Biological adaptations in the Arctic cervid, the reindeer (Rangifer tarandus)

INTRODUCTION Reindeer ( Rangifer tarandus ) are naturally distributed across the Arctic and subarctic regions. Consequently, these animals have evolved to face numerous challenges, including exposure to severe cold, limited food availability in winter, and extremely prolonged light or dark periods. Unlike all other cervid species, both male and female reindeer annually grow deciduous antlers. Furthermore, reindeer are the only fully domesticated species among the Cervidae. However, little is known about the underlying genetic causes of these traits. RATIONALE We performed comparative genomic analyses between reindeer, other ruminant species, and a number of mammalian outgroups to identify rapidly evolving genes, positively selected genes, and reindeer-specific mutants. We further resequenced the genomes of three domestic reindeer from northern China and three wild reindeer from Northern Europe to validate that the reindeer-specific mutations are fixed in the species rather than individual polymorphisms. To support our computationally derived insights, we subsequently conducted in vitro functional experiments to investigate possible functional consequences of some of the reindeer-specific mutated genes. RESULTS We found two genes ( CYP27B1 and POR ) involved in the vitamin D metabolism pathway to be under positive selection in reindeer. Furthermore, our functional experiments validated that the two key enzymes (CYP27B1 and POR) exhibit much higher catalytic activity than that of the orthologs in goats and roe deer. We also identified fixed reindeer-specific mutations in genes that play a role in fat metabolism, including APOB and FASN . We showed that a mutation upstream of the reindeer CCND1 gene endows an extra functional binding motif to the androgen receptor and thus may result in female antler growth. In the circadian rhythm pathway, we observed that eight genes have reindeer-specific mutations and that four genes have been rapidly evolving. Among them, the Pro 1172 →Thr (P1172T) mutation in the reindeer PER2 causes loss of binding ability with CRY1, which can cause arrhythmicity. Finally, we found reindeer-specific mutations in 11 genes relating to development, migration, and differentiation of neural crest cells, probably accounting for the tameness of reindeer. CONCLUSION Our results reveal the genetic basis of a broad spectrum of the Arctic deer’s traits and provide a basis for understanding mammalian adaptive strategies to the Arctic. Our comparative genomic studies and functional assays identify a number of genes that exhibit functionality related to circadian arrhythmicity, vitamin D metabolism, docility, and antler growth, as well as genes that are uniquely mutated and/or are under positive selection. Our results may provide insights relevant to human health, including how the genetic response of vitamin D in reindeer affects bone and fat metabolism and how genes can affect circadian arrhythmicity.