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Maerkle, H.

Publications and source records attributed to Maerkle, H..

4 recordsLinked to original sources

Evolutionary implications of plant host interactions with a generalist pathogen

It is widely believed that eco-evolutionary feedbacks arising from host-pathogen interactions shape the number and frequency of resistance (R) genotypes and their allelic polymorphism. A subset of R genes exhibit unusually strong signatures of balancing selection, sometimes even existing as a trans-specific polymorphism. Here, we explore the role of alternative hosts on R gene evolution through a simple model of two closely related host species that share a single generalist pathogen. We ask (i) how shared interactions determine the R gene repertoires and polymorphism in each host and (ii) under which circumstances (trans-specific) polymorphism is maintained. Our results indicate that interactions with a generalist pathogen are more likely to sustain polymorphism at a shared R gene compared to the maintenance of polymorphism at R genes private to each host. The former can translate into trans-specific resistance gene polymorphism. Further, we observe that increasing the relative proportion of a single host species favors fixation of private resistance in the less common host, which stays effective because the pathogen tracks the more common host. Our model thus sheds light on how R gene dynamics are shaped by interactions with a shared generalist pathogen and the pathogens response to alternative hosts.

evolutionary biology↗

Inference of host-pathogen interaction matrices from genome-wide polymorphism data

Coevolution is defined as the evolutionary change in one antagonist (host) in response to changes in the other antagonist (pathogen). At the genetic level, these changes are determined by genotype x genotype (GxG) interactions. We build on a general theoretical model of a host-pathogen interaction to derive four indices to retrieve key features of GxG interactions. The four developed indices extract relevant information from polymorphism data of randomly sampled uninfected hosts as well as infected hosts and their respective pathogen strains. Using these indices as summary statistics in an Approximate Bayesian Computation method, we can show their power to discriminate between GxG interaction matrices. Second, we apply our ABC method to a SNP data set of 451 European humans and their infecting Hepatitis C Virus (HCV) strains supplemented by polymorphism data of 503 individuals from the 1,000 genomes project. As our indices encompass and extend previous natural co-GWAs we recover many of the associations previously reported for this dataset and infer their underlying interaction matrix. We reveal a new candidate gene for resistance to HCV in the human genome, and two groups of significant GxG associations exhibiting gene-for-gene interactions. We suggest that the inferred types of GxG interactions result from the recent expansion, adaptation and low prevalence of the HCV virus population in Europe. Significance statementWhy are some host individuals susceptible/resistant to infection by certain pathogen genotypes and others not? Understanding the genetic characteristics of genes driving host-pathogen interactions is crucial to predict epidemics. We develop four indices based on a mathematical model and build a Bayesian statistical method computing these indices on full genome data of infected hosts and their infecting pathogen strains and data of non-infected hosts. We can pinpoint the genes underlying host-pathogen interactions and infer their characteristics. Applying our framework to data from European humans and the Hepatitis C virus, we discover a new potential resistance gene in humans and reveal how the virus has adapted in the last 150 years to match the genetic diversity of the European human population.

evolutionary biology↗

Cross-Species association statistics for genome-wide studies of host and parasite polymorphism data

Uncovering the genes governing host-parasite coevolutionary interactions is of importance for disease management. The increasing availability of host and parasite full genome-data allows for cross-species genome-wide association studies based on the genomic data of in-fected hosts and their associated parasite strains sampled from natural populations (i.e. natural co-GWAs). Such studies focus on searching for cross-species allelic associations between pairs of host and parasite SNPs. We aim to quantify the power of natural co-GWAs to pinpoint loci under coevolution with respect to the intrinsic complexities of coevolutionary systems, such as the genetic specificity of the interaction and the temporal allele frequency changes resulting from the interaction. Therefore, we develop the cross-species association (CSA) and the cross-species prevalence (CSP) indices, the latter additionally incorporating genomic data from uninfected hosts. To provide an assessment of the statistical power of these indices, we analytically derive their genome-wide False Discovery Rates (FDR) based on the neutral site-frequency spectrum of the host and the parasite population. Using two coevolutionary models, we investigate under which parameter regimes these indices pin-point the coevolving loci. Under trench warfare dynamics, CSA and CSP are very accurate in pinpointing the loci under coevolution, while under arms race dynamics the power is limited especially for gene-for-gene interactions. Furthermore, we reveal that the combination of both indices across time samples is an indicator for the specificity of the interaction. Our results provide novel insights into the power and biological interpretation of natural cross-species association studies.

evolutionary biology↗

Inference of coevolutionary dynamics and parameters from host and parasite polymorphism data of repeated experiments

There is a long-standing interest in understanding host-parasite coevolutionary dynamics and associated fitness effects. Increasing amounts of genomic data for both interacting species offer a promising source to identify candidate loci and to infer the main parameters of the past coevolutionary history. However, so far no method exists to do so. By coupling a gene-for-gene model with coalescent simulations, we first show that three types of biological cost, resistance, infectivity and infection, define the allele frequencies at the internal equilibrium point of the coevolution model, which in return determine the strength of the selective signatures signatures at host and parasite loci. We apply an Approximate Bayesian Computation (ABC) approach on simulated datasets to infer these costs by jointly integrating host and parasite polymorphism data at the coevolving loci. To control for the effect of genetic drift on coevolutionary dynamics, we assume that 10 or 30 repetitions are available from controlled experiments or several natural populations. We study two scenarios: 1) the cost of infection and population sizes (host and parasite) are unknown while costs of infectivity and resistance are known, and 2) all three costs are unknown while populations sizes are known. Using the ABC model choice procedure, we show that for both scenarios, we can distinguish with high accuracy pairs of loci from host and parasite under coevolution from neutrally evolving loci, though the statistical power decreases with higher cost of infection. The accuracy of parameter inference is also very high under both scenarios especially when using both host and parasite data because parasite polymorphism data do inform on host costs and vice-versa. As the false positive rate to detect genes under coevolution is small, we suggest to use our method to identify host and parasite candidate loci for further functional studies.\n\nAuthor summaryIt is of importance for agriculture and medicine to understand host-parasite antagonistic coevolutionary dynamics and the deleterious associated fitness effects, as well as to reveal the genes underpinning these interactions. The increasing amount of genomic data for hosts and parasites offer a promising source to identify such candidate loci, but also to use statistical inference methods to reconstruct the past coevolutionary history. In our study we attempt to draw inference of the past coevolutionary history at key host and parasites loci using sequence data from several individuals and across several experimental replicates. We demonstrate that using a Bayesian statistical method, it is possible to estimate the parameters driving the interaction of hosts and parasites at these loci for thousands of generations. The main parameter that can be estimated is the fitness loss by hosts upon infection. Our method and results can be applied to experimental coevolution data with sequences at the key candidate loci providing enough repetitions and large enough population sizes. As a proof of principle, our results open the door to reconstruct past coevolutionary dynamics using sequence data of interacting species.

evolutionary biology↗