Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
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Jing Pan
Abstract
The Mongolian horses have excellent endurance and stress resistance to adapt to the cold and harsh plateau conditions. Intraspecific genetic diversity is mainly embodied in various genetic advantages of different branches of the Mongolian horse. Since people pay progressive attention to the athletic performance of horse, we expect to guide the exercise-oriented breeding of horses through genomics research. We obtained the clean data of 630,535,376,400 bp through the entire genome second-generation sequencing for the whole blood of four Abaga horses and ten Wushen horses. Based on the data analysis of single nucleotide polymorphism, we severally detected that 479 and 943 positively selected genes, particularly exercise related, were mainly enriched on equine chromosome 4 in Abaga horses and Wushen horses, which implied that chromosome 4 may be associated with the evolution of the Mongolian horse and athletic performance. Four hundred and forty genes of positive selection were enriched in 12 exercise-related pathways and narrowed in 21 exercise-related genes in Abaga horse, which were distinguished from Wushen horse. So, we speculated that the Abaga horse may have oriented genes for the motorial mechanism and 21 exercise-related genes also provided a molecular genetic basis for exercise-directed breeding of the Mongolian horse.
1 Introduction
As an ancient breed, the Mongolian horse has gone through a long breeding period [1]. With a view to research tendentiousness, researchers pay more attention to traits of Thoroughbred horse [2–4] and Quarter horse [5,6], but not the Mongolian horse and its diverse sub-branch. The preeminent endurance and stress-resistance of Mongolia horses are important factors for them to well adapt to the cold and harsh plateau environment [7]. Natural factors may have enormous impacts on evolution owing to the rough domestication of the Mongolian horse [8]. Due to various geographic conditions and human necessities, the Mongolian horse gradually formed several specific traits. Some horses which adapt to the desert climate have larger feet, for instance, some horses which adjust to a mountain road with rocks have supple body and hard hoofs; in addition, the features of a horse which accommodate to the grassland climate have tall physique and are good at running [9]. Living in the Xilin Gol grassland of Inner Mongolia, the Abaga horse belongs to the steppe horse and speeds up to 1,600 m every 91.47 s [1]. Wushen horse, which is small build and has broad-flat horseshoe, as symbol of the desert horse in the south of Maowusu desert of Ordos City in Inner Mongolia, can hoof steadily in the desert, albeit not fast at a running speed of 13–15 km/h [10].
In Mongolia, the herdsmen depend on horses for reasons that they are the indispensable sources of pastoral rations, such as meat and dairy products, and used to be one of the means of transport by herders [8]. Furthermore, the Mongolian horse was an essential and distinguished war horse in history [11]. For the Naadam of traditional festivals in Mongolia, horse racing is one of the entertaining activities for herds and is regarded as the second most popular sporting event after wrestling [12]. So, the running speed of Mongolian horses has been one of the focus of attention. Despite not being the fastest horse in the world, people still endeavor to improve the running speed of the Mongolian horse through unremitting consideration and breeding.
To discuss the genetic variation between Abaga horse and Wushen horse in Mongolian horse strains, we planned to analyze data of the entire genome with second-generation sequencing technology to seek out exercise-related single nucleotide polymorphism (SNP) locus of Mongolian horse and offer a reference for identification and improvement of Mongolian horse varieties.
2 Materials and methods
2.1 Experimental animals and sample preparation
We selected four healthy Abaga horses (two female and two male) of 1-year-old in the Inner Mongolia Abaga County and ten good-conditioned Wushen horses (eight female and two male) at age of 4–6 in the Inner Mongolia Ordos City Wushen County. We collected the jugular blood of animals. Adhering to the manufacturer’s instructions for the extraction of DNA from the whole blood, the genome was extracted by the AxyPrep blood genomic DNA kit. Then we used the NanoDrop 1000 spectrophotometer and polyacrylamide gel electrophoresis to detect the concentration and integrity of the genome. The concentration of extracted DNA was between 26.4 and 34.4 ng/μL for subsequent library construction.
