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Long-haired individuals in the Tianzhu white yak population are a unique genetic resource, and have important landscape value. Copy number variation (CNV) is an important source of phenotypic variation in mammals. In this study, we used resequencing technology to detect the whole genome of 10 long-haired Tianzhu white yaks (LTWY) and 10 normal-haired Tianzhu white yaks (NTWY), and analyzed the differences of CNV in the genome of LTWYs and NTWYs. A total of 110268 CNVs were identified, 2006 CNVRs were defined, and the distribution map of these CNVRs on chromosomes was constructed. The comparison of LTWYs and NTWYs identified 80 differential CNVR-harbored genes, which were enriched in lipid metabolism, cell migration and other functions. Notably, some differential genes were identified as associated with hair growth and hair-follicle development (e.g., ASTN2, ATM, COL22A1, GK5, SLIT3, PM20D1, and SGCZ). In general, we present the first genome-wide analysis of CNV in LTWYs and NTWYs. Our results can provide new insights into the phenotypic variation of different hair lengths in Tianzhu white yaks. [ABSTRACT FROM AUTHOR]

Simple Summary: Ashidan yak is a new breed of hornless yak developed by Chinese scientists, which has an important economic value. However, little is known about the growth of Ashidan yaks. This study analyzed the body weight and body size measurements of 260 female Ashdan yaks and compared the performance of five nonlinear models (Logistic model, Gompertz model, Brody model, von Bertalanffy model and Richards model). Our results showed that the early growth and development of Ashidan yak change with the seasons, and the Richards model performs better among the five models. Understanding animal growth plays an important role in improving animal genetics and breeding. In order to explore the early growth and development law of Ashidan yak, the body weight (BW), wither height (WH), body oblique length (BL) and chest girth (CG) of 260 female Ashidan yaks were measured. These individuals grew under grazing conditions, and growth traits were measured at 6, 12, 18 and 30 months of age. Then the absolute growth and relative growth of Ashidan yak were calculated, and five nonlinear models (Logistic model, Gompertz model, Brody model, von Bertalanffy model and Richards model) were used to fit the growth curve of Ashidan yak. The fitting effect of the model was evaluated according to MSE, AIC and BIC. The results showed that the growth rate of Ashidan yak was the fastest from 12 to 18 months old, and the growth was slow or even stagnant from 6 to 12 months old. The AIC and BIC values of the Richards model were the lowest among the five models, with an AIC value of 4543.98 and a BIC value of 4563.19. The Richards model estimated body weight at 155.642 kg. In summary, the growth rate of female Ashidan yak changes with the seasons, growing faster in warm seasons and slower in cold seasons. Richards model is the best model to describe the growth curve of female Ashidan yak in five nonlinear models. [ABSTRACT FROM AUTHOR]

• This is the first systematic study of the keratin family in yak. 53 keratins are identified in yak. • The results show that yak keratins have the same conserved domain and sequence as other species keratins. • The study demonstrates the expression pattern of keratins genes throughout the hair cycle and identifies five different expression patterns. • Nine hub keratin genes are identified by WGCNA method in the whole hair cycle. As the largest subgroup of intermediate filament proteins, keratins are divided into two types of subfamily. Currently, the molecular mechanism of keratins in several animals has been reported but is limited in yak. Here, 53 different kinds of keratins were identified in the yak genome, including 23 type I and 30 type II keratins. Bioinformatics analysis in this study revealed that multiple phosphorylation sites were identified among all the family members. And the subcellular localization of these proteins was predicted to be in the nucleus, cytoskeleton, and cytoplasm. All keratin family proteins were unstable and the scores of instability coefficient were higher than 40. Phylogenetic analysis showed that high consistency results of the sequence conservation and grouping were found in the genomes of yak, sheep, cattle, mouse, rat, and human. Based on the expression patterns obtained from the transcriptome data, keratin genes (KRTs) were grouped into five clusters, and results also showed that KRTs were highly activated in skin tissues during the hair cycle in yak. Among the five clusters, Cluster II contained the most KRTs , which was the main expression pattern of the yak hair follicle cycle, followed by Cluster III. These results indicated the transition period from telogen to anagen and catagen to telogen were highly dynamic in yak. Gene expression correlation analysis showed that KRTs exhibited a strong correlation (mainly positive correlation) throughout the hair follicle development cycle. And the identification of hub KRTs in specific modules related to hair follicle development in this study was performed using the Weight Gene Co-Expression Network Analysis (WGCNA). Specific modules that include KRTs were darkgreen (KRT40), darkgrey (KRT5), turquoise (KRT1 , KRT2 , KRT10), bisque4 (KRT4), thistle2 (KRT9 , KRT39), and yellowgreen (KRT24). The interaction network showed that these genes were found to be related to the regulation of cell cycle, melanogenesis, hair follicle development, keratinocyte proliferation. Our study provides theoretical support for the study of the evolutionary relationship and molecular mechanism of keratin family in B. grunnien. [ABSTRACT FROM AUTHOR]

Although significant advancement has been made in the study of adipogenesis, knowledge about how chromatin accessibility regulates yak adipogenesis is lacking. We here described genome-wide dynamic chromatin accessibility in preadipocytes and adipocytes by using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), and thus revealed the unique characteristics of open chromatin during yak adipocyte differentiation. The chromatin accessibility of preadipocytes and adipocytes exhibited a similar genomic distribution, displaying a preferential location within the intergenic region, intron, and promoter. The pathway enrichment analysis identified that genes with differential chromatin accessibility were involved in adipogenic metabolism regulation pathways, such as the peroxisome proliferator activated receptor-γ (PPAR) signaling pathway, wingless-type MMTV integration site (Wnt) signaling pathway, and extracellular matrix-receptor (ECM–receptor) interaction. Integration of ATAC-seq and mRNA-seq revealed that genes with a high expression were associated with high levels of chromatin accessibility, especially within 1 kb upstream and downstream of the transcription start site. In addition, we identified a series of transcription factors (TFs) related to adipogenesis and created the TF regulatory network, providing the possible interactions between TFs during yak adipogenesis. This study is crucial for advancing the understanding of transcriptional regulatory mechanisms of adipogenesis and provides valuable information for understanding the adaptation of plateau species to high-altitude environments by maintaining whole body homeostasis through fat metabolism. [ABSTRACT FROM AUTHOR]

Simple Summary: As a domestic animal living in the Qinghai-Tibet Plateau at high altitudes from 2000 to 5000 m, the growth rate of the yak is slow under extremely harsh natural environmental conditions, such as high altitude, low temperatures, and low oxygen. Compared with conventional selection, using molecular markers in breeding to improve yak growth traits is more efficient. Many studies have indicated that CNV mutations can significantly affect the phenotypic traits of livestock and poultry. This study explored the association between the growth traits and CNVs of SOX5 and SOX8 in 326 Ashidan yaks. Our results showed that CNVs and the CNV combination of SOX5 and SOX8 were significantly associated with withers height and chest girth (p < 0.05), suggesting these mutations could be new markers for the selection of yak growth traits. Copy number variation (CNV) is a structural variant with significant impact on genetic diversity. CNV has been widely used in breeding for growth traits, meat production or quality, and coat color. SRY-like box genes (SOXs) are a class of transcription factors that play a regulatory role in cell fate specification and differentiation. SOX5 and SOX8 belong to subgroups D and E of the SOXs, respectively. Previous studies have shown that SOX5 and SOX8 are essential in the development of bones. In this study, we explored the association between the growth traits and CNVs of SOX5 and SOX8 in 326 Ashidan yaks and detected mRNA expression levels in different tissues. Our results illustrated that CNVs of SOX5 and SOX8 were significantly associated with withers height at 18 months of age and chest girth at 30 months of age (p < 0.05). The CNV combination of SOX5 and SOX8 was significantly associated with withers height at 18 months of age (p < 0.01). SOX5 expression in the lung was significantly higher than in the heart, spleen, kidney, and muscle (p < 0.05). SOX8 expression in the lung was significantly higher than in the liver and muscle (p < 0.05). Our results provide evidence that the CNVs of SOX5 and SOX8 genes could be used as new markers for the selection of yak growth traits. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNA (lncRNA) as an important regulator has been demonstrated playing an indispensable role in the biological process of hair follicles (HFs) growth. However, their function and expression profile in the HFs cycle of yak are yet unknown. Only a few functional lncRNAs have been identified, partly due to the low sequence conservation and lack of identified conserved properties in lncRNAs. Here, lncRNA-seq was employed to detect the expression profile of lncRNAs during the HFs cycle of yak, and the sequence conservation of two datasets between yak and cashmere goat during the HFs cycle was analyzed. Results: A total of 2884 lncRNAs were identified in 5 phases (Jan., Mar., Jun., Aug., and Oct.) during the HFs cycle of yak. Then, differential expression analysis between 3 phases (Jan., Mar., and Oct.) was performed, revealing that 198 differentially expressed lncRNAs (DELs) were obtained in the Oct.-vs-Jan. group, 280 DELs were obtained in the Jan.-vs-Mar. group, and 340 DELs were obtained in the Mar.-vs-Oct. group. Subsequently, the nearest genes of lncRNAs were searched as the potential target genes and used to explore the function of DELs by GO and KEGG enrichment analysis. Several critical pathways involved in HFs development such as Wnt signaling pathway, VEGF signaling pathway, and signaling pathways regulating pluripotency of stem cells, were enriched. To further screen key lncRNAs influencing the HFs cycle, 24 DELs with differ degree of sequence conservation were obtained via a comparative analysis of partial DELs with previously published lncRNA-seq data of cashmere goat in the HFs cycle using NCBI BLAST-2.9.0+, and 3 DELs of them were randomly selected for further detailed analysis of the sequence conservation properties. Conclusions: This study revealed the expression pattern and potential function of lncRNAs during HFs cycle of yak, which would expand the knowledge about the role of lncRNAs in the HFs cycle. The findings related to sequence conservation properties of lncRNAs in the HFs cycle between the two species may provide valuable insights into the study of lncRNA functionality and mechanism. [ABSTRACT FROM AUTHOR]

