies and antigens within a host. We focus on changes in the binding interactions between the antibody and antigen populations, which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection, and drift. We identify the critical viral and immune parameters that determine the distribution of antibody-antigen binding affinities. We also identify definitive signatures of coevolution that measure the reciprocal response between antibodies and viruses, and we introduce experimentally measurable quantities that quantify the extent of adaptation during continual coevolution of the two opposing populations. Using this analytical framework, we infer rates of viral and immune adaptation based on time-shifted neutralization assays in two HIV-infected patients. Finally, we analyze competition between clonal lineages of antibodies and characterize the fate of a given lineage in terms of the state of the antibody and viral populations. In particular, we derive the conditions that favor the emergence of broadly neutralizing antibodies, which may have relevance to vaccine design against HIV.

The evolution of sexual dimorphism and its potential impact on host-pathogen coevolution.

Sex and infection are intimately linked. Many diseases are spread by sexual contact, males are thought to evolve exaggerated sexual signals to demonstrate their immune robustness, and pathogens have been shown to direct the evolution of recombination. In all of these examples, infection is influencing the evolution of male and female fitness, but less is known about how sex differences influence pathogen fitness. A defining characteristic of sexual dimorphism is not only divergent phenotypes, but also a complex genetic architecture involving changes in genetic correlations among shared fitness traits, and differences in the accumulation of mutations-all of which may affect selection on an invading pathogen. Here, we outline the implications that the genetics of sexual dimorphism can have for host-pathogen coevolution and argue that male-female differences influence more than just the environment that a pathogen experiences.

Host persistence or extinction from emerging infectious disease: insights from white-nose syndrome in endemic and invading regions.

Predicting species' fates following the introduction of a novel pathogen is a significant and growing problem in conservation. Comparing disease dynamics between introduced and endemic regions can offer insight into which naive hosts will persist or go extinct, with disease acting as a filter on host communities. We examined four hypothesized mechanisms for host-pathogen persistence by comparing host infection patterns and environmental reservoirs for Pseudogymnoascus destructans (the causative agent of white-nose syndrome) in Asia, an endemic region, and North America, where the pathogen has recently invaded. Although colony sizes of bats and hibernacula temperatures were very similar, both infection prevalence and fungal loads were much lower on bats and in the environment in Asia than North America. These results indicate that transmission intensity and pathogen growth are lower in Asia, likely due to higher host resistance to pathogen growth in this endemic region, and not due to host tolerance, lower transmission due to smaller populations, or lower environmentally driven pathogen growth rate. Disease filtering also appears to be favouring initially resistant species in North America. More broadly, determining the mechanisms allowing species persistence in endemic regions can help identify species at greater risk of extinction in introduced regions, and determine the consequences for disease dynamics and host-pathogen coevolution.

Nosema spp. infections cause no energetic stress in tolerant honeybees.

Host-pathogen coevolution leads to reciprocal adaptations, allowing pathogens to increase host exploitation or hosts to minimise costs of infection. As pathogen resistance is often associated with considerable costs, tolerance may be an evolutionary alternative. Here, we examined the effect of two closely related and highly host dependent intracellular gut pathogens, Nosema apis and Nosema ceranae, on the energetic state in Nosema tolerant and sensitive honeybees facing the infection. We quantified the three major haemolymph carbohydrates fructose, glucose, and trehalose using high-performance liquid chromatography (HPLC) as a measure for host energetic state. Trehalose levels in the haemolymph were negatively associated with N. apis infection intensity and with N. ceranae infection regardless of the infection intensity in sensitive honeybees. Nevertheless, there was no such association in Nosema spp. infected tolerant honeybees. These findings suggest that energy availability in tolerant honeybees was not compromised by the infection. This result obtained at the individual level may also have implications at the colony level where workers in spite of a Nosema infection can still perform as well as healthy bees, maintaining colony efficiency and productivity.