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Ethical approval: The research related to animal use has been complied with all the relevant national regulations and institutional policies for the care and use of animals. Procedures involving animals and their care were conducted in conformity with Guidelines on the Humane Treatment of Laboratory Animals (HTLA Pub. Chapter 2–6, revised 2006 in China) and were approved by the Animal Care and Use Committee of the Inner Mongolia Agricultural University.
2.2 Library preparation and whole-genome sequencing
A TruSeq DNA Sample Prep Kit was used to construct a sequencing library. Whole-genome sequencing of the horses was performed using the Illumina HiSeq X Ten Sequencing System.
2.3 Data quality control and comparison to reference genome
The raw data of 639,723,611,100 bp were sequenced from 14 samples. The inferior quality reads which have sequencing adapter, higher than 10% of N (base of uncertainty) content or inferior mass base (Q ≤ 5) content of higher than 50% were filtered out by in-house Perl/Python scripts to achieve clean data of 630,535,376,400 bp. The Q20, Q30, error rate, GC content, and other information on these data were counted by in-house Perl/Python scripts. The sequencing reads were mapped to reference genomes (Ensembl release 82) by BWAmem (bwa-0.7.8) [13], and polymerase chain reaction (PCR) and optical repetition of results were removed by using Picard [14]. Statistics of mapping rate, average depth, and coverage of the data after comparison were computed by in-house Perl/Python scripts.
2.4 SNP calling and annotation
SNP calling was performed using the GATK HaplotypeCaller (v3.5) [15]. To evaluate the reliability of the detected SNP sites and filter inferior quality SNP, we used SAMTools for SNP detection [16]. Simultaneously, the dbSNP database of 5,019,393 SNPs and 670K chip site information were downloaded. The data were used as the training set, and the detected SNPs were evaluated and filtered by using the GATK VQSR process. The standard for the retention of the final site is the tranche value of 99 (Ti/Tv = 2.02). Finally, the SNPs of equine population were filtered: GQ > 10, MAF > 0.05, and call rate > 0.9. The variants after filtering were annotated by ANNOVAR (v2016-02-01) [17].
2.5 Selective sweep analysis
To identify potential selective sweeps between Abaga horse (fast) and Wushen horse (slow), Pi log2(slow/fast) and F-statistics (FST) were calculated together using VCFtools with a 20 kb sliding window and a step size of 10 kb. Windows that contained less than ten SNPs were excluded from further analysis. The windows that were simultaneously (1) in the top 5% of Z-transformed FST values and (2) in the bottom 5% Pi log2(slow/fast) were considered to be candidate selective regions in Abaga horse. The same applies to the Wushen horse.
2.6 Statistics and advanced analysis of positively selected and candidate genes
We annotated the positively selected genes via gene ontology (GO; GOseq) to further screen out the major enriched functions [18]. The pathways which included these selected genes were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG; KOBAS) [19]. Many positively selected genes which are in the Abaga horse were analyzed further without the overlapped genes between the Abaga horse and Wushen horse.
3 Results
3.1 Related-clean data stated
We performed the entire genome second-generation sequencing for the whole blood of four Abaga horses and ten Wushen horses with the Illumina HiSeq X Ten sequencing platform. The clean data of 630,535,376,400 bp (effective rate of data: 98.56%, error rate of data: 0.03%, mean of Q20: 94.95%, and mean of Q30: 89.80%) were sequenced by filtration and 41.95G as the mean of clean data was generated in each sample (Table 1). Then, the data were mapped to the reference genome (Ensembl release 82) via BWAmem [13]. Without PCR and optical repetition, the successful mapping rate of data was 98.36%. For the 14 samples, the average sequencing depth was 16.75 × coverage and the average cover degree was 99.55% on reference sequences (Table 2).
