In this study, we compared the genomes of 27 Xinjiang Mongolian cattle (20 resequenced and seven publicly available genomes) to the 129 genomes of nine representative breeds worldwide. Our exploration of the cattle variome and selective signals focused specifically on genomic diversity, breed origin, and candidate selected genes responsible for the adaptation to the desert environment in Xinjiang Mongolian cattle.
Compared with other Bos taurus breeds, our Xinjiang Mongolian cattle have the highest nucleotide diversity associated with the lower inbreeding coefficient, the lowest linkage disequilibrium, and the highest effective population size (except for Hanwoo cattle between generations ago of 54 and 454). This unique diversity pattern could be influenced by certain historical demography such as hybridisation with or introgression from different bovine species or subspecies. In addition, we also observed the highest nucleotide diversity of Bos indicus with lower artificial selection or introgression from different bovine species [8], the faster LD decay of commercial European taurine with stronger artificial selection suggested by the highest inbreeding coefficient [4] and the lowest nucleotide diversity of African Muturu cattle [27].
The findings from the PCA and NJ tree indicate that the Xinjiang Mongolian cattle can be classified within the Bos taurus cluster. Additionally, the estimation of ancestry and the construction of a phylogeny considering potential migration events suggest the occurrence of gene flow from Bos indicus into the Xinjiang Mongolian cattle population. This observation is supported by the lowest level of genetic differentiation observed in the Xinjiang Mongolian cattle when compared to the relationships between Bos taurus populations and Bos indicus. The aforementioned findings may provide an explanation for the notably high nucleotide diversity observed in Xinjiang Mongolian cattle within the Bos taurus species.
The most crucial attribute of Xinjiang Mongolian cattle is their adaptability to the desert environment. The identification of candidate genes under selection is of significant importance in elucidating the genetic basis underlying the well-adapted characteristics of Xinjiang Mongolian cattle residing in desert environments. Among the candidate selected genes identified by two or three approaches, functional enrichment analysis showed the most significance of oxidoreductase activity, consisting of four genes of the cytochrome P450 family 2, subfamily J. The cytochrome P450 enzymes, a type of monooxygenase with a prosthetic group of heme-iron, are involved in the metabolism of arachidonic acid, the secretion of the final metabolites in urine or bile, and the transformation of a potent vasodilator of renal preglomerular vessels stimulating water reabsorption [28]. Among these families, the CYP2J2 activity has been demonstrated to be regulated by high-salt diet [29]. It is noteworthy that in camel whose most distinctive feature is the adaptation to the desert environment, the number of the copies of CYP2J is higher than that in cattle, horse and human [30–32]. The above findings indicate that CYP2J subfamily genes may be important factors in the adaptation of Xinjiang Mongolian cattle to the desert environment.
As has been said, kidneys play a major role in the process of water reabsorption through increasing the osmolarity of urine. We surveyed published literature and identified several selected genes associated with the kidney or urinary system. PDE11A gene along with extreme π ratio and XP-EHH encodes a dual-specificity phosphodiesterase and is expressed in adrenal cortex. It has been reported that a germline mutation at PDE11A locus is associated with adrenocortical hyperplasia in human [33]. DIS3L2 gene also along with extreme π ratio and XP-EHH, encodes an exoribonuclease, and its germline mutations caused the Perlman syndrome with kidney abnormalities [34]. Among the selection candidates in our list are SLIT2 (a ligand in ureteric bud and metanephric mesenchyme) in which the mutations confer for congenital anomalies of the kidney and urinary tract in human [35], KCNIP4 a potassium channel–interacting protein whose translocation implicates renal cell cancer [36], OSGEP enabling N(6)-L-threonylcarbamoyladenine synthase activity and metal ion binding activity and associated with a renal defect manifesting in proteinuria and hypomagnesemia [37], CLIC4 a cytosolic protein in which null mouse embryos exhibit impaired renal tubulogenesis [38], FGF10 a multifunctional FGF family member implicated renal ischemia/reperfusion injury [39] and ureter and kidney development [40], and PKHD1 a large transmembrane protein fibrocystin involved in polycystic kidney disease [41]. Notably, the GO term of branching morphogenesis of an epithelial tube (PKHD1, CLIC4, SLIT2, FGF10) was enriched, which is critical to ureteric bud formation and epithelial branching during kidney development [42]. Moreover, the enrichment analysis also showed three GO terms (including three genes LOC617141, LOC112442378, LOC527385) associated with transmembrane transporter activity involved in osmoregulation in the renal medulla in camel [43]. In addition, an overrepresentation of categories associated with iron ion and heme binding was also detected, including six genes (TPH1, FECH, LOC107132327, LOC521656, LOC530929, LOC511936). In fact, similar GO terms were also detected in enrichment analysis of differentially expressed genes between water-restricted and normal condition in renal cortical and medullary of bactrian camel [43]. Similarly, an excellent study also revealed several selected genes related to renal vasodilation, ion transmembrane transport, water-salt metabolism, and bicarbonate absorption in Taklimakan Desert sheep [44]. From the above results, we can conclude that these genes could have been affected by selection targeting at water reabsorption and osmoregulation during the adaptation to desert environment.
The scarcity of food in desert environments presents a secondary barrier to adaptation, hence emphasizing the significance of energy and metabolism. The second-ranked GO term identified by enrichment analysis is ATPase binding, which is related to catalyze the hydrolysis of ATP, a key player in biological energy capture and use, including five genes (NCSTN, PEX19, PDE4D, TOR1AIP2, TOR1AIP1). The third-ranked GO term is NAD + ADP-ribosyltransferase activity involved in cellular energy levels [45], including four genes (ART1, PARP6, PARP2, LOC407145). Moreover, four of the top 10 KEGG pathways identified by enrichment analysis are related to metabolism, and one of them is arachidonic acid metabolism which is also implicated in adaptation to desert environments in camel and sheep [32, 44], including four genes (LOC107132327, LOC521656, LOC530929, LOC511936). Therefore, we could speculate that these genes, GO terms, or pathways may play a role in metabolic regulation and energy balance in desert environment adaptations.
For animals living in extreme environments, small body size could help overcome the challenge of scarce food supply by virtue of lower metabolic requirement and less energy consumption [44, 46]. After reviewing published literature on candidate selected genes, a total of five genes were found to be associated with body size traits. One interesting observation was the presence of PPARGC1A with strong signal of selection. PPARGC1A encodes a transcriptional coactivator that regulates the genes involved in energy metabolism and plays an important role in insulin signaling, mitochondrial regulation and adaptive thermogenesis [47–49]. Its mutations have been reported to be associated with body mass index in human [50]. Another candidate gene is NPPC, a natriuretic peptide that regulates endochondral ossification of the cartilaginous selected growth plate, in which SNP markers are associated with human height [51]. Other noteworthy genes in our candidate list were APPL2, an adiponectin receptor associated with overweight and obesity in a Chinese population [52], DOCK5, a susceptibility gene for severe obesity [53], and SLC30A8, a zinc efflux transporter implicated in type 2 diabetes and obesity in Asians [54]. All the above findings indicate that these genes are strong candidates contributing to the small body size responsible for adaptation to desert environments in Xinjiang Mongolian cattle.