PROJECT SUMMARY Innate immune receptors from the NLR protein family control basic organism-organism interactions across kingdoms, including incompatibility within a species. Current availability of genomic biodiversity allows us to examine patterns of innate immune receptor evolution. I propose that adaptive immunity has evolved by adopting subsets of proteins domains already present in innate immunity as well as their diversification mechanisms to act somatically in specialized cells. Testing this hypothesis through comparative genomics will be paradigm-shifting to our understanding of immune system evolution. To do this, we will examine evolution of protein domains involved in innate immunity across all available eukaryotic genomes, determine sources of genomic diversity and how they change with the re-current evolution of adaptive immunity across independent lineages. To test that there are targeted diversity generation mechanisms acting on NLRs at the population level, we will examine patterns of NLR evolution on multiple scales, including cross-kingdom analyses. We will test diversification mechanisms acting on them within species lacking adaptive immunity, including model plants and fungi. In parallel, we will experimentally test involvement of NLRs in fungal immunity, which has been proposed but yet to be experimentally validated. Finally, we will conduct experimental evolution on both NLRs and their ligands to collect data for modeling how new binding specificities arise on the population scale. Altogether, this project will fill in important gaps in understanding the evolution of innate immune systems, including our own.

PROJECT NARRATIVE Innate immunity is encoded in germline, yet on population level it is sufficient to recognize any pathogen even in absence of adaptive immunity. Exactly how new recognition specificities arise in innate immune receptors remain unknown. This project will address this fundamental gap and develop experimental and computational approaches to understand the evolution of innate immunity.