The genetic basis of divergence in immune defense between species

University Of Kansas Center For Research Inc, Lawrence KS

Investigators

Abstract

All organisms get sick, but some get sicker than others. This is true within a species (some humans are more susceptible to certain infections than other humans), but it is also true between species (apes are not susceptible to infections that humans suffer from). These differences are likely to be genetic. In fact, we know that genes involved in the ability to fight infection are fast evolving between species – sometimes the fastest evolving genes across the entire genome. What we mostly lack, however, is a clear understanding of the genes that allow some species to fight infection better than others. This research aims to study how immune defense differs among closely related species using Drosophila as a model. This research is important for both basic scientific and applied reasons. Since immune genes are rapidly evolving, the approach allows for the study of evolutionary divergence between species at the genetic and molecular level. At the applied level, such rapid evolution to fight new infections might have other consequences such as an increased risk of autoimmune disease. So, understanding how different species evolve to fight infection will help elucidate how humans and other organisms must carefully tune their immune responses to fight infection, but also do as little harm to themselves as possible. The work will also provide training opportunities for high school students, undergraduates and graduate students. The project utilizes several Drosophila species to study how immune defense diverges between species. These species are closely related to Drosophila melanogaster, where much of the basic tenants of innate immunity were discovered. This allows the researchers to address several questions: Are some species generally better at fighting infection than their related species? Or is immune defense more pathogen-specific and the result of the history of host exposure? What are the genes involved in the divergence in immune defense against pathogens? Are these genes shared for different pathogens or specific for specific pathogens? Are the genes involved in immune divergence evolving under positive selection as is predicted by the genomic data? The first goal is to understand how related species differ in their ability to fight bacterial, fungal and viral infections. With that knowledge, researchers will dissect the genetic underpinnings of those differences using two complementary genetic approaches: quantitative trait locus mapping and allele specific gene expression analysis. Finally, researchers will confirm findings by genetically manipulating the different species – using CRISPR/Cas9 editing to move genes between species to determine whether those genes rescue a robust immune response. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.