An overarching theme of our research has been the process of adaptation to strong, and known selective pressures. Working on several systems including immunity in plants and bacteria and insecticide resistance in Drosophila our work has aimed to synthesize experiments and theory to elucidate how organisms adapt to these pressures.
The maintenance of Genetic Diversity in Host-Pathogen Interactions
In both plant and animal populations, the genes underlying immunity to pathogens tend to be among the most diverse (if not the most diverse) in the respective genomes. For the past several years, a central goal of our research has been determining the molecular and selective forces that generate and maintain this diversity.
One of the most striking examples of persistent resistance diversity can be found in plant resistance genes in which polymorphisms for resistance and susceptibility are maintained both within and across populations.
Polymorphisms at the resistance gene RPS5 are maintained in Arabidopsis thaliana populations across Europe (TL Karasov et al., Nature 2014)
Given that immune genes are diverse in host populations, what is the impact of this diversity on the pathogen populations? One could hypothesize that the immune diversity would prevent the emergence of single pathogenic lineages. In our recent Cell Host Microbe paper, we analyzed the genetic diversity of bacterial pathogens of the genus Pseudomonas in A. thaliana populations (TL Karasov et al., Cell Host Microbe 2018). Contrary to what has been observed in agriculture, the wild plant populations showed extensive pathogenic genetic and phenotypic diversity. Several of our current efforts are focused on determining the genetic and environmental forces that prevent single lineages from spreading.
In wild A. thaliana populations we do not see outbreaks of single pathogenic lineages. Instead, we observe extensive genetic diversity of the pathogen (TL Karasov et al., Cell Host Microbe 2018).
Association mapping pathogenicity traits in bacteria
We have observed extensive phenotypic diversity in the pathogens we collect from wild A. thaliana populations and have determined significant host-microbe genetype interactions underlying these differences. A current effort involves identifying the genetic changes in the pathogen that underly this phenotypic diversity.
To determine the genetic basis of differences in pathogenicity, we combine genomic and phentoypic screening to understand which genetic variants and which molecular phenotypes are responsible for the observed differences. Comparative genomics and transposon-sequencing (pooled saturation mutagenesis libraries) enable use to determine the genes important for survival in the plant. Genome wide association mapping further enables identification of genes important for pathogenicity traits.
High throughput infection assays enable us to test the effect of many strains on plant growth. In this plate, each plant is infected with a different strain.
Looking to the future, we plan to continue to develop and synthesize methods for mapping traits in bacterial.
Once we understand which loci underly strain-level differences in phenotype, we can then begin to analyse how these genes evolve in populations, and what limits the spread of single pathogen genotypes.