Data quality control
Sample | Sample type | Raw data | Clean data | Effective (%) | Error rate (%) | Q20 | Q30 | GC content (%) |
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AB01 | Abaga Horse | 48,216,007,500 | 47,152,467,900 | 97.79 | 0.03 | 96.21 | 92.24 | 42.89 |
AB02 | Abaga Horse | 43,047,445,800 | 42,340,444,800 | 98.36 | 0.03 | 96.17 | 92.1 | 42.65 |
AB03 | Abaga Horse | 47,273,694,300 | 46,714,855,800 | 98.82 | 0.03 | 95.76 | 91.36 | 42.55 |
AB04 | Abaga Horse | 48,416,284,200 | 47,906,212,800 | 98.95 | 0.03 | 95.96 | 91.47 | 42.13 |
WS01 | Wushen Horse | 49,415,626,200 | 48,784,894,800 | 98.72 | 0.03 | 95.69 | 91.23 | 41.97 |
WS02 | Wushen Horse | 53,074,008,900 | 52,417,962,000 | 98.76 | 0.03 | 96.09 | 92.19 | 42.35 |
WS03 | Wushen Horse | 45,358,642,200 | 44,789,835,900 | 98.75 | 0.03 | 95.87 | 91.47 | 41.97 |
WS04 | Wushen Horse | 47,681,665,800 | 47,139,254,400 | 98.86 | 0.03 | 95.94 | 91.6 | 41.66 |
WS05 | Wushen Horse | 50,647,742,700 | 50,012,300,700 | 98.75 | 0.03 | 95.86 | 91.47 | 41.84 |
WS06 | Wushen Horse | 45,072,226,800 | 44,633,740,200 | 99.03 | 0.03 | 95.79 | 91.61 | 42.19 |
WS07 | Wushen Horse | 34,681,049,100 | 34,040,596,500 | 98.15 | 0.05 | 92.2 | 84.65 | 43.07 |
WS08 | Wushen Horse | 45,212,322,600 | 44,350,535,700 | 98.09 | 0.04 | 92.41 | 84.97 | 43.02 |
WS09 | Wushen Horse | 44,382,563,100 | 43,593,247,800 | 98.22 | 0.04 | 92.47 | 85.07 | 43.23 |
WS10 | Wushen Horse | 37,244,331,900 | 36,659,027,100 | 98.43 | 0.04 | 92.91 | 85.77 | 43.12 |
Average | 45,694,543,650 | 45,038,241,171 | 0.03 | 94.95 | 89.80 | 42.47 | ||
Total | 639,723,611,100 | 630,535,376,400 | 98.56% |
Data comparison
Sample | Total reads | Mapping rate (%) | Average depth | Coverage at least 1× (%) | Coverage at least 4× (%) | Coverage at least 10× (%) |
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AB01 | 315,216,417 | 98.55 | 17.46 | 99.59 | 99.32 | 93.57 |
AB02 | 282,990,429 | 98.49 | 15.82 | 99.56 | 99.24 | 89.18 |
AB03 | 312,280,472 | 98.49 | 16.93 | 99.52 | 98.98 | 90.17 |
AB04 | 320,340,217 | 98.22 | 18.25 | 99.57 | 99.15 | 93.1 |
WS01 | 326,298,749 | 98.6 | 17.63 | 99.54 | 99.25 | 94.36 |
WS02 | 350,423,462 | 98.41 | 19.65 | 99.57 | 99.24 | 94.72 |
WS03 | 299,507,485 | 98.63 | 16.45 | 99.51 | 99.16 | 92.2 |
WS04 | 315,038,236 | 98.52 | 17.28 | 99.51 | 98.98 | 91.77 |
WS05 | 334,519,623 | 98.65 | 18.19 | 99.54 | 99.24 | 95.43 |
WS06 | 298,331,035 | 98.52 | 16.88 | 99.53 | 99.23 | 92.89 |
WS07 | 227,540,381 | 97.88 | 12.85 | 99.56 | 98.73 | 68.52 |
WS08 | 296,433,759 | 97.97 | 16.75 | 99.61 | 99.32 | 90.53 |
WS09 | 291,390,679 | 98 | 16.44 | 99.51 | 99.18 | 88.97 |
WS10 | 245,088,985 | 98.13 | 13.85 | 99.6 | 99.05 | 76.55 |
Average | 301099994.9 | 98.36142857 | 16.745 | 99.55142857 | 99.14785714 | 89.42571429 |
3.2 Distribution of positive selection genes on chromosomes
Based on the data of SNP following SNP calling (Figure 1), we obtained the genes of significant genetic differences by using FST between Abaga horses and Wushen horses and narrowed the above genes down to 479 and 943 positively selected genes combined with SNP polymorphism analysis in Abaga horses and Wushen horses, respectively (Figure 2). We discovered that these selected genes were mainly distributed on chromosomes 4, 7, and 10 in Abaga horses, and on chromosomes 1, 4, 8, and 16 in Wushen horses with a analysis of genes distribution on the chromosome (Figure 3).

