The Tibetan sheep is an indigenous species of the Tibetan plateau and has been well adapted to high-altitude hypoxia. In comparison to lowland sheep breeds, the blood gas indicators have changed and the HIFs signaling pathway is activated in Tibetan sheep. These phenotypic and genetic alterations in Tibetan sheep are thought to be an important basis for adaptation to high-altitude hypoxia and variation in genes encoding the subunits that make up HIFs, such as HIF-1α can affect blood gas indicators. In this study, exons 9, 10, 12 of the HIF-1α gene were sequenced to find variations and 3 SNPs were detected, and these 3 SNPs were genotyped by KASP in 341 Hu sheep and 391 Tibetan sheep. In addition, 197 Hu sheep, 160 Tibetan sheep and 12 Gansu alpine merino sheep were used for blood gas indicators analysis. The results showed significant differences between the blood gas indicators of high-altitude breeds (Tibetan sheep and Gansu alpine merino sheep) and low-altitude breeds (Hu sheep), implying that the differences in blood gas indicators are mainly caused by differences in altitude. The haplotype combinations H2H3 and H1H3 were more frequent in the Tibetan sheep population, H2H3 increases O₂ carrying capacity by increasing hematocrit and hemoglobin concentrations; H1H3 makes O₂ dissociate more readily from oxyhemoglobin by decreasing partial pressure of oxygen and oxygen saturation. These results suggest that variants at the HIF-1α promote the ability of oxygen utilization in Tibetan sheep, which may underpin the survival and reproduction of Tibetan sheep on the Tibetan plateau.

The enzyme long-chain acyl-CoA synthetase 1 (ACSL1) is essential for lipid metabolism. The ACSL1 gene controls unsaturated fatty acid (UFA) synthesis as well as the formation of lipid droplets in bovine adipocytes. Here, we used RNA-Seq to determine lncRNA and mRNA that regulate UFA synthesis in bovine adipocytes using RNA interference and non-interference with ACSL1. The corresponding target genes of differentially expressed (DE) lncRNAs and the DE mRNAs were found to be enriched in lipid and FA metabolism-related pathways, according to GO and KEGG analyses. The differentially expressed lncRNA- differentially expressed mRNA (DEL-DEM) interaction network indicated that some DELs, such as TCONS_00069661, TCONS_00040771, TCONS_ 00035606, TCONS_00048301, TCONS_001309018, and TCONS_00122946, were critical for UFA synthesis. These findings assist our understanding of the regulation of UFA synthesis by lncRNAs and mRNAs in bovine adipocytes.

The Tibetan sheep is an indigenous animal of the Tibetan plateau, and after a long period of adaptation have adapted to high-altitude hypoxia. Many physiological changes occur in Tibetan sheep as they adapt to high-altitude hypoxia, especially in the lungs. To reveal the physiological changes and their molecular mechanisms in the lungs of Tibetan sheep during adaptation to high altitudes, we selected Tibetan sheep from three altitudes (2500 m, 3500 m, and 4500 m) and measured blood-gas indicators, observed lung structures, and compared lung proteome changes. The results showed that the Tibetan sheep increased their O₂-carrying capacity by increasing the hemoglobin (Hb) concentration and Hematocrit (Hct) at an altitude of 3500 m. While at altitude of 4500 m, Tibetan sheep decreased their Hb concentration and Hct to avoid pulmonary hypertension and increased the efficiency of air-blood exchange and O₂ transfer by increasing the surface area of gas exchange and half-saturation oxygen partial pressure. Besides these, some important proteins and pathways related to gas transport, oxidative stress, and angiogenesis identified by proteome sequencing further support these physiology findings, including HBB, PRDX2, GPX1, GSTA1, COL14A1, and LTBP4, etc. In conclusion, the lungs of Tibetan sheep are adapted to different altitudes by different strategies; these findings are valuable for understanding the basis of hypoxic adaptation in Tibetan sheep.

Fatty acid synthase (FASN) is an enzyme involved in the synthesis of fatty acids (FA) and plays a central role in de novo lipogenesis in mammals. This study was conducted to ascertain the relative level of expression of the FASN gene (FASN) in tissues from the yak (Bos grunniens), and to search for variation in two regions of yak FASN using polymerase chain reaction single-stranded conformational polymorphism (PCR-SSCP) analyses; it also ascertains whether that variation is associated with yak milk traits. The gene was found to be expressed in twelve tissues, with the highest expression detected in the mammary gland, followed by subcutaneous fat tissue. Two regions of the gene were analyzed in 290 Gannan yaks: A region spanning exon 24-intron 24 and a region spanning exon 34. These regions both produced two PCR-SSCP patterns, which, upon sequencing, represented different DNA sequences. This sequence variation resulted from the presence of three nucleotide substitutions: c.4296+38C/T (intron 24), c.5884A/G, and c.5903G/A, both located in exon 34. The exon 34 substitutions would result in the amino acid substitutions p.Thr1962Ala and p.Gly1968Glu if expressed. Four haplotypes spanning from the exon 24-intron 24 region to exon 34 were identified. Of these, two were common (A₁-A₂ and B₁-A₂), and two were rare (A₁-B₂ and B₁-B₂) in the yaks investigated. The presence of A₁-A₂ was associated with an increase in milk fat content (p = 0.050) and total milk solid content (p = 0.037), while diplotype A₁-A₂/B₁-A₂ had a higher milk fat content (p = 0.038) than the other diplotypes. This study suggests that further characterization of the FASN gene might provide for an improved understanding of milk traits in yaks.

Plateau adaptation in animals involves genetic mechanisms as well as coevolutionary mechanisms of the microbiota and metabolome of the animal. Therefore, the characteristics of the rumen microbiome and metabolome, transcriptome, and serum metabolome of Tibetan sheep at different altitudes (4500 m, 3500 m, and 2500 m) were analyzed. The results showed that the rumen differential metabolites at 3500 m and 4500 m were mainly enriched in amino acid metabolism, lipid metabolism, and carbohydrate metabolism, and there was a significant correlation with microbiota. The differentially expressed genes and metabolites at middle and high altitudes were coenriched in asthma, arachidonic acid metabolism, and butanoate and propanoate metabolism. In addition, the serum differential metabolites at 3500 m and 4500 m were mainly enriched in amino acid metabolism, lipid metabolism, and metabolism of xenobiotics by cytochrome P450, and they were also related to microbiota. Further analysis revealed that rumen metabolites accounted for 7.65% of serum metabolites. These common metabolites were mainly enriched in metabolic pathways and were significantly correlated with host genes (p < 0.05). This study found that microbiota, metabolites, and epithelial genes were coenriched in pathways related to lipid metabolism, energy metabolism, and immune metabolism, which may be involved in the regulation of Tibetan sheep adaptation to plateau environmental changes.