Super enhancers (SEs) are crucial regulatory elements in the genome that determine cell identity and fate commitment through mechanisms such as recruiting transcription factors (TFs), interacting with super enhancers RNAs (seRNAs), and phase separation. This ensures accurate gene expression in response to both environmental and intrinsic signals. Advances in 3D genome architecture have further illuminated how SEs are organized and regulated within the nucleus, thereby enhancing our understanding of their function. Recent innovations in genomic technologies, including chromatin accessibility, CRISPR-Cas9, 3 C-based methods and imaging methods, have revolutionized the study of SEs. These technologies have facilitated precise mapping and functional characterization, providing deeper insights into how SEs influence gene regulation. In particular, these advancements offer promising potential for exploring SE dynamics in livestock improvement, opening avenues for the enhancement of agricultural and breeding practices. An integrated overview of super-enhancer mechanisms, research technologies, and applications in livestock breeding.
Neuropeptide B/W receptor-2 (NPBWR2) is a G protein-coupled receptor which is related to the regulation of feeding behavior, energy homeostasis, neuroendocrine function, and inflammatory pain. In addition, it plays a potential role in the regulation of stress, emotion, anxiety and fear responses. Interestingly, previous genomic analyses revealed variable levels of Bos javanicus introgression into Chinese indicine cattle, including a key adaptive region encompassing the NPBWR2 gene. By integrating introgression analysis with the Bovine Genome Variation Database, a banteng introgressed missense mutation (NC_083880.1: c.14C > G,Thr5Ser) of NPBWR2 was identified. The current study explored the allele frequency of this mutation in 1648 individuals representing 63 Chinese cattle breeds/populations using polymerase chain reaction amplification and whole genome resequencing methods. Here, we explored the prevalence of this variant in native Chinese cattle to instigate the introgression influence of B. javanicus on Chinese cattle.
Many factors affect bovine skeletal muscle development, among which noncoding RNAs are very important. While circular RNAs (circRNAs) play a central role in various physiological and pathological processes, their potential role in muscle development is poorly understood. Here, we identified several differentially expressed circRNAs in fetal and adult skeletal muscle tissue sequencing data. They included a circRNA originating from exon 24 circularization of the myosin heavy chain protein 8 gene (MYH8), circMYH8, which was significantly downregulated in the adult muscle tissue. We examined circMYH8’s role in skeletal muscle cell proliferation, apoptosis, and differentiation through its overexpression or inhibition. Specifically, we used luciferase reporter gene assays, western blots, real-time reverse transcription quantitative PCR, cell counting kit 8, and 5-ethynyl-2-deoxyuridine to explore circMYH8’s molecular sponge effect on bovine myoblast proliferation, apoptosis, and differentiation via competitively binding microRNA 221 to activate cyclin-dependent kinase inhibitor 1B. Then, we investigated circMYH8’s role in promoting muscle regeneration by injecting a circMYH8 overexpression plasmid into muscle-injured mice. The results suggest that circMYH8 inhibits bovine myoblast proliferation and facilitates cell apoptosis and differentiation acts through the miR-221/P27 axis. This study shows that circMYH8 is a potential myogenesis-related factor and provides new evidence for elucidating complex molecular mechanisms and a better understanding of the function of mammalian circular RNAs in muscle development.
Circular RNAs (circRNAs) have emerged as critical regulators of skeletal muscle development, yet the functions of many muscle-derived circRNAs remain uncharacterized. In this study, we identified a novel circRNA, circAIDA, formed by exons 2 to 6 of the AIDA gene, based on bovine muscle sequencing data. Mechanistically, we demonstrate that circAIDA acts as a molecular sponge for miR-29a, thereby relieving the repression of its downstream targets, AKT3 and CLCN2. Functionally, circAIDA promotes bovine myoblast proliferation while inhibiting apoptosis and differentiation in vitro. Furthermore, experiments in vivo suggested circAIDA could attenuate regeneration of skeletal muscle in mice. In brief, we discovered a novel circAIDA/miR-29a interaction that regulates bovine myogenesis, providing new insights into the molecular networks controlling skeletal muscle development.
This experiment aimed to investigate the variation patterns of seed morphology and germination characteristics of rye from different provenances. A total of 25 local rye germplasm accessions from Yunnan Province and 11 germplasm accessions from other provinces were used as materials. Morphological indicators including seed length, seed width, embryo length, length-width ratio, and thousand-seed weight, as well as germination indicators including germination rate, germination potential, and germination index, were measured and comprehensively evaluated using the membership function method. The results showed that there were differences in seed morphology and germination characteristics among rye from different provenances. The povincial germplasm generally exhibited an elongated shape, while the introduced varieties presented a plump shape. The average thousand-seed weight of rye from other provinces was 29.81% higher than that of the povincial materials. Correlation analysis indicated that thousand-seed weight was extremely correlated with seed length, seed width, and embryo length (P<0.01). Germination rate, germination potential, and germination index were significantly or extremely correlated with embryo length (P<0.05 or P<0.01). The study shows that there are morphological differences between rye germplasm within Yunnan Province and those from other provinces. Based on the comprehensive morphology and germination characteristics, the rye material from the Zhaotong area has a better overall evaluation.
