3.4 Specialized metabolism to adapt an obligate parasitic life
The scabies mite burrows into the skin of its host, and then resides in the lower epidermis close to the dermis, using host skin and intracellular fluid (lymph) that seeps into the burrow as food (Estes et al. , 1983; Neste & Lachapelle, 1981; Van Neste, 1984). Compared with the other eight species genes in specific families to S. scabiei were significantly enriched in protein metabolic-related GO categories, especially in proteolysis, serine-type peptidase activity, serine-type endopeptidase activity, cysteine-type peptidase activity, peptidase activity, and endopeptidase activity (Figure 4 ). KEGG analysis results showed categories associated with the digestive system (Protein digestion and absorption, and Pancreatic secretion), lipid metabolism (Fatty acid metabolism, and Biosynthesis of unsaturated fatty acids), transport and catabolism (Lysosome) and cell growth and death (Apoptosis) (Figure 4 ) were also highly enriched. These results reflected that S. scabiei var. cuniculi may underwent natural selection pressure by living in mammalian skin, evolved to have better ability of digesting proteins to break through the skin barrier and migrate in the epidermis, and most importantly, to meet the requirement of nutrition.
Besides, genes in the families that were shared only by ectoparasite scabies mite and Tropilaelaps mite are highly enriched in the biological process of cellular nitrogen compound metabolic process and nitrogen compound metabolic process (Figure S8-S9 ), probably related to carnivorous diets of both scabies mite andTropilaelaps mite. These genes were also enriched in KEGG pathway of human diseases, such as Alzheimer’s disease, Arrhythmogenic right ventricular cardiomyopathy (ARVC), Dilated cardiomyopathy, and Cardiac muscle contraction (Figure S8; Table S15 ). We speculated that the enhancement of heart muscle-like function is an adaption of the aerobic nature of scabies mites in the hypoxic skin environment (Arlian et al. , 1988).
Scabies mites have been known to well adapted to live in the epidermis of the skin, protecting them from the environment. According to expansion and contraction analysis, three gene families were expanded, and 34 gene families were contacted. The primary contributor to the acquisition of new functions and physiology is gene duplication (Nasvall et al. , 2012). The three expanded gene families including the vitamin D-binding protein (46 genes), synaptotagmin (12 genes) and HAUS complex (7 genes). The vitamin D-binding protein is the major binding/transport protein for all vitamin D metabolites (Bouillon et al. , 2020), genes in synaptotagmin family encode proteins that regulate calcium-dependent membrane fusion events (Wolfes & Dean, 2020), both were associated with enhanced absorption ability of nutrients. Among the 34 contracted gene families in scabies mites, genes were over-represented in the process of materials transport (Tables S16-17 ). We discovered four gene families that implicated in digestion, detoxification and transport of xenobiotics, including cytochrome P450 (CYP), carboxyl/cholinesterases (CCE), glutathione-S-transferase genes and ATP-binding cassette transporter C group and found unique scabies mite composition (Tables 2-3; Table S19-S20) . A total of only 25 cytochrome P450 (CYP) genes in Sarcoptes scabiei , followed byPediculus humanus (36 genes), T. mercedesae (42 genes), and Apis mellifera (46 genes) (Table 2 ); of which the number of genes in CYP4 clan being close to the number of counterparts in A. mellifera (4 genes), but far less than the number found in other mites (16~23 genes); members of CYP2 clan (three genes) and Mito clan (three genes) have orthologs inDrosophila melanogaster (Figure S10 ), indicating that scabies mites only retain the genes that support basic life. A notable contraction is also found in the family of carboxyl/cholinesterases (CCE) that include 11 genes compared with other three mites (31-69 genes), and 6 genes in subclass acetylcholinesterase (AChEs) compared with 22–59 genes in other mites (Table 3 ). Although the total number of ABC transporters remain the same, we discovered 14 multidrug resistance proteins that belong to the ATP-binding cassette (ABC) transporters (class C), while other mites have 20–39 genes (Table S18 and Figure S11 ). Finally, scabies mites have 13 glutathione-S -transferase genes (Table S19 and Figure S12 ) that can be assigned to four subfamilies: Delta/Epsilon (4 genes), Mu (6 genes), Zeta (1 gene), and Kappa (2 genes), interestingly, both mu and kappa appear to be tandem repeats in the genome. The relatively small number of P450 genes in honey bee was thought to be a consequence of the social organization of beehive, which shields the queen and larvae from environmental exposure to toxins (Claudianos et al. , 2006). It is likely that the extremely contracted detoxification genes in scabies mites might be the consequences of long time living in the epidermis of the skin, protect mites from environmental exposure to toxins.