Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak.

Protein lysine lactylation, a recently discovered post-translational modification (PTM), is prevalent across tissues and cells of diverse species, serving as a regulator of glycolytic flux and biological metabolism. The yak (Bos grunniens), a species that has inhabited the Qinghai-Tibetan Plateau for millennia, has evolved intricate adaptive mechanisms to cope with the region's unique geographical and climatic conditions, exhibiting remarkable energy utilization and metabolic efficiency. Nonetheless, the specific landscape of lysine lactylation in yaks remains poorly understood. Herein, we present the first comprehensive lactylome profile of the yak, effectively identifying 421, 308, and 650 lactylated proteins in the heart, muscles, and liver, respectively. These lactylated proteins are involved in glycolysis/gluconeogenesis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolic process encompassing carbohydrates, lipids, and proteins during both anaerobic and aerobic glucose bio-oxidation, implying their crucial role in material and energy metabolism, as well as in maintaining homeostasis in yaks.

Yak genome database: a multi-omics analysis platform.

BACKGROUND: The yak (Bos grunniens) is a large ruminant species that lives in high-altitude regions and exhibits excellent adaptation to the plateau environments. To further understand the genetic characteristics and adaptive mechanisms of yak, we have developed a multi-omics database of yak including genome, transcriptome, proteome, and DNA methylation data. DESCRIPTION: The Yak Genome Database ( http://yakgenomics.com/ ) integrates the research results of genome, transcriptome, proteome, and DNA methylation, and provides an integrated platform for researchers to share and exchange omics data. The database contains 26,518 genes, 62 transcriptomes, 144,309 proteome spectra, and 22,478 methylation sites of yak. The genome module provides access to yak genome sequences, gene annotations and variant information. The transcriptome module offers transcriptome data from various tissues of yak and cattle strains at different developmental stages. The proteome module presents protein profiles from diverse yak organs. Additionally, the DNA methylation module shows the DNA methylation information at each base of the whole genome. Functions of data downloading and browsing, functional gene exploration, and experimental practice were available for the database. CONCLUSION: This comprehensive database provides a valuable resource for further investigations on development, molecular mechanisms underlying high-altitude adaptation, and molecular breeding of yak.

Genome-wide comparison of DNA methylation patterns between yak and three cattle strains and their potential association with mRNA transcription.

Yak has evolved specific adaptative mechanisms to high-altitude environment. Up to date, only a few studies reported the DNA methylation in yak. In the present study, genome-wide DNA methylome and transcriptome profiles in lung, mammary, and biceps brachii muscle tissues were compared between yak and three cattle breeds (Tibetan cattle, Sanjiang cattle, and Holstein cattle). The association between differentially expressed genes (DEGs) and differentially methylated regions (DMRs) was analyzed, and the biological functions of DEGs potentially driven by DMRs were explored by KEGG enrichment analysis. Finally, we found that yak-specific DMRs-driven DEGs were mainly involved in neuromodulation, respiration, lung development, blood pressure regulation, cardiovascular protection, energy metabolism, DNA repair, and immune functions. The higher levels of the key genes associated with these functions were observed in yak than in cattle, suggesting that DNA methylation might regulate these genes. Overall, the present study contributes basic data at the DNA methylation level to further understand the physiological metabolism in yak.

Genome-wide identification of SNPs associated with body weight in yak.

BACKGROUND: The yak is the most important livestock in the Qinghai-Tibet Plateau, and body weight directly affects the economic values of yak. Up to date, the genome-wide profiling of single-nucleotide polymorphisms (SNPs) associating with body weight has not been reported in yak. In the present study, the SNPs in 480 yaks from three breeds were analyzed using the commercial high-density (600 K) yak SNP chips. RESULTS: The results identified 12 and 4 SNPs potentially associated with body weight in male and female yaks, respectively. Among them, 9 and 2 SNPs showed significant difference in yak body weight between different genotypes at each locus in male and female yaks, respectively. Further exploration found 33 coding genes within the 100 kbp upstream or downstream to the SNP loci, which might be potentially affected by the variation of SNPs. Among them, G protein-coupled receptor kinase 4 (GRK4) might be potentially affected by the SNP AX-174555047, which has been reported to affect the functioning of two body-weight associated hormones (parathyroid hormone, PTH, and adrenomedullin, ADM). Determination of PTH and ADM levels in yak revealed positive relationship between PTH level and body weight, negative relationship between ADM level and body weight along with the variation of AX-174555047 mutation. CONCLUSIONS: These results suggested that the SNP AX-174555047 might potentially affect body weight through mediating GRK4 expression and then PTH and ADM functioning. Thus, the SNP AX-174555047 might be used as a biomarker for molecular breeding of yak. More investigations are required to validate this point.