Yunnan Province, located in Southwestern China, the intricate geography, variable climate, and abundant vegetation of the region have collectively contributed to shaping the distinctive germplasm characteristics observed in Yunnan indigenous cattle through prolonged domestication. The different breeds of Yunnan cattle exhibit distinct advantageous characteristics and traits, which are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and tough feeding conditions. However, a comprehensive genomic landscape of genetic resources has yet to be delineated. Herein, we employed 140 whole-genome sequencing data from Yunnan indigenous cattle across eight breeds to elucidate their genetic diversity and population structure. Utilizing both uniparental and biparental markers, we elucidated the intricate genetic composition of Yunnan indigenous cattle, which is closely correlated with the geographic environment. A predominant East Asian indicine ancestry which gradually diminishes towards the north. The analysis revealed a high genetic diversity among populations and a low-to-moderate inbreeding coefficient, underscoring the rich genetic reservoir of Yunnan cattle breeds. Additionally, gene flow between Yunnan indicine and wild Bos species in and around Yunnan was verified, highlighting localized introgression from Yunnan Gayal as a critical factor in the successful adaptation of Yunnan indicine cattle to the local hot and humid environments. Our findings established the SNPs database for facilitating resource conservation and selective breeding. Moreover, these valuable insights into the genomic diversity and adaptive history of Yunnan indigenous cattle breeds contribute significantly to our understanding of their evolutionary dynamics and offer a foundation for future genetic improvement and conservation strategies.
Gayal (Bos frontalis) an endangered bovine species inhabitingChina, India, Bangladesh, Myanmar and Bhutan, has a mysterious evolutionary origin. Shaped by natural selection, its unique traits make it a valuable genetic resource; however, its populations are rapidly declining. In this study, comprehensive whole-genome resequencing of fifty-eight samples of Gayal from China, India, Myanmar and Bangladesh was performed. We identified over 44 million SNPs across four Gayal populations. Nucleotide diversity analysis revealed variations in genetic diversity, with the lowest occurring in India and the highest occurring in China. Phylogenetic tree analysis revealed three distinct clades representing China, India and Bangladesh-Myanmar, which were further confirmed by principal component and admixture analyses. The genetic exchanges between Gayal and other bovine species indicate limited influence from domestic cattle in both the Chinese and Bangladeshi Gayal populations. Mitochondrial DNA sequences and a phylogenetic tree highlighted the unique mitochondrial genome of Gayal. Genome-wide selection signals pinpointed candidate genes linked to mitochondrial function, immunity, musculoskeletal development, reproduction and growth performance. Distinct haplotype patterns emerged for the CCDC157, KIAA0753 and MTFP1 genes in the Chinese and Bangladesh-Myanmar Gayal populations, indicating artificial selection in the Chinese population. KEGG pathway and gene ontology enrichment analyses provided insights into processes related to neurodevelopment, cardiac function, tissue growth, immunity and metabolism. In summary, our study enhances our understanding of Gayal genetics, population structure and selection signals across four countries. This knowledge is crucial for conserving this endangered species amid its rapid decline.
Hunan Province, located in Central-South China, has a hot and humid climate, which has shaped the unique characteristics of its cattle. In this study, we analyzed the genomic diversity of 110 indigenous Hunan cattle using whole-genome sequencing and found that they have a mixed ancestry of indicine and taurine. By grouping the cattle based on their collection regions (western, central, southeastern, and southern Hunan), we used an unsupervised three-component Gaussian model to classify the runs of homozygosity (ROH) and calculated the genomic inbreeding coefficient based on runs of homozygosity (FROH) to assess inbreeding levels. The results showed that western Hunan cattle had the highest level of hybridization, while southern Hunan cattle had the lowest. Through selective sweep analysis, we identified candidate genes and pathways related to environmental adaptation and homeostasis. Notably, the SLC5A2 gene showed strong selection signals across all four regions and exhibited a distinct haplotype compared to other referenced cattle breeds. Additionally, we detected introgression from wild species into Hunan domestic cattle and analyzed their Y-chromosome haplotypes.
N6-methyladenosine (m6A), a well-known post-transcriptional modification, is implicated in diverse cellular and physiological processes. However, much remains unknown regarding the precise role and mechanism of m6A modification on muscle development. In this study, we make observation that the levels of m6A and METTL3 are markedly elevated during the differentiation phase (DM) compared to the growth phase (GM) in both C2C12 and bovine myoblasts. Notably, deletion of METTL3 decreased m6A levels, and promoted myoblast proliferation, inhibited myoblast differentiation in vitro. By performing m6A sequencing in both GM and DM myoblast, we further identified that TM4SF1 is involved in m6A -regulated muscle development. Mechanistically, METTL3 increases m6A-modified TM4SF1 transcripts, and subsequently YTHDF2 promotes TM4SF1 mRNA degradation in P-body through liquid-liquid phase separation (LLPS). Additionally, the rescue experiments in vivo showed that overexpressing METTL3 could rescue the attenuated myogenesis induced by TM4SF1 overexpression during muscle regeneration in mice. Collectively, our findings shed light on a regulatory mechanism by which m6A modulates muscle development and raise a new model for m6A-mediated mRNA degradation within P-bodies.
Yajiangxue cattle (XF) is three-way crossbred cattle developed specifically for producing high-quality beef in the Tibetan Plateau by introducing the bloods of Tibetan yellow cattle (HF) and Angus cattle into Tibetan yak (MF). In the present study, we mainly focused on fat deposition and metabolism changes and used RNA-seq and LC-MS/MS-based metabolomics to partially explain the meat quality improvement in Yajiangxue cattle. Differential expression analysis revealed 1762, 2949, and 2931 different expression genes in XF vs. HF, XF vs. MF, and XF vs. cattle–yak (PF), respectively, such as BMP2, WISP2, FGF1, IL1B, IL6, and WNT5B. Immune response, oxidation–reduction processes, and fatty acid metabolism were markedly enriched. Furthermore, an initial identification revealed 319 metabolