EAGER: Establishing the genetic basis of hibernation by building and utilizing a next-generation genomics resource for the model hibernator, the thirteen-lined ground squirrel

Stanford University, Stanford CA

Investigators

Abstract

Hibernation is extraordinarily dynamic and extreme for mammals. To minimize energy expenditures during cool seasons, mammalian hibernators enter into a state of torpor, whereby physiological processes, including metabolic, respiratory and heart rates, are dramatically reduced, and body temperature is lowered to near or even below freezing. However, torpor is not continuous for the whole of hibernation but is instead punctuated by brief, but metabolically intense, arousals back to basal physiology. The molecular mechanisms that drive these cycles of torpor and arousal, in addition to the components underlying the annual cycle of hibernation, remain poorly understood. To better identify the genetic elements driving hibernation, this project will develop an enabling high-quality genomics resource for the model hibernator, the 13-lined ground squirrel. Once completed, the investigators will use this resource to detect genetic variants associated with hibernation traits, leading to new insight about the genetics of these physiological extremes. This project aligns the broader goals of the NSF by training and educating the next generation of scientists and establishing new partnerships. Collaborating with Stanford's Center for Computational, Evolutionary and Human Genomics, the investigators will develop a hibernation-specific lesson aimed at educating and encouraging STEM career entrance for middle school students from socioeconomically disadvantaged and ethnically underrepresented backgrounds. This project will also train a female postdoctoral scholar and an undergraduate researcher. Finally, this project will develop a partnership with the National Institute of Standards and Technology and enable comparative analyses with researchers assembling genomes of other mammals. The goal of this study is to build a genomics framework to establish the genetic basis hibernation. The investigators will first develop a high quality de novo assembly for the model hibernator, the 13-lined ground squirrel, Ictidomys tridecemlineatus. The current ground squirrel assembly is of draft quality, containing thousands of contigs and scaffolds, which makes genetic mapping of traits challenging. Using cutting-edge genomics techniques, both long-range and long-read data will be generated, which will increase the lengths of, and close gaps between, both contigs and scaffolds. These resulting scaffolds will be assembled onto chromosomes via linkage mapping. The linkage map will be created using a genotype-by-sequencing strategy to generate Single Nucleotide Polymorphic (SNP) markers in full-sibling families, which will be assigned into linkage groups and used to orient and order the scaffolds. Finally, the investigators will test the hypothesis that hibernation-related traits are genetically heritable. Genetic variation will be characterized in 150+ 13-lined ground squirrels. Narrow sense heritability of hibernation-related traits, measured from body-temperature telemetry records, will be estimated from related squirrels using genotype data. A quantitative trait loci analysis, enabled by the completion of the genome and linkage map, will be performed to identify specific variants associated with genetically heritable traits. Study results will be published in peer-reviewed journals and presented at scientific meetings.