Dynamic alterations in yak (Bos grunniens) rumen microbiome in response to seasonal variations in diet.

Rumen microorganisms play important roles in the healthy growth of yaks. This study investigated changes in yak rumen microbiome during natural grazing at the warm seasons and supplementary feeding at cold seasons. High-throughput sequencing of 16S rRNA and metagenome analysis were conducted to investigate the structures and functions of yak rumen microbial communities. The results indicated that Bacteroidetes and Firmicutes were the most abundant phyla. In addition, Bacteroidetes might play a more important role than Firmicutes during the supplementary feeding stage (spring and winter), but less during natural grazing stage (summer and autumn). KEGG analysis showed that the amino sugar and nucleotide sugar metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, starch and sucrose metabolism, and fructose and mannose metabolism were the main pathways in the microbial community, which were significantly different between seasons. The carbohydrate-active enzymes (CAZyme) annotation revealed that cellulose was an important carbon source for microorganisms in yak rumen. Glycoside hydrolases (GHs) were the most abundant class of CAZymes, followed by glycosyl transferases (GTs), which were important to digestion of oil, cellulose, and hemicellulose in food. These results contribute to the understanding of microbial components and functions in yak rumen.

Codon Usage Bias and Cluster Analysis of the MMP-2 and MMP-9 Genes in Seven Mammals.

Matrix metalloproteinase (MMP)-2 and MMP-9 are a family of Zn2+ and Ca2+-dependent gelatinase MMPs that regulate muscle development and disease treatment, and they are highly conservative during biological evolution. Despite increasing knowledge of MMP genes, their evolutionary mechanism for functional adaption remains unclear. Moreover, analysis of codon usage bias (CUB) is reliable to understand evolutionary associations. However, the distribution of CUB of MMP-2 and MMP-9 genes in mammals has not been revealed clearly. Multiple analytical software was used to study the genetic evolution, phylogeny, and codon usage pattern of these two genes in seven species of mammals. Results showed that the MMP-2 and MMP-9 genes have CUB. By comparing the content of synonymous codon bases amongst seven mammals, we found that MMP-2 and MMP-9 were low-expression genes in mammals with high codon conservation, and their third codon preferred the G/C base. RSCU analysis revealed that these two genes preferred codons encoding delicious amino acids. Analysing what factors influence CUB showed that the third base distributors of these two genes were C/A and C/T, and GC3S had a wide distribution range on the ENC plot reference curve under no selection or mutational pressure. Thus, mutational pressure is an important factor in CUB. This study revealed the usage characteristics of the MMP-2 and MMP-9 gene codons in different mammals and provided basic data for further study towards enhancing meat flavour, treating muscle disease, and optimizing codons.

Differences in proteomic profiles between yak and three cattle strains provide insights into molecular mechanisms underlying high-altitude adaptation.

Yaks display unique properties of the lung and heart, enabling their adaptation to high-altitude environments, but the underlying molecular mechanisms are still largely unknown. In the present study, the proteome differences in lung and heart tissues were compared between yak (Bos grunniens) and three cattle strains (Bos taurus, Holstein, Sanjiang and Tibetan cattle) using the sequential window acquisition of all theoretical mass spectra/data-independent acquisition (SWATH/DIA) proteomic method. In total, 51,755 peptides and 7215 proteins were identified. In the lung tissue, there were 162, 310 and 118 differential abundance proteins (DAPs) in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. In the heart tissue, there were 71, 57 and 78 DAPs in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DAPs were enriched for the retinol metabolism and toll-like receptor categories in lung tissue. The changes in these two pathways may regulate hypoxia-induced factor and immune function in yaks. Moreover, DAPs in heart tissues were enriched for cardiac muscle contraction, Huntington's disease, chemical carcinogenesis and drug metabolism-cytochrome P450. Further exploration indicated that yaks may alter cardiac function through regulation of type 2 ryanodine receptor (RyR2) and Ca2+ -release channels. The present results are useful to further develop an understanding of the mechanisms underlying adaptation of animals to high-altitude conditions.

