Collaborative Research: The role of gene copy number variation in determining detoxification capacity, individual fitness, and population dynamics in a vertebrate herbivore.

One of the grand challenges in biology is understanding how organisms respond to environmental change. Advances in genome sequencing technology are allowing unprecedented insight into the role of genetic variation in determining how organisms respond to environmental challenges. Specifically, genome sequencing has revealed substantial variation in the number of copies of ecologically important genes among individual genomes, wherein some individuals have very few copies of a gene while others have many. Yet, we understand very little about how gene copy number variation is maintained in the wild and how it influences survival and reproduction. The goal of this project is to discover how gene copy number variation at genes that aid in processing ingested toxins determines: 1) individual capacity to process toxins in food plants, 2) individual survival and reproduction in the wild, and 3) the ability of populations to persist in the face of environmental change. The PIs will achieve these goals by combining intensive field observations of individual mammalian herbivores (woodrats of the genus Neotoma) with the most modern approaches in genome sequencing, chemical analyses, and computer-based modeling. The students trained through this award will be uniquely positioned to pursue integrative careers with the skills to identify and manage the mechanisms that facilitate or hinder population persistence. The PIs will collaborate with local high school teachers to develop learning modules based on the themes of this research to augment public awareness of organismal response to environmental change, and to create a bridge to higher education. Understanding the genetic basis of phenotypic plasticity and adaptive evolution remains one of the central challenges in evolutionary biology. For vertebrate herbivores, one of the strongest sources of selection comes from exposure to the potentially toxic phytochemicals in the plants they consume. Insect herbivores appear to meet this challenge, in part, by diversification of gene copy number in detoxification loci. The PIs have recently discovered similar expansion of detoxification gene copy number in a group of herbivorous mammals, woodrats of the genus Neotoma. In this proposal, the PIs seek to understand the functional significance of copy number expansion by relating copy number variation (CNV) to detoxification capacity, individual fitness, and population dynamics across a natural environmental gradient. The PIs will examine these critical genotype-phenotype relationships in a hybrid zone between Neotoma fuscipes and N. macrotis. Hybrid zones offer a unique opportunity to study the causes and consequences of CNV because high rates of admixture generate individuals with novel structural variants whose dietary breadth and fitness can be tracked in the wild. In the hybrid zone population, the PIs will identify individual CNV; quantify the capacity of different copy number variants to detoxify phytochemicals; and predict how structural variation in detoxification gene families interacts with other environmental stressors (i.e., drought, high temperatures) to determine individual fitness and the capacity of populations to respond to environmental change. This study will be among the first to directly link structural genetic variation to dietary and detoxification phenotypes and their fitness consequences in the wild. This award was co-funded by Evolutionary Processes in BIO/DEB. 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.