DISCUSSION
InDel mutations related to economic traits have been investigated in domestic animals such as pigs (Jung et al., 2020; Zhang et al., 2019), cattle (Zhou et al., 2019; Xu et al., 2018), and sheep (Wu et al., 2020; Zhao et al., 2018), indicating that InDel has a non-negligible role in animal breeding. In this study, various candidate genes for economic traits and adaptive traits of animals have been identified. In particular, 94 candidate genes were found to be related to muscle development (such as MEF2C , TCF4 , MAPK14 , andDDX17 ).
Myocyte enhancer factor 2C (MEF2C ) is widely involved in the development of heart and skeletal muscle during the embryonic stage. The synergistic action between MEF2C and the MYoD family factors promote the development of skeletal muscle during the embryonic process, and MEF2C can regulate cell proliferation by acting as the endpoint of the intracellular signaling pathway regulated by various growth factors (Black et al., 1998). MEF2C also exhibits DNA binding activity in muscles and is highly expressed in muscle cells during embryonic formation to regulate muscle development and differentiation by interacting with muscle-derived bHLH protein, thyroid hormone receptor, PEA3 , and PDP1 (Pozarska et al., 2016). As a marker of muscle connective tissue fibroblasts, transcription factor 4 (TCF4 ) can regulate the development of slow and fast muscles and promote the conversion of fetuses to adult muscles (Mathew et al., 2011). Tumor protein p73 (TP73 ) is involved in the regulation of cell apoptosis (Stiewe et al., 2001), polyciliogenesis (Fujitani et al., 2017), germ cell maturation (Santos et al., 2018), and multiple biological processes (Nemajerova et al., 2019). Thus,TP73 plays an important role in animal development and homeostasis maintenance.
DEAD box RNA helicase 17 (DEAD-box helicase 17, DDX17 ) regulates gene expression and transcription factor activity (Bourgeois et al., 2016). DDX17 is an activator of MyOD , which regulates skeletal muscle development (Legerlotz et al., 2008). DDX17knockdown hinders skeletal muscle development and differentiation (Caretti et al., 2006). Mitogen-activated protein kinase 14 (MAPK14 ) belongs to the MAP kinase family and is an important factor in biological development. MAPK14 promotes cell proliferation and activation by inhibiting the differentiation of vascular smooth muscles during vascular injury. Pro-inflammatory gene expression participates in the repair of blood vessels (Wu et al., 2019). In addition, MAPK14 is involved in muscle atrophy by direct phosphorylating and activating Bcl-2 family member Bax via mitochondrial-dependent pathway, thus resulting in muscle fiber death (Wissing et al., 2014).
This work also screened many candidate genes related to germ cell development and reproductive hormone regulation, such as SRD5A1 ,FBXW11 , DMRT1 , CXADR , and RPTOR . Early studies have isolated steroid 5 alpha-reductase 1 (SRD5A1 ) from rat liver and found that it is one of the three forms of steroid 5α-reductase (Russell et al., 1994). SRD5A1 is involved in the metabolism of estrogen and androgen. The catalytic substrates ofSRD5A1 include testosterone, progesterone, androstenedione, epinephrine -T, cortisol, aldosterone, and deoxycorticosterone. This enzyme catalyzes the conversion of testosterone into stronger androgen: 5α-di hydrotestosterone (DHT ). Therefore, SRD5A1 plays an important role in mammalian stress, immune system regulation, and reproduction (Han et al., 2021). F-box and WD repeat domain containing 11 (FBXW11 ), a member of the F-box protein family and a part of the ubiquitin ligase complex, is important in the regulation of ubiquitin-dependent spermatogenesis. The mRNA level of FBXW11 is positively correlated with sperm motility (Liu et al., 2021).
Double sex and mab-3 related transcription factor 1 (DMRT1 ) is involved in the sex determination of vertebrates. The functional lack ofDMRT1 in mice can lead to excessive proliferation of sertoli cells without further differentiation in the testis, leading to germ cell loss (Raymond et al., 2000). Knocking out the DMRT1 in the sertoli cells in mice will activate FOXL2 , which in turn causes the Sertoli cells to be reprogrammed into granular cells and the testicular tissue to transform into an ovarian-like morphology (Matson et al., 2011). As a member of the adhesion receptor tight junction protein family, CXADR Ig-like cell adhesion molecule (CXADR ) plays an important role in embryonic development. Its absence causes embryonic development to stagnate in morula (Kwon et al., 2015). Regulatory associated protein of MTOR complex 1 (RPTOR ) encodes the MTOR complex regulatory-related protein and is a part of the mTORC1 complex, which is important in the maintenance and renewal of mouse spermatogonia (Serra et al., 2019).
Some candidate genes related to immune regulation were also identified. CD200 molecule (CD200 ) is widely distributed on the surface of myeloid immune cells, such as thymocytes, B cells, and macrophages (Barclay et al., 1981). CD20 0 can combine with CD200R to participate in immune regulation. The CD200 knockout in mice increases the activity of macrophages and cell lineage and disrupts the immune balance of body (Hoek et al., 2000). Serum/glucocorticoid regulated kinase 1 (SGK1 ) plays an important role in cellular stress response. SGK1 mediates the regulation of glucocorticoid hormone and inhibits the proliferation of progenitor cells by increasing glucocorticoid hormone receptor phosphorylation (Anacker et al., 2013). Interleukin 17 receptor B (IL17RB ) exhibits immunomodulatory activity, and its expression is up-regulated in patients with rhinitis (Matsumoto et al., 2011). IL17RB also participates in the regulation of inflammatory response by mediating NF-kappa B activation and IL8 production (Ruskin et al., 2012).
In this study, many genes related to metabolism were observed (e.g.,INSR, STXBP3, H6PD, and APOE ). Insulin regulates the body’s glucose, protein, and fat homeostasis. As the insulin receptor,INSR participates in insulin signaling pathway (Mukherjee et al., 2009). When the INSR gene is knocked down, insulin cannot perform function normally in the liver of mice, thus leading to the gradual deterioration of liver function (Okamoto et al., 2005). Variations inINSR cause insulin resistance syndrome and Donohue syndrome in multiple species (Reaven et al., 2005). The combination betweenSTXBP3 (syntaxin binding protein 3) and syntaxin 4 regulates insulin in peripheral tissues (Jewell et al., 2010). Mice withSTXBP3 homozygous knockout cannot survive, whereas those withSTXBP3 heterozygous knockout exhibit reduced insulin secretion and gradually become glucose intolerant when fed with a high-calorie diet rich in fat and carbohydrates (Oh et al. 2005). Hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase (H6PD ) is involved in cell biochemical reactions and can mediate the regeneration of glucocorticoids (Zhang et al., 2009). H6PD knockout in mice reduces their sensitivity to glucocorticoids, which in turn increases insulin sensitivity and glucose uptake in muscles, thus eventually leading to severe skeletal myopathy (Lavery et al., 2008). Apolipoprotein E (APOE ) encodes apolipoprotein and is one of the transport carriers of chylomicrons. APOE mediates lipoprotein catabolism and promotes the hydrolysis and clearance of soluble Aβ protein (Jiang et al., 2008). Its abnormalities lead to endothelial cell atherosclerosis (Nakashima et al., 1998) and central nervous system defects (Masliah et al., 1995).