Genome-Wide DNA Methylation and Hydroxymethylation Changes Revealed Epigenetic Regulation of Neuromodulation and Myelination in Yak Hypothalamus.

Both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are important epigenetic modifications in neurodevelopment. However, there is little research examining the genome-wide patterns of 5mC and 5hmC in brain regions of animals under natural high-altitude conditions. We used oxidative reduced representation bisulfite sequencing (oxRRBS) to determine the 5mC and 5hmC sites in the brain, brainstem, cerebellum, and hypothalamus of yak and cattle. We reported the first map of genome-wide DNA methylation and hydroxymethylation in the brain, brainstem, cerebellum, and hypothalamus of yak (living at high altitudes) and cattle. Overall, we found striking differences in 5mC and 5hmC between the hypothalamus and other brain regions in both yak and cattle. Genome-wide profiling revealed that 5mC level decreased and 5hmC level increased in the hypothalamus than in other regions. Furthermore, we identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DhMRs), most of which overlapped with each other. Interestingly, transcriptome results for these brain regions also showed distinctive gene levels in the hypothalamus. Finally, differentially expressed genes (DEGs) regulated by DMRs and DhMRs may play important roles in neuromodulation and myelination. Overall, our results suggested that mediation of 5mC and 5hmC on epigenetic regulation may broadly impact the development of hypothalamus and its biological functions.

Comparison of Gut Microbiota of Yaks From Different Geographical Regions.

Gut microbiota are closely linked to host health and adaptability to different geographical environments. However, information on the influence of different geographical conditions on the intestinal microbiota of yaks is limited. In this study, 18 yak fecal samples were collected from three regions of China, namely Shangri-la, Lhasa, and Yushu, and were analyzed via high-throughput sequencing. The alpha diversity, as measured by the Shannon, ACE, and Chao indices, was the highest in the Shangri-la samples. Principal coordinate analysis detected significant differences in the composition of the intestinal microbiota of yaks from different regions. A total of six phyla, 21 families, and 29 genera were identified in the fecal samples. The dominant phyla in the samples were Firmicutes and Bacteroidetes, and the most abundant family was Ruminococcaceae. In addition, Ruminococcaceae_UCG-005 was the predominant genus and was more abundant in Yushu samples than in other samples. However, the predicted functional gene composition of the gut microbiota of yaks from different regions was similar. Our results revealed that geographical conditions influence the diversity and composition of the intestinal microbiota of yaks.

Whole-Transcriptome Analysis of Yak and Cattle Heart Tissues Reveals Regulatory Pathways Associated With High-Altitude Adaptation.

