High-density SNP array and genome sequencing reveal signatures of selection in a divergent selection rat model for aerobic running capacity

We have previously established two lines of rat for studying the functional basis of aerobic exercise capacity (AEC) and its impact on metabolic health. The two lines, high capacity runners (HCR) and low capacity runners (LCR), have been selectively bred for high and low intrinsic AEC, respectively. They were started from the same genetically heterogeneous population and have now diverged in both AEC and many other physiological measures, including weight, body composition, blood pressure, body mass index, lung capacity, lipid and glucose metabolism, and natural life span. In order to exploit this rat model to understand the genomic regions under differential selection within the two lines, we used SNP genotype and whole genome pooled sequencing data to identify signatures of selection using three different statistics: runs of homozygosity, fixation index, and aberrant allele frequency spectrum, and developed a composite score that combined the three signals. We found that several pathways (ATP transport and fatty acid metabolism) are enriched in regions under differential selection. The candidate genes and pathways under selection will be integrated with the previous mRNA expression data and future F2 QTL results for a multi-omics approach to understanding the biological basis of AEC and metabolic traits.