SNP following SNP calling. High quality SNPs were evaluated and identified. AB and WS indicate Abaga horse and Wushen horse, respectively.

Identification of selected regions in Abaga horse and Wushen horse. (a) To identify potential selective sweeps between Abaga horse (fast) and Wushen horse (slow), log2(πslow/πfast) and FST were calculated together using VCFtools with a 20 kb sliding window and a step size of 10 kb. Windows that contained less than ten SNPs were excluded from further analysis. The windows that were simultaneously (1) in the top 5% of Z-transformed FST values and (2) in the bottom 5% log2(πfast/πslow) were considered to be candidates selective regions in Abaga horse. (b) The same applies to the Wushen horse.

Distribution of selected genes on chromosomes.
3.3 GO, KEGG pathways, and exercise-related genes
The above positively selected genes were functional annotations by GO. The selected 479 genes of Abaga horse were mainly enriched in neuron part (GO:0097458), neuron projection (GO:0043005), regulation of membrane potential (GO:0045838), positive regulation of cell projection organization (GO:0031346), neuron–neuron synaptic transmission (GO:0007270), synaptic transmission, glutamatergic (GO:0035249), neurotransmitter secretion (GO:0007269), antigen processing and presentation (GO:0019882), telencephalon cell migration (GO:0022029), and forebrain cell migration (GO:0021885). The selected 943 genes of the Wushen horse were mainly enriched in membrane part (GO:0044425), an intrinsic component of membrane (GO:0031224), an integral component of membrane (GO:0016021), cell projection (GO:0042995), neuron part (GO:0097458), neuron projection (GO:0043005), synapse (GO:0045202), cilium (GO:0005929), and cell projection assembly (GO:0030031) (Figure 4).

Function analysis based on GO: (a) the most enriched GO terms in Abaga horse and (b) the most enriched GO terms in Wushen horse.
By pathways enrichment analysis of KEGG with the positively selected 479 genes in Abaga horse and 943 genes in Wushen horse, the enriched pathways (P ≤ 0.05) of Abaga horse included propanoate metabolism, viral myocarditis, phototransduction, PI3K-Akt signaling pathway, glycerolipid metabolism, morphine addiction, and mRNA surveillance pathway in which the pathway with the largest number of enriched genes (13 genes) was PI3K-Akt signaling pathway. Besides that, the enriched pathways (P ≤ 0.05) of the Wushen horse contained base excision repair, glutamatergic synapse, endometrial cancer, glycolysis/gluconeogenesis, propanoate metabolism, and ABC transporters (Figure 5).

The KEGG pathway enrichment analysis: (a) top 20 of enriched pathways by statistics in Abaga horse and (b) top 20 enriched pathways by statistics in Wushen horse.
Further on SNPs, we analyzed the functions of 440 genes of Abaga horse without the 39 overlapped genes of positively selected genes between the Abaga horse and Wushen horse. We focused on the enriched exercise-related pathways which are referred to as metabolic pathways [20], Ras signaling pathway [21,22], PI3K-Akt signaling pathway [21,23–28], MAPK signaling pathway [29], Hippo signaling pathway [30], valine, leucine, and isoleucine degradation [31], cardiac muscle contraction [32], NF-kappa B signaling pathway [33], arachidonic acid metabolism [20], regulation of actin cytoskeleton [20,29], insulin signaling pathway [2,20], and fatty acid metabolism [2,20] in the 440 positively selected genes of Abaga horse that distinguished from the Wushen horse (Figure 6). These enriched pathways comprised some recurrent genes (Figure 6). Taking repeated genes as pivots, we speculated that the synergistic effect of pathways enabled a faster running speed of the Abaga horse compared with the Wushen horse.

