Adult male muskrat (Ondatra zibethicus) has a pair of scent glands which secret musk to attract females during the breeding stage. The goal of the present study was to investigate the genetic mechanisms of musk secretion of muskrats at the whole genome level. Comparative genomics illustrated obvious expansion in 809 gene families, of which nine gene families played pivotal roles in steroid biosynthesis, possibly related to muskrat musk secretion. We identified 1112 positively selected genes (PSGs) in the muskrat, including estrogen receptor 1 (ER1), an important influencing factor to the weight and size of the scented glands of muskrats. HSD17B3, HSD17B4, CYP7B1 and CYP17B1, crucial to steroid hormone biosynthesis, were under strong positive selection in the muskrat, and phylogenetic analysis of HSD and CYP450 classes revealed high gene diversity. Functional enrichment revealed many pathways associated with musk secretion and/or growth and degeneration of scented gland significantly, such as peroxisome, PI3K-Akt signaling pathway, apoptosis, and prostate cancer. Two muskrat-specific missense mutations (Pro237Thr and Ser297Ile) were detected in LIPC, which were reported to be involved cholesterol metabolic process. More importantly, the missense mutations discovered in LIPC were classified as deleterious by PolyPhen-2, possibly affecting the musk secretion of muskrats.