BACKGROUND: The yak (Bos grunniens) is an important livestock species that can survive the extremely cold, harsh, and oxygen-poor conditions of the Qinghai-Tibetan Plateau and provide meat, milk, and transportation for the Tibetans living there. However, the regulatory network that drive this hypoxic adaptation remain elusive. RESULTS: The heart tissues from LeiRoqi (LWQY) yak and their related cattle (Bos Taurus) breeds, which are two native cattle breeds located in high altitude (HAC) and low altitude (LAC) regions, respectively, were collected for RNA sequencing. A total of 178 co-differentially expressed protein-coding transcripts (co-DETs) were discovered in each of the LAC-vs-LWQY and LAC-vs-HAC comparison groups, including NFATC2, NFATC1, ENPP2, ACSL4, BAD, and many other genes whose functions were reported to be associated with the immune-system, endocrine-system, and lipid metabolism. Two and 230 lncRNA transcripts were differentially expressed in the LAC-vs-LWQY and LAC-vs-HAC comparisons' respectively, but no lncRNA transcripts that were co-differentially expressed. Among the 58 miRNAs that were co-differentially expressed, 18 were up-regulated and 40 were down-regulated. In addition, 640 (501 up-regulated and 139 down-regulated) and 152 (152 up-regulated and one down-regulated) circRNAs showed differential expression in LAC-vs-LWQY and LAC-vs-HAC comparison groups, respectively, and 53 up-regulated co-differentially expressed circRNAs were shared. Multiple co-DETs, which are the targets of miRNAs/lncRNAs, are significantly enriched in high-altitude adaptation related processes, such as, T cell receptor signaling, VEGF signaling, and cAMP signaling. A competing endogenous RNA (ceRNA) network was constructed by integrating the competing relationships among co-differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs. Furthermore, the hypoxic adaptation related ceRNA network was constructed, and the six mRNAs (MAPKAPK3, PXN, NFATC2, ATP7A, DIAPH1, and F2R), the eight miRNAs (including miR-195), and 15 circRNAs (including novel-circ-017096 and novel-circ-018073) are proposed as novel and promising candidates for regulation of hypoxic adaptation in the heart. CONCLUSION: In conclusion, the data recorded in the present study provides new insights into the molecular network of high-altitude adaptation along with more detailed information of protein-coding transcripts and non-coding transcripts involved in this physiological process, the detailed mechanisms behind how these transcripts "crosstalk" with each other during the plateau adaptation are worthy of future research efforts.

Qingke ß-glucan synergizes with a ß-glucan-utilizing Lactobacillus strain to relieve capsaicin-induced gastrointestinal injury in mice.

Capsaicin (CAP) is the main pungent component in capsicum fruits. Eating too much CAP leads to gastrointestinal injury. Previously, Qingke ß-glucan combined with ß-glucan-utilizing Lactobacillus plantarum S58 (LP.S58) ameliorated high fat-diet-induced obesity, but their effects on CAP-induced gastrointestinal injury have not been investigated. Our results showed that Qingke ß-glucan reduced the CAP-induced gastrointestinal injury in Kunming mice. The serum levels of inflammatory cytokines and gastrointestinal hormones, and the localized inflammation and the expression of EGF, EGFR, VEGF, and ZO-1 in the gastrointestinal tissues in CAP-treated mice were partly restored by Qingke ß-glucan. The CAP-induced increase in the abundances of proinflammatory intestinal bacteria was also reduced by Qingke ß-glucan. More importantly, we found that these beneficial effects of Qingke ß-glucan were markedly enhanced by ß-glucan-utilizing LP.S58 supplementation. Our study indicated that Qingke ß-glucan coupled with ß-glucan-utilizing LP.S58 relieved CAP-induced gastrointestinal injury.

A chromosome-scale reference genome and genome-wide genetic variations elucidate adaptation in yak.

Yak is an important livestock animal for the people indigenous to the harsh, oxygen-limited Qinghai-Tibetan Plateau and Hindu Kush ranges of the Himalayas. The yak genome was sequenced in 2012, but its assembly was fragmented because of the inherent limitations of the Illumina sequencing technology used to analyse it. An accurate and complete reference genome is essential for the study of genetic variations in this species. Long-read sequences are more complete than their short-read counterparts and have been successfully applied towards high-quality genome assembly for various species. In this study, we present a high-quality chromosome-scale yak genome assembly (BosGru_PB_v1.0) constructed with long-read sequencing and chromatin interaction technologies. Compared to an existing yak genome assembly (BosGru_v2.0), BosGru_PB_v1.0 shows substantially improved chromosome sequence continuity, reduced repetitive structure ambiguity, and gene model completeness. To characterize genetic variation in yak, we generated de novo genome assemblies based on Illumina short reads for seven recognized domestic yak breeds in Tibet and Sichuan and one wild yak from Hoh Xil. We compared these eight assemblies to the BosGru_PB_v1.0 genome, obtained a comprehensive map of yak genetic diversity at the whole-genome level, and identified several protein-coding genes absent from the BosGru_PB_v1.0 assembly. Despite the genetic bottleneck experienced by wild yak, their diversity was nonetheless higher than that of domestic yak. Here, we identified breed-specific sequences and genes by whole-genome alignment, which may facilitate yak breed identification.