The exercise-related candidate genes and pathways of Abaga horse.
According to the analysis of GO, KEGG, and individual gene function, we subsequently put our interest in the exercise-related genes of the Abaga horse. Twenty-one genes may involve in exercise of Abaga horse while their functions embodied vasoconstriction (HTR2B) [34,35], angiogenesis (CDH5) [36], cardiac contraction (KCNQ1) [37–39], cardiac development and muscle structure (ENAH) [40,41], muscle growth (PIH1D1, SMURF1) [42–44], myogenic differentiation (UNC13C) [[45,46], skeletal muscle function (ATP1A3) [47,48], femur strength and bone mineral density (PPP2R5B, PPP6R3) [49,50], osteoclast growth (PTPRE, RHOBTB1) [51,52], chondrogenesis (SCFD) [53,54], lipid and carbohydrate metabolism (PPARD, GCG, TCF7L2, GALNT13) [55–58], exercise stress-induced response (CD69, EIF4G3) [59,60], exercise coordination (GRM1) [61,62], and height (VGLL4) [30]. These genes of positive selection were presented simultaneously in Abaga horse, which may be a reason that it runs faster than Wushen horse.
4 Discussion
Many genes of the positively selected 479 and 943 genes were enriched on chromosome 4, and the enrichment quantity of the positively selected genes was secondary by the chromosome enrichment analysis both in Abaga horse and Wushen horse. In the statement of Schröder et al. [29], athletic performance-related genes were significantly enriched on chromosomes 4 and 12 of horses, which coincided with the different traits of running speed in our exploring direction. Possibly, we will take equine chromosome 4 as the exercise-related emphasis of scientific research.
The athletic ability of the horse may be influenced not only by physiology but also by thought and motive. According to the previous studies, equine exercise-related genes included DRD1-5, SLC6A4, and BDNF, the three gene functions were related to many neurological processes, involving motivation, pleasure, cognition, memory, learning, fine motor control, modulation of neuroendocrine signaling, the adaptive ability to control emotions, supporting the survival of existing neurons, encouraging the growth, and differentiation of new neurons and synapses [64–67]. The GO analysis results of the Abaga horse were also preferentially enriched in neuronal composition, neurotransmission, and brain cell migration. These genes may allow the Abaga horse to quickly observe and distinguish the surrounding during moving at high speed, and timely rectify the status to respond to various circumstances.
In this research, 13 positively selected genes were enriched in the PI3K-Akt signaling pathway. As intracellular basal signaling pathways, the PI3K-Akt signaling pathway involves lots of vital movement, such as exercise-induced physiologic hypertrophy [21,23,24,26] and protecting mitochondria of skeletal muscle by aerobic endurance training [27], further explaining the excellent athletic performance of Abaga horse. Besides the PI3K-Akt signaling pathway, we also found many exercise-related pathways that were metabolic pathways, arachidonic acid metabolism, regulation of actin cytoskeleton, fatty acid metabolism, Ras signaling pathway, MAPK signaling pathway, Hippo signaling pathway, valine, leucine, and isoleucine degradation, cardiac muscle contraction, NF-kappa B signaling pathway, and insulin signaling pathway [20,22,25,28–32] (Table 3). But, in our study, the enriched genes of positive selection were different from the previously studied genes in the above exercise-related pathways (Table 3), which indicated species-specific genes of positive selection in Abaga horse compared with other species (human, rat, mouse, leopard, Thoroughbred horse, etc.).
