EDGE CMT: Defining the mechanistic roles of hyper-divergent regions in gene-by-environment interactions

Since Charles Darwin's studies of evolution, the field has been fascinated by adaptation or the process by which a species changes its behavior, physiology, or fitness to match a particular environment through genetic changes. Recently, the principal invstigator has found that genomes of many organisms have previously unknown and unseen regions that likely impact adaptation. This proposal will use cutting-edge genomics, genetic crosses, and high-throughput experiments to measure the effects of the genome on environmental adaptation. Using nematode species, these studies enable the first connections between specific genes that vary significantly among individuals to specific environmental factors. We hope to discover molecular details into how evolution impacts genomes. Additionally, we will use custom-built, low-cost microscopes and lesson plans adapted for middle and high school classrooms to run in-person nematode isolation experiments from the natural environment. Our focus will be to teach evolutionary principles and the fun of field scientific research. Short-read genome sequencing has transformed the fields of quantitative and population genetics. It is straightforward to generate whole-genome sequence (WGS) data for many organisms across a species. This explosion of WGS data across populations has led to the mapping of many quantitative trait loci (QTL), but very few of these QTL have been resolved to the level of quantitative trait genes or variants. This missing understanding of trait variation at the mechanistic level impedes our ability to make predictions of phenotype from genotype and to use the power of tractable organisms to translate generalizable results to less tractable species. Model species (e.g., yeast, worms, flies, and plants) have many QTL that have been resolved to genes and ultimate molecular mechanism, demonstrating generalizable features of trait variation across the tree of life. However, even in these tractable organisms, some regions of the genome are inaccessible using short-read WGS because they harbor variation that is far higher than genome-wide averages obfuscating genome alignments and variant calling. These hyper-divergent regions (HDRs) are found from plants to worms to humans and represent genomic “dark matter” because we know that they exist but their biological relevance is still mysterious. We will use long-read (LR) sequencing and de novo genome assembly to identify the highly variable genes or genes missing from reference genomes that play hypothesized roles in gene-by-environment (GxE) interactions, especially responses to pathogens, using high-throughput assays. These regions will be defined at the molecular level to enable phenotypic predictions and fully understand complex multigenic traits. 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.