Methylome and transcriptome profiles in three yak tissues revealed that DNA methylation and the transcription factor ZGPAT co-regulate milk production.

BACKGROUND: Domestic yaks play an indispensable role in sustaining the livelihood of Tibetans and other ethnic groups on the Qinghai-Tibetan Plateau (QTP), by providing milk and meat. They have evolved numerous physiological adaptations to high-altitude environment, including strong blood oxygen transportation capabilities and high metabolism. The roles of DNA methylation and gene expression in milk production and high-altitudes adaptation need further exploration. RESULTS: We performed genome-wide DNA methylome and transcriptome analyses of breast, lung, and biceps brachii muscle tissues from yaks of different ages. We identified 432,350 differentially methylated regions (DMRs) across the age groups within each tissue. The post-mature breast tissue had considerably more differentially methylated regions (155,957) than that from the three younger age groups. Hypomethylated genes with high expression levels might regulate milk production by influencing protein processing in the endoplasmic reticulum. According to weighted gene correlation network analysis, the "hub" gene ZGPAT was highly expressed in the post-mature breast tissue, indicating that it potentially regulates the transcription of 280 genes that influence protein synthesis, processing, and secretion. The tissue network analysis indicated that high expression of HIF1A regulates energy metabolism in the lung. CONCLUSIONS: This study provides a basis for understanding the epigenetic mechanisms underlying milk production in yaks, and the results offer insight to breeding programs aimed at improving milk production.

Transcriptome analysis identified long non-coding RNAs involved in the adaption of yak to high-altitude environments.

The mechanisms underlying yak adaptation to high-altitude environments have been investigated using various methods, but no report has focused on long non-coding RNA (lncRNA). In the present study, lncRNAs were screened from the gluteus transcriptomes of yak and their transcriptional levels were compared with those in Sanjiang cattle, Holstein cattle and Tibetan cattle. The potential target genes of the differentially expressed lncRNAs between species/strains were predicted using cis and trans models. Based on cis-regulated target genes, no KEGG pathway was significantly enriched. Based on trans-regulated target genes, 11 KEGG pathways in relation to energy metabolism and three KEGG pathways associated with muscle contraction were significantly enriched. Compared with cattle strains, transcriptional levels of acyl-CoA dehydrogenase, acyl-CoA-binding protein, 3-hydroxyacyl-CoA dehydrogenase were relatively higher and those of glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate mutase 1, pyruvate kinase and lactate/malate dehydrogenase were relatively lower in yak, suggesting that yaks activated fatty acid oxidation but inhibited glucose oxidation and glycolysis. Besides, NADH dehydrogenase and ATP synthase showed lower transcriptional levels in yak than in cattle, which might protect muscle tissues from deterioration caused by reactive oxygen species (ROS). Compared with cattle strains, the higher transcriptional level of glyoxalase in yak might contribute to dicarbonyl stress resistance. Voltage-dependent calcium channel/calcium release channel showed a lower level in yak than in cattle strains, which could reduce the Ca2+ influx and subsequently decrease the risk of hypertension. However, levels of EF-hand and myosin were higher in yak than in cattle strains, which might enhance the negative effects of reduced Ca2+ on muscle contraction. Overall, the present study identified lncRNAs and proposed their potential regulatory functions in yak.

Whole-genome resequencing provides insights into the evolution and divergence of the native domestic yaks of the Qinghai-Tibet Plateau.