Comparison of enriched genes in candidate pathways between our data and previous studies of Abaga horse
KEGG pathway | ID | Selected genes in Abaga horse | Selected genes or proteins in previous studies |
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Metabolic pathways | ecb01100 | LTA4H AGK PNPLA3 ITPK1 NDUFB7 RIMKLA PCCB ACAD8 ACMSD BST1 CPOX | CYP51A1 |
Ras signaling pathway | ecb04014 | SHC4 GNG11 GNGT1 KSR2 TBK1 ABL2 | APOA1 IGF-1 HRAS |
PI3K-Akt signaling pathway | ecb04151 | LAMC2 GNG11 GNGT1 MYB | PGC-1a IGF-1 IGF-1R ErbB2 ErbB4 |
MAPK signaling pathway | ecb04010 | CACNA1I CACNA2D3 CACNB4 MAP3K4 | ERK AP-1 |
Hippo signaling pathway | ecb04390 | MPP5 TCF7L2 | WWTR1 LATS2 TEAD YAP1 VGLL2 VGLL3 VGLL4 |
Cardiac muscle contraction | ecb04260 | CACNA2D3 CACNB4 | CK-M |
NF-kappa B signaling pathway | ecb04064 | CARD10 TRAF1 | MnSOD iNOS |
Arachidonic acid metabolism | ecb00590 | LTA4H | PTGS1 |
Regulation of actin cytoskeleton | ecb04810 | ENAH | GSN BDKRB2 CHRM MYLK ACTN3 |
Insulin signaling pathway | ecb04910 | SHC4 | GYS1 PPARGC1A |
Fatty acid metabolism | ecb01212 | ELOVL5 | ADHFE1 SREBP2 |
Counting on exercise-related genes of previous studies, the equine athletic performance is related to glucose metabolism, stress immune response, angiogenesis and muscle supply, insulin signal transduction, fat substrate application, muscle strength, and the formation of bones and cartilage with growth [2–4,20,68]. We picked up exercise-related genes as candidate genes in positively selected genes, and further, presented enriched KEGG pathways and functions with the selected exercise-related genes (Figure 6). HTR2B (encoding 5-hydroxytryptamine receptor 2B) has been identified in the genome of Quarter horses of the racing line [6] and is associated with impulsive behavior [35] and vasoconstriction [34]. A recent research shows that HTR2B are specific markers in age-related osteoarthritis and involved in apoptosis and inflammation of osteoarthritis synovial cells [69]. In zebrafish, vascular endothelial cadherin (encoded by CDH5) can promote elongation of the endothelial cell interface during angiogenesis [36]. KCNQ1 (encoding KvLQT1, a potassium channel protein) is related to exercise, and mutation of KCNQ1 and KCNE1 can cause susceptibility of sudden cardiac death for a horse [37–39]. Mena (encoded by ENAH) which is located in the Z line that the borders of the sarcomere, VASP, and αII-Spectrin assemble cardiac multi-protein complexes to regulate cytoplasmic actin networks [40,41]. PIH1D1 (encoding the components of the apoptotic regulatory complex R2TP) is relevant to muscle mass [42,43]. Because E3 ubiquitin-protein ligase SMURF1 (encoded by SMURF1) functions as negative regulator of myostatin pathway activity and myostatin is a negative regulator of skeletal muscle mass, up-regulated expression of SMURF1 may link to skeletal muscle growth following prolonged training [44]. UNC13C is connected with the differentiation of myoblast while integral myotubes originate in myoblast differentiation and raise the distinct muscle fiber types to build the complex skeletal muscle architecture for body movement, postural behavior, and breathing [45,46]. ATP1A3 encodes subunit alpha-3 of sodium/potassium-transporting ATPase, which increased the expression and may be conducive to decreasing fatigue after training [47,48]. ATP1A3 gene mutations can result in the rapid-onset dystonia-parkinsonism [70]. PPARD (encoding peroxisome proliferator-activated receptor delta) participates in regulation of energy metabolism, cell proliferation, and differentiation, protection in stress conditions such as oxidative stress and inflammation, and other important life activities [57]. The antecedent studies have shown that the Arabian horse will change the expression of PPARD and other genes of PPAR signaling pathway genes in skeletal muscle during exercise, and improve the coefficient of utilization of fatty acids by energy conversion [58]. The up-regulated PPARD is also found after exercise in the Thoroughbred horse [3]. So, we speculated that positively selected PPARD improved athletic ability by a similar mechanism in Abaga horse. Besides the counter-regulatory hormone of insulin, GCG (encoding glucagon) is deemed to be involved in adipose metabolism and energy balance [35]. Transcription factor 7-like 2 (encoded by TCF7L2) not only affects the metabolism of adipocytes by DNA methylation but also activates the corresponding target genes through the Wnt signaling pathway to specifically inhibit glucagon synthesis in enteroendocrine cells [55]. GALNT13 may be involved in metabolic and energy pathways [56].
