3.2 Evolution of the scabies mite genome
To determine the evolution of the scabies mite genome in the context of the Chelicerata, we collected seven other arthropods and a nematode as outgroup for phylogeny analysis. A total of 15,542 gene families and 1,338 shared high confidence single-copy orthologous genes (Figure S5 ) were identified. The phylogenetic tree resulted in a well-supported phylogeny (Figure 2a ): scabies mite and spider mite clustered together (Acariformes), while Tropilaelaps mite, predatory mite, and black-legged tick clustered together (Parasitiformes) and formed a separate group with Stegodyphus mimosarum. Based on this phylogenetic tree, we estimated that S. scabiei and Tetranychus urticae separated at approximately 338.8 Mya (Figure 2a ), which indicated a relatively distant relationship between these two species. To further understand the phylogenetic relationship of scabies mites from various hosts, we used protein-coding single‑copy orthologous genes of scabies mites from four hosts, as well as free-living mite Dermatophagoides pteronyssinus and parasitic mite Psoroptes ovis . This result showed thatS. scabiei isolated from rabbits is genetically similar toS. scabiei isolated from humans, and then with pigs and dogs, followed by the free‑living dust mite and the surface living scab mite, but distantly related to the spider mite (T. urticae ) (Figure 2b ). The phylogeny structure supported the previous study that the subclass Acari is diphyletic, with the superorders Acariformes (scabies mite and spider mite) and Parasitiformes (Tropilaelaps mite and predatory mite) being distantly related (Gu et al. , 2014; Hoy et al. , 2016). As only colonies from one individual animal and one geographical location were used for one host species, whether scabies mites from individual animals have any intrinsic relationship remains unknown. Thus, we are wondering that the so called “variants” more reasonable to be classified by host species or geographical locations?
To answer these questions, we expanded the sample size to 20 including four host species (humans, dogs, pigs and rabbits) and three geographical locations (China, Australia and America) (Table S1; Figure S6 ). Genome alignment indicated a mapping rate of 82.74–98.09% and ~40-fold depth for each individual relative to our rabbit mite reference genome (Table S11) . After single nucleotide polymorphism (SNP) calling (Table S12 ), we examined the correlation between host species and geographical locations. The results showed that, although extremely similar genetic diversities were observed among these populations, both principal components analysis (PCA) consistently supported four distinct groups according to the host species (Figure 2c ). Specifically, rabbit mites seem to be relatively distinct with mites from other three host species. Varying the number of presumed ancestral populations (K ) from two to four, we found that rabbit mites remain distinct with mites from other three hosts (Figure S7 ). Interestingly, mites from humans and dogs cluster together, which may reflect the intimate relationship of these two hosts and indicated potential transmission between each other.
Although no direct evidence reported, the current scientific community believed that humans are the primary host of scabies mites, and other animals get infected from humans during the domestication (Currier et al. , 2011). To provide clues for the origin and transmission of scabies mites, PSMC was used and the results revealed a varied demographic history from over 100 kyr (1,000 years) to 10 kyr ago (Figure 2d ), a period significantly younger than any of the currently reported fossil mites, including a nearly modern looking fossil oribatid mite (order Acariformes) that existed in the Devonian (late Paleozoic) period at ~380 mya (million years ago)(Norton et al. , 1988), and the earliest fossil Astigmata mites at ~28 mya (Petrunkevitch & Alexander, 1952). For human mites, the origin time is around 100 kyr ago (Figure 2d ), nearly the same time with the emerging of the modern humans (Fenner, 2010; Hu et al. , 2017), supporting that humans are the primary host of scabies mites (Currier et al. , 2011b). However, for mites from other hosts, the origin time of these mites is far earlier than their hosts were domesticated by humans. To be specific, pigs, dogs, and rabbits became infected with mites at around 100 kyr, 61 kyr, and 45 kyr ago, while these hosts were domesticated at around 10 kyr, 15 kyr, and 1.5 kyr ago (Figure 2d; Table S13 ). We also noticed that the effective population size of rabbit mites is significantly larger than mites from any of the other three hosts, which may reflect the parasite load of these hosts.