BACKGROUND: On the Qinghai-Tibet Plateau, known as the roof ridge of the world, the yak is a precious cattle species that has been indispensable to the human beings living in this high-altitude area. However, the origin of domestication, dispersal route, and the divergence of domestic yaks from different areas are poorly understood. RESULTS: Here, we resequenced the genome of 91 domestic yak individuals from 31 populations and 1 wild yaks throughout China. Using a population genomics approach, we observed considerable genetic variation. Phylogenetic analysis suggested that the earliest domestications of yak occurred in the south-eastern QTP, followed by dispersal to the west QTP and northeast to SiChuang, Gansu, and Qinghai by two routes. Interestingly, we also found potential associations between the distribution of some breeds and historical trade routes such as the Silk Road and Tang-Tibet Ancient Road. Selective analysis identified 11 genes showing differentiation between domesticated and wild yaks and the potentially positively selected genes in each group were identified and compared among domesticated groups. We also detected an unbalanced pattern of introgression among domestic yak, wild yak, and Tibetan cattle. CONCLUSIONS: Our research revealed population genetic evidence for three groups of domestic yaks. In addition to providing genomic evidence for the domestication history of yaks, we identified potential selected genes and introgression, which provide a theoretical basis and resources for the selective breeding of superior characters and high-quality yak.

Differential expression profile of microRNA in yak skeletal muscle and adipose tissue during development.

BACKGROUND: miRNAs play an important role in regulating normal animal development. Muscle tissue and fat metabolism are important for maintaining energy balance in animals. Yak has important agricultural and economic importance as it provides milk, meat, and hair. It is used for transportation as well. However, the miRNA expression profiles of their muscle and adipose tissue are currently unknown. OBJECTIVE: To explore the regulatory roles of miRNAs in the skeletal muscle and adipose tissues of yak. METHODS: A total of 12 small RNA libraries were constructed from the skeletal muscle and adipose samples from yak aged 0.5, 2.5, 4.5, and 7.5 years. High-throughput sequencing and bioinformatics analysis were used to determine the dynamic expression profile of miRNA, and a miRNA regulatory network related to muscle and adipose tissue development was established. RESULTS: miR-1-3p and miR-143-3p showed the highest expression during yak skeletal muscle and fat development, respectively. The MAPK and Ras signaling pathways were the pivotal pathways. miR-181-5p, miR-542-3p, and miR-424-5p may have key roles in skeletal muscle development, and CREBRF, GRB10, CDK1, RFX3, and EPC2 were the core target genes. While miR-127-5p, miR-379-3p, and miR-494-3p may play important regulatory roles in adipose deposition, and ETV1, XPO7, and C5AR2 were the core target genes. CONCLUSION: This study provides valuable resources for further study of the molecular mechanisms underlying yak skeletal muscle and adipose tissue development, and also a basis for studying the interactions between genes and miRNAs.

Signature of high altitude adaptation in the gluteus proteome of the yak.

Yak is the unique Bovidae species in the Qinghai-Tibetan Plateau. A previous proteomic study has compared the yak muscle tissue to one cattle strain using the isobaric tags for relative and absolute quantification approach. In this study, to further investigate the molecular mechanisms underlying yak adaptation, the proteomic profiles of gluteus were compared between yak and one moderate-altitude cattle strain (Tibetan cattle) and two low-altitude cattle strains (Holstein and Sanjiang cattle) using a label-free quantitative method. The comparisons identified 20, 364, 143 upregulated proteins and 4, 6, 37 downregulated proteins in yak, compared with Tibetan, Holstein, and Sanjiang cattle, respectively. Protein-protein interaction analysis indicated that these differentially expressed proteins were mainly related to "oxidative phosphorylation" and "electron transport chain." Further analysis revealed that NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4, cytochrome C oxidase subunit 6A2, mitochondrial and cytochrome c oxidase subunit NDUFA4 were all increased in the yak, suggesting that yak might increase mitochondrial capacity to sustain metabolic rates under high altitude conditions, which might be a long-term adaptive mechanism underlying adaptation to high altitude environments. Yak increased the level of thioredoxin reductase 2 to protect themselves from oxidative damages. Moreover, the increased expression levels of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform and caveolin-1 in yak suggested that yaks promoted glucose uptake for adaptation to high altitude. These results provided more information to better understand the molecular mechanisms underlying yak adaption.

Comparisons of lung and gluteus transcriptome profiles between yaks at different ages.