Simple Summary: Yak is the dominant animal species in China's plateau regions. The development of the yak industry is conducive to protecting the ecosystem of the Qinghai–Tibet Plateau and promoting local economic development. However, the slow growth and development of yak have seriously affected the development of the yak industry. Structural variation (SV) has been widely applied in livestock breeding for growth traits. Therefore, it is of great significance to use SV to improve yak growth traits in yak breeding. Meanwhile, the GHR gene plays an important role in the formation and normal development of bones. This study associated the correlation between the yak GHR SV gene and growth traits and confirmed that GHR-SV can be used as a molecular marker for the early reproduction of yaks. This study provides a theoretical basis for the early growth and development of yaks. The growth hormone receptor (GHR) is a member of the cytokine/hematopoietic factor receptor superfamily, which plays an important role in the growth and development, immunity, and metabolism of animals. This study identified a 246 bp deletion variant in the intronic region of the GHR gene, and three genotypes, including type II, type ID, and type DD, were observed. Genotype analysis of structural variation (SV) was performed on 585 individuals from 14 yak breeds, and it was found that 246 bp deletion was present in each breed. The II genotype was dominant in all yak breeds except for SB yak. The association analysis of gene polymorphisms and growth traits in the ASD yak population showed that the 246 bp SV was significantly associated with body length at 6 months (p < 0.05). GHR messenger RNA (mRNA) was expressed in all the tested tissues, with significantly higher levels in the liver, muscle, and fat than in other organs. The results of transcription activity showed that the luciferase activity of the pGL4.10-DD vector was significantly higher than that of the pGL4.10-II vector (p < 0.05). Additionally, the transcription-factor binding prediction results showed that the SV in the runt-related transcription factor 1 (Runx1) transcription-factor binding site may affect the transcriptional activity of the GHR gene, regulating yak growth and development. This study showed that the novel SV of the GHR gene could be used as a candidate molecular marker for the selection of the early growth trait in ASD yak. [ABSTRACT FROM AUTHOR]

In mammals, epigenetic modifications involving DNA methylation are necessary for the completion of the cell differentiation process. However, the global DNA methylation landscape and its dynamics during yak adipocyte differentiation remain unexplored. Here, we performed whole-genome bisulfite sequencing (WGBS) to asses DNA methylation in yak preadipocytes and adipocytes, combining these results with those of our previous studies on changes in chromatin accessibility and gene expression during yak adipogenesis. The results showed that CG methylation levels were lower in promoter than in exon and intron, and gradually decreasing from the distal regions to transcription start site (TSS). There was a significant negative correlation between CG methylation levels located in promoter and gene expression levels. The 46 genes shared by CG differentially methylated regions (DMRs) and differential chromatin accessibility were significantly enriched in Hedgehog and PI3K-Akt signaling pathways. ATAC-seq peaks with high chromatin accessibility located in both promoter (≤ 2 kb from TSS) and distal (> 2 kb from TSS) regions corresponded to low methylation levels. Taken together, these findings demonstrated that DNA methylation and its interactions with chromatin accessibility regulate gene expression during yak adipocyte differentiation, contributing to the understanding of mechanisms of various epigenetic modifications and their interactions in adipogenesis. [ABSTRACT FROM AUTHOR]