3.5 Strong selective sweep signals provided clues to the genetic basis of variant divergence and cross-infestivity
Scanning electron microscopy and light microscopy showed that S. scabiei lives in the skin stratum corneum reside at the interface of stratum lucidum and stratum granulosum (Estes et al. , 1983; Neste & Lachapelle, 1981; Van Neste, 1984). As shown inTable S20 , the epidermis of humans, pigs, dogs and rabbits are 46.9 ± 2.3 μm, 65.8 ± 1.8 μm, 18.94 ± 2.29 μm, and 17.0 ± 1.2 μm thick, respectively (Bhandal et al. , 2012; Bronaugh et al. , 1982; Nicoli et al. , 2008), while the stratum corneum of them are 16.8±0.7 μm, 26.4±0.4 μm, NA and 11.7±0.5 μm. According to the results of PSMC, humans, pigs, dogs and rabbits get infected with scabies mites for more than 30 kyr ago, to reveal the potential genome footprint that may left by a couple of hundred thousand years co-evolution of the scabies mites and the hosts, we used FST & θπ to find possible selection sweeping signal between any of the two hosts. As shown in Figure 5, strong selective signals were observed between pig mites and human mites: about 10 times as many genomic regions with strong selective sweep signals in pig mites (3.84% of the genome, containing 358 genes) as there are in human mites (0.40% of the genome, containing 37 genes), with significant enrichment in “cysteine-type peptidase activity (10 genes), Neuroactive ligand-receptor interaction (18 genes), and Apoptosis (11 genes) (Table S21 ).There are three times as many genomic regions with strong selective sweep signals in dog mites (0.81% of the genome, containing 77 genes) as there are in human mites (0.27% of the genome, containing 25 genes), with high enrichment in “cysteine-type peptidase activity (five genes) and apoptosis (five genes)(Table S21 ). As shown in Table S22-24 , the involved genes mainly including Sar s 1 allergen SMIPP-C (Peptidase C1A, papain C-terminal) and group 3 allergen SMIPP-S (Peptidase S1). However, as a recently emerging mite variant, rabbit scabies mites showed very limited selective sweeping signals compared with mites from any of the other three hosts (Table S21 ), especially with human mites and dog mites, which might be the explanation of cross-infestivity between rabbits and the other three hosts.
Discussion
Genome assembly and evolution
Scabies mites represent a highly contagious ectoparasite that can affect more than 100 mammal species (Escobaret al. , 2021). In this study, we presented the chromosome-scale genome assembly for ectoparasite S. scabiei . To the best of our knowledge, this is the first chromosome-level genome of all mite species to be determined to date (Table 1 ), providing a reference genome for comparative genomics of mite biology and further study of scabies mite.
Genome evolution results showed that scabies mites from four hosts clustering together, and rabbit mite is closer to human mites followed by pig mites and dog mites. However, the population genetics results indicated the clear cluster was defined by hosts, and rabbit mites seems distantly related with other mites, providing evidence supporting the hypothesis that S. scabiei is not a single panmictic population and genetic subdivisions occurs according to the hosts (Alasaad et al. , 2011; Walton et al. , 2004). It thus can be concluded that S. scabiei from various hosts are genetically similar to each other and are likely variants of one species that mainly clustered by host species.
If the variants classified by hosts is the case, is there any order of infection time for mites from these hosts? Surprisingly, the origin time of human mites support the current scientific consensus that humans are the principal host for Sarcoptes mites. Domestication of dogs can be traced back to at least around 15,000 years, and possibly earlier, being domesticated from the gray wolf in East Asia around 100,000 years ago (Bardeleben et al. , 2005; Currier et al. , 2011; Savolainen et al. , 2002; Wayne et al. , 1997); moreover, recent studies have shown that, in southern East Asia, the groups of dogs and wolves began to diverge about 33,000 years ago (Skoglund et al. , 2015; Wang et al. , 2016; Wang et al. , 2013). The estimated origin time of dogs (about 37 kyr - 61 kyr) all fall within the time frame of human domestication of domestic dogs (15,000 years to 100,000 years ago), indicating that the canine-derived scabies mites may have come from human-derived scabies mites. However, the results showed that pigs and rabbits get infected with scabies mites long before they were domesticated by humans, contradicting the hypothesis that humans transmitted scabies mites to animals through domestication activity (Currier et al. , 2011a; Friedman, 1936). The possible transfer of human-derived mites to dogs probably reflected the intimate relationship of humans and dogs.