The yak, Bos grunniens, is the only large mammal in the Qinghai-Tibet Plateau and has been bred to provide meat, milk, and transportation. Previous studies indicate that the immune system contributes to the yak's adaptation to high-altitude environments. In order to further investigate changes in immune function during yak development, we compared the transcriptome profiles of gluteus and lung tissues among yaks at 6, 30, 60, and 90 months of age. Analyses of significantly differentially expressed genes (DEGs) in lung tissues revealed that immune function was more activated at 6-months and less activated at 90-months than in the 30 and 60-month-old animals. DEG exploration in gluteal tissues revealed that immune functions were more highly activated at both 6 and 90-months, compared with 30 and 60-months. Immune system activation in the muscle and lung tissues of 30-month-old yaks may increase their resistance to infections, while decreased may be due to aging. Furthermore, the higher immune activation status in the gluteal tissues in 90-month-old yaks could be due to muscle injury and subsequent regeneration, which is supported by the fact that 5 unigenes related with muscle injury and 3 related to muscle regeneration displayed greater expression levels at 90-months than at 30 and 60-months. Overall, the present study highlights the important role of the immune system in yak development, which will facilitate future investigations.

Comparing the Microbial Community in Four Stomach of Dairy Cattle, Yellow Cattle and Three Yak Herds in Qinghai-Tibetan Plateau.

Yak (Bos grunniens) is an unique ruminant species in the Qinghai-Tibetan Plateau (QTP). The ruminant gastrointestinal tract (GIT) microbiota is not only associated with the nutrients metabolism, but also contributes to the host's local adaptation. Examining the microbiota between cattle and yak in different geography could improve our understanding about the role of microbiota in metabolism and adaptation. To this end, we compared the microbiota in rumen, reticulum, omasum, and abomasum of dairy cattle, yellow cattle, and three yak herds (WQ yak, SZ yak, and ZB yak) lived in different altitude, based on sequencing the bacterial 16S rRNA gene on Illumina Miseq. The bacterial diversity was significantly different among five breeds, whereas the difference among four stomach regions is limited. The phyla Bacteroidetes and Firmicutes were the dominated bacteria regardless of breeds and regions. The nonmetric multidimensional scaling (NMDS) results showed that the microbiota in dairy cattle, yellow cattle and WQ yak significantly differed from that in SZ yak and ZB yak for all four stomach compartments. Canonical correlation analysis revealed that Prevotella and Succiniclasticum spp. were abundant in dairy cattle, yellow cattle and WQ yak, whereas the Christensenellaceae R7 group and the Lachnospiraceae UCG 008 group were prevalent in SZ yak and ZB yak. Moreover, the microbiota in WQ yak was significantly different from that in SZ yak and ZB yak, which were characterized by the higher relative abundance Romboutsia spp., Eubacterium coprostanoligenes, Acetobacter spp., Mycoplasma spp., and Rikenellaceae RC9 group. Overall, these results improves our knowledge about the GIT microbiota composition of QTP ruminant.

Transcriptome profiles revealed the mechanisms underlying the adaptation of yak to high-altitude environments.

The yak is a valuable species in the Qinghai-Tibet Plateau of China. Nevertheless, the molecular mechanisms underlying its adaptation to high-altitude environments remain largely unknown. In the present study, comparative transcriptome sequencing was performed for lung and gluteus tissues from two species of low-altitude cattle (Sanjiang and Holstein cattle), Tibetan cattle (living at a moderate altitude), and yak (living at a high altitude) and the differentially expressed genes were validated using real-time quantitative PCR. The results showed that CD36 antigen was up-regulated and CD59 antigen was down-regulated in yak in comparison to the other animals, which might promote the development of red blood cells and inhibit the development of lymphocytes in yak. In addition, thrombospondin type 1, coagulation factor 5/8, and fibronectin were all down-regulated, but serpin and alpha 2-macroglobulin (A2M) were up-regulated. These differences would inhibit blood coagulation, thus reducing the risk of pulmonary edema. The expression levels of the calcium-release, potassium, and transient receptor potential channels decreased in yak, minimizing membrane depolarization and the harmful effects of pulmonary edema. Eleven KEGG pathways associated with innate immunity were more activated in yak and Tibetan cattle than in other cattle strains, which should reduce their risk of infection and disease. These changes together might facilitate the adaptation of yak and Tibetan cattle to live in high-altitude habitats.