4.2 Genetic basis of scabies mites to adapt an obligate and permanent parasitic life
As a permanent ectoparasitic mite, scabies mites have evolved from various levels. When we analyzed the mechanism that influenced morphology of the species in Acari, we found the Hox gene family divergence may cause the differences of body plan in superorder Acariformes and Parasiformes, especially the absence of Zen andAbd-A . For Chelicerate species like spiders and mites, Zenand Abd-A were reported to function in body plan of the prosoma and the opisthosoma (Hughes & Kaufman, 2002). Previous study showed that, the function of Zen has transferred from a Hox-like role to a role in the extraembryonic tissues due to the functional overlap with other Hox proteins (Hughes & Kaufman, 2002; Pick, 2016), thus pretended to be lost for species in the Acariformes that generally have small genomes (Table S25) . The expression of Abd-A and Abd-Breflects the differences in the insect abdomen, and Abd -Bacts to suppress Abd-A in posterior segments, and suppresses posterior segmentation (Celniker et al. , 1989; Jordi et al. , 1986; Karch et al. , 1990). Previous data supportted a model that inversion of the Abd-B locus results in the loss of Abd-A , and correlated with reduced trunk segmentation (Pace et al. , 2016), and in this study, the Hox clusters and transcription direction in S. scabiei , P. ovis and T. urticae implicated the same mechanisms for the trunk segmentation of species in Acariforms. These results indicated that the morphological evolution correlated with the loss of specific Hox genes.
Genes in families specific to scabies mainly enriched in nutrition absorption and digestion of proteins and lipids. And genes in families of cytochrome P450 (CYP), carboxyl/cholinesterases (CCE), and multidrug resistance proteins of the ATP-binding cassette transporter C group are strikingly contracted, and members in these families were reported to function in a wide range of detoxification events (Dermauw et al. , 2013; Enayati et al. , 2005; X. Li et al. , 2007). Scabies mite lives in the epidermis of the mammal skin, which is a relatively enclosed stable environment. Compared with P. humanus andT. mercedesae that live on the surface of the hosts, scabies mites have limited chances of encountering toxicants than other ectoparasites, thus the strikingly contracted gene families that are of important in metabolizing toxic xenobiotics in insects and the acquisition of insecticide resistance indicated a less effective detoxification system and an adaption to the enclosed environment.
Genetic basis of variant divergence and cross-infestivity
To date, there is no well-accepted standard to define subspecies or variants of mites, especially by using limited gene markers. In this study, we considered mites from different hosts as variants based on results of PCA and phylogenetic analysis. Although there is no direct evidence of host shift, comparative genomics analysis may provide clues for the cross-infectivity of these mites. It is known that S. scabiei reside at the interface of stratum lucidum and stratum granulosum (Estes et al. , 1983; Neste & Lachapelle, 1981; Van Neste, 1984), and mites have to burrow deep through stratum corneum to get to their destination, therefore, the thickness of stratum corneum may partly reflected the difficulties of mites to break through the barriers of the skin.
The selection signal between human mites/pig mites, human mite/dog mites quantitatively reflected the adaption to the new host in shaping the genome. Genes enriched in “cysteine-type peptidase activity” and “apoptosis” mainly encode Sar s1 allergen scabies mite inactive cysteine proteases (SMIPP-Cs). The function of these proteins is promoting blood coagulation and changing the structure and density of fibrin clots, making them resistant to fibrinolysis, thus protecting scabies mites from the host immune system (Fernando et al. , 2021). These functions were thought to contribute to parasitic lifestyle. Neuroactive ligand-receptor interaction (18 genes) is a function of environmental information processing (Table S28 ). Most of the group 3 allergen SMIPP-S genes occur in tandem, studies have shown that these proteins might function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge (Fischer et al. , 2009). Besides, the presence of receptors, such as the olfactory receptor, rhodopsin-like G protein-coupled receptor, and the 5‑hydroxytryptamine receptor family, suggested that scabies mites in omnivorous pigs have evolved to have a better ability to process environmental information, and thus adapted to a more complicated pig skin environment.
A previous study reported that mites from scabies-infected dogs can establish permanent infections on domestic rabbits and these mites can then re-infect dogs (Nicoli et al. , 2008). Interestingly, it is reported that the human and the pig stratum corneum share very similar lipid types and percentage of lipids (Hammond et al. , 2000), which suggested the possibility of the transmission of scabies mites from humans to dogs. Compared with the other three hosts, rabbits have the shortest generation time (Table S13 ) and are more susceptible to scabies mites. According to the statement of local farm workers, we also learned that humans who come in contact with rabbit mites experience intensive itching symptoms; however, because humans generally apply drugs before the mites settle down on the skin, we do not know if rabbit mites can establish a permanent infection on humans or vice versa. The condition of pigs living with rabbits is very rare, thus few reports have been published about the cross-infestivity between pig mites and rabbit mite. The results of the pairwise selective sweeping analysis provided clues to investigate cross-infestivity. Except in humans, it is feasible to investigate the genetic basis of cross-infestivity by performing artificial infection experiments to test cross-infestivity and differentially expressed genes during host shift. ­