Comparative Analyses Reveal the Genetic Mechanism of Ambergris Production in the Sperm Whale Based on the Chromosome-Level Genome

SIMPLE SUMMARY: The sperm whale (Physeter macrocephalus) is famous for the production of ambergris, while the underlying mechanism remains little known. In this study, comparative genomics analyses based on the chromosome-level genome of the sperm whale were performed. The expanded gene families and positive selected genes (PSGs) were found to be functionally enriched in biological pathways related to steroids, terpenoids, aldosterone, etc. Meanwhile, two predicted damaging missense mutations were found in the PSG LIPE that were important in the lipid and cholesterol metabolism. Furthermore, the HSD and CYP genes were mapped to the chromosome of the sperm whale, and phylogenetic analysis of CYP genes found relatively expanded subfamilies related to steroid and xenobiotics metabolism. Hence, these results may shed light on the genetic mechanism of ambergris production in sperm whales. ABSTRACT: Sperm whales are a marine mammal famous for the aromatic substance, the ambergris, produced from its colon. Little is known about the biological processes of ambergris production, and this study aims to investigate the genetic mechanism of ambergris production in the sperm whale based on its chromosome-level genome. Comparative genomics analyses found 1207 expanded gene families and 321 positive selected genes (PSGs) in the sperm whale, and functional enrichment analyses suggested revelatory pathways and terms related to the metabolism of steroids, terpenoids, and aldosterone, as well as microbiota interaction and immune network in the intestine. Furthermore, two sperm-whale-specific missense mutations (Tyr393His and Leu567Val) were detected in the PSG LIPE, which has been reported to play vital roles in lipid and cholesterol metabolism. In total, 46 CYP genes and 22 HSD genes were annotated, and then mapped to sperm whale chromosomes. Furthermore, phylogenetic analysis of CYP genes in six mammals found that CYP2E1, CYP51A and CYP8 subfamilies exhibited relative expansion in the sperm whale. Our results could help understand the genetic mechanism of ambergris production, and further reveal the convergent evolution pattern among animals that produce similar odorants.