Exercise has a great influence on the composition of developing horse joints, the thickness of the hyaline cartilage of the adult horse, the calcified cartilage, and the subchondral bone [71,72]. We found several genes associated with skeleton and cartilage development among candidate genes of the Abaga horse. PPP2R5B and PPP6R3 are closely related to femur strength in rats and bone mineral density in humans, respectively [49,50]. PTPRE encodes receptor-type tyrosine-protein phosphatase epsilon which is a positive regulator of osteoclast function [51]. RHOBTB1 is involved in osteoclast-mediated bone absorption activity [52]. REA (LRRFIP1, RCAN1, and RHOBTB1) and IF (TRIP12, HSPE1, and MAP2K6) have an important role to play in muscle cell degradation, development, and motility from Nelore cattle [73]. Chondrogenesis demands transformation of chondrocytes from a simple mesenchymal condensation to cells with a highly enriched extracellular matrix (ECM) in the developing skeleton in which SCFD1 plays an important role in the secretion of ECM protein during chondrogenesis [53,54]. So far there are no studies on the association between these genes and the motor function of horses, but these skeleton- and cartilage-related genes provide new inspiration for the correlational research between ossature and exercise.
After exercise, the equine stress reaction will involve inflammation, cell signaling, and immune interactions [4]. Cell activation is the first step in the proliferation of immune cells, and CD69 is first detected in cell surface glycoproteins after activation [74]. The low- to moderate-intensity aerobic trekking induces activation of CD69 T cells and promotes anti-stress effects on the oxidative balance and the high-altitude-induced injury of the immune responses among women [60]. EIF4G3 encodes eukaryotic translation initiation factor 4 gamma 3 which is indispensable for triggering protein synthesis and is thought to be involved in exercise stress-induced response in horses [59,75]. We hypothesized that these genes may be involved in the ability of Abaga horses to enhance certain disease resistance through exercise, but more data and experiments are needed to verify.
GRM1 encodes metabotropic glutamate receptor 1, whose deficiency can lead to serious deficits in motor coordination and spatial learning in mice [61,62]. The effectors of the Hippo signal pathway regulate several motor-related genes and adaptations while VGLL4 is Hippo-signal-related to body height [30]. These exercise-related genes were positively selected in the Abaga horse, indicating that the Abaga horse has exercise-related genetic potential compared with the Wushen horse.
5 Conclusion
We generated and analyzed the genomic data of the Abaga horse and Wushen horse by sequencing. We uncovered that chromosome 4 may be associated with the evolution of athletic performance in the Mongolian horse. The positively selected genes of the Abaga horse were enriched in exercise-related pathways, which suggest that the Abaga horse may have an exclusively physiological mechanism for the motorial process. Moreover, 21 exercise-related genes were detected. These findings provided a molecular genetic basis for exercise-directed breeding of Mongolian horses.
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Funding information: Authors state no funding involved.
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Author contributions: H.M.Z. conceived the study and designed the experiments. J.P. and Y.B.L. participated in sampling and performed the experiments. H.W.Z., Z.P.Z., and F.W. conducted a bioinformatics analysis of the data. J.P. analyzed the biological function of the data and wrote the manuscript. H.M.Z., C.P., NASHUNWENDOULE, and G.C.Q. provided valuable insights in the discussion and revision of the manuscript. All authors read and approved the final manuscript.
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Conflict of interest: Authors state no conflict of interest.
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Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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- Functional constituents of plant-based foods boost immunity against acute and chronic disorders
- Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
- Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
- Ecology and Environmental Sciences
- Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
- Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
- Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
- Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
- Plant volatile organic compounds attractive to Lygus pratensis
- Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
- Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
- Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
- Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
- Bioengineering and Biotechnology
- Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
- Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
- Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
- Agriculture
- Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
- Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
- Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
- Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
- Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
- Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
- Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
- Animal Sciences
- Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
- Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
- SI: A Scientific Memoir
- Suggestions on leading an academic research laboratory group
- My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
- Erratum
- Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
- Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
- Retraction
- Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
Articles in the same Issue
- Biomedical Sciences
- Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
- The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
- Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
- LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
- Association study of CLDN14 variations in patients with kidney stones
- Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
- Regulation of miR-30b in cancer development, apoptosis, and drug resistance
- Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
- Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
- Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
- Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
- Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
- Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
- Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
- Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
- Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
- Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
- Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
- Nutrition intervention in the management of novel coronavirus pneumonia patients
- circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
- Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
- Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
- Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
- Comparison of axon extension: PTFE versus PLA formed by a 3D printer
- Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
- A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
- Study on the mechanism of inhibiting patulin production by fengycin
- SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
- Relationship between blood clots and COVID-19 vaccines: A literature review
- Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
- Bioinformatics network analyses of growth differentiation factor 11
- NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
- Expression of Zeb1 in the differentiation of mouse embryonic stem cell
- Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
- Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
- Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
- Genetic susceptibility to high myopia in Han Chinese population
- Potential biomarkers and molecular mechanisms in preeclampsia progression
- Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
- Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
- The significance of PAK4 in signaling and clinicopathology: A review
- Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
- Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
- Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
- Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
- MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
- Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
- BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
- Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
- Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
- A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
- Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
- Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
- Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
- A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
- β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
- Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
- BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
- Mucormycosis co-infection in COVID-19 patients: An update
- Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
- Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
- Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
- Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
- Nasopharyngeal tuberculosis: A case report
- Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
- Aberrant pulmonary immune response of obese mice to periodontal infection
- Bacteriospermia – A formidable player in male subfertility
- In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
- Effects of KCa channels on biological behavior of trophoblasts
- Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
- Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
- Prognostic signature related to the immune environment of oral squamous cell carcinoma
- Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
- Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
- Role of MMP-2 and CD147 in kidney fibrosis
- Geometric basis of action potential of skeletal muscle cells and neurons
- Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
- Role of cerebellar cortex in associative learning and memory in guinea pigs
- Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
- Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
- Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
- Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
- Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
- Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
- Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
- Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
- One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
- S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
- Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
- Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
- Evaluation of prognostic markers in patients infected with SARS-CoV-2
- N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
- Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
- Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
- Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
- Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
- Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
- Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
- SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
- Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
- Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
- Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
- Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
- Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
- PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
- A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
- Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
- A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
- The role of erythrocytes and erythroid progenitor cells in tumors
- Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
- Abnormal methylation caused by folic acid deficiency in neural tube defects
- Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
- Plant Sciences
- Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
- Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
- Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
- Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
- Phytoremediation of pollutants from wastewater: A concise review
- Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
- Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
- Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
- Study on pecan seed germination influenced by seed endocarp
- Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
- The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
- Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
- Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
- Cloning and expression analysis of SERK1 gene in Diospyros lotus
- Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
- A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
- Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
- The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
- Food Science
- Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
- Binge eating disorder during COVID-19
- Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
- FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
- Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
- Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
- Functional constituents of plant-based foods boost immunity against acute and chronic disorders
- Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
- Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
- Ecology and Environmental Sciences
- Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
- Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
- Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
- Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
- Plant volatile organic compounds attractive to Lygus pratensis
- Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
- Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
- Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
- Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
- Bioengineering and Biotechnology
- Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
- Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
- Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
- Agriculture
- Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
- Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
- Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
- Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
- Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
- Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
- Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
- Animal Sciences
- Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
- Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
- SI: A Scientific Memoir
- Suggestions on leading an academic research laboratory group
- My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
- Erratum
- Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
- Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
- Retraction
- Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”