Fat tail is one of the most important domesticated characteristics in sheep; however its molecular mechanism is poorly understood. Here we took small-tailed F2 hybrid of wild Argali sheep and typical fat-tailed Bashby sheep as research object. First, histological analysis revealed that the mean diameter and area in tail and subcutaneous fat cells, and surface density in tail fat in Bashby sheep were significantly larger than that in F2 sheep, and surface density of fat in subcutaneous fat in Bashby sheep was significantly lower than that in F2 sheep. Second, 873 differentially expressed genes (DEGs) of tail fat between Bashby and F2 sheep were identified by RNA-seq. Third, the tissue expression profile and relative expression difference between Bashby and F2 sheep of 7 of 873 DEGs were analyzed by RT-PCR. SCD, ESR1, EMR1, PHYH, STAT3 and GPAM genes were highly expressed in fat, muscle and liver, and ALDH1A1 were highly expressed in small intestine. In addition, the expressions of SCD, PHYH and CPAM genes in tail fat of F2 sheep were lower than that of Bashby sheep, while the expression patterns of ESR1 and EMR1 were reversed. Our findings will not only help understand molecular mechanism of fat tail, but also provide theoretical material in sheep evolution.

DNA methylation is a form of epigenetic regulation, having pivotal parts in controlling cellular expansion and expression levels within genes. Although blood DNA methylation has been studied in humans and other species, its prominence in cattle is largely unknown. This study aimed to methodically probe the genomic methylation map of Xinjiang brown (XJB) cattle suffering from bovine respiratory disease (BRD), consequently widening cattle blood methylome ranges. Genome-wide DNA methylation profiling of the XJB blood was investigated through whole-genome bisulfite sequencing (WGBS). Many differentially methylated regions (DMRs) obtained by comparing the cases and controls groups were found within the CG, CHG, and CHH (where H is A, T, or C) sequences (16,765, 7502, and 2656, respectively), encompassing 4334 differentially methylated genes (DMGs). Furthermore, GO/KEGG analyses showed that some DMGs were involved within immune response pathways. Combining WGBS-Seq data and existing RNA-Seq data, we identified 71 significantly differentially methylated (DMGs) and expressed (DEGs) genes (p < 0.05). Next, complementary analyses identified nine DMGs (LTA, STAT3, IKBKG, IRAK1, NOD2, TLR2, TNFRSF1A, and IKBKB) that might be involved in the immune response of XJB cattle infected with respiratory diseases. Although further investigations are needed to confirm their exact implication in the involved immune processes, these genes could potentially be used for a marker-assisted selection of animals resistant to BRD. This study also provides new knowledge regarding epigenetic control for the bovine respiratory immune process.

Bovine respiratory disease (BRD) is one of the major health issues in the cattle industry, resulting in significant financial crises globally. There is currently no good treatment, and cattle are made resistant to pneumonia through disease-resistant breeding. The serial blood samples from six Xinjiang brown (XJB) calves were collected for the RNA sequencing (RNA-seq). The obtained six samples were grouped into two groups, in each group as infected with BRD and healthy calves, respectively. In our study, the differential expression mRNAs were detected by using RNA-seq and constructed a protein–protein interaction (PPI) network related to the immunity in cattle. The key genes were identified by protein interaction network analysis, and the results from RNA-seq were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 488 differentially expressed (DE) mRNAs were identified. Importantly, the enrichment analysis of these identified DEGs classified them as mainly enriched in the regulation and immune response processes. The 16 hub genes were found to be related to immune pathways categorized by PPIs analysis. Results revealed that many hub genes were related to the immune response to respiratory disease. These results will provide the basis for a better understanding of the molecular mechanism of bovine resistance to BRD.

Natural or artificial selection causes animals to adapt to their environment. The adaptive changes generated by the rumen population and metabolism form the basis of ruminant evolution. In particular, the adaptive drive for environmental adaptation reflects the high-quality traits of sheep that have migrated from other places or have been distant from their origins for a long time. The Hu sheep is the most representative sheep breed in the humid and low-altitude environments (Tai Lake region) in East Asia and has been widely introduced into the arid and high-altitude environments (Tibetan Plateau and Hotan region), resulting in environmental adaptive changes in the Hu sheep. In this study, a joint analysis of the rumen microbial metagenome and metabolome was conducted on Hu sheep from different regions (area of origin and area of introduction) with the objective of investigating the quality traits of Hu sheep and identifying microorganisms that influence the adaptive drive of ruminants. The results demonstrated that the growth performance of Hu sheep was altered due to changes in rumen tissue and metabolism following their introduction to the arid area at relatively high altitude. Metagenomic and metabolomic analyses (five ramsper area) revealed that 3580 different microorganisms and 732 different metabolites were identified in the rumen fluid of arid sheep. Among these, the representative upregulated metabolites were 4,6-isocanedione, methanesulfonic acid and N2-succinyl-L-arginine, while the dominant microorganism was Prevotella ruminicola. The downregulated metabolites were identified as campesterol, teprenone and dihydroclavaminic acid, while the disadvantaged microorganisms were Dialister_succinatiphilus, Prevotella_sp._AGR2160, Prevotella_multisaccharivorax and Selenomonas_bovis. The results of the Pearson analysis indicated that the rumen microbiota and metabolite content of sheep were significantly altered and highly correlated following their relocation from a humid lowland to an arid upland. In particular, the observed changes in rumen microorganisms led to an acceleration of body metabolism, rendering sheep highly adaptable to environmental stress. Prevotella_ruminicola was identified as playing an important role in this process. These findings provide insights into the environmental adaptation mechanisms of sheep.

This study aimed to identify phenotypic biomarkers associated with high-altitude adaptation in Bayinbuluke sheep and to investigate the correlations between serum biochemical parameters and muscle transcriptomic, metabolomic, and proteomic profiles. Bayinbuluke sheep (raised at 3200 m) and Turpan black sheep (raised at−154 m) were selected for the experiment. The results demonstrated that, to adapt to the complex high-altitude hypoxic environment, Bayinbuluke sheep enhance glycolytic flux to rapidly generate energy, suppress intramuscular lipid synthesis, regulate lipid metabolic homeostasis to maintain energy balance, and remodel metabolic networks. Specifically, the GPAT3 gene promotes neutral cholesterol ester hydrolase 1 (NCEH1) through the glycerophospholipid metabolism pathway, facilitating the hydrolysis of cholesterol esters and fatty acid esters, thereby modulating systemic lipid metabolism. The FASN gene regulates energy metabolism via the AMPK signaling pathway, increasing the levels of glycolytic intermediates and markers such as nicotinamide adenine dinucleotide (NAD). Meanwhile, L-lactate dehydrogenase (LDHB) enhances the glycolytic process under hypoxic conditions through the HIF-1 signaling pathway, catalyzing the conversion between lactate and pyruvate in muscle tissue to produce energy, thereby supporting energy supply under high-altitude hypoxia. Additionally, the GSTA1 gene improves detoxification capability and antioxidant responses through the drug metabolism—other enzymes system, alleviating oxidative stress damage. This study systematically elucidates the molecular regulatory network underlying high-altitude adaptation in Bayinbuluke sheep, providing a theoretical foundation for enhancing the genetic adaptability of livestock resources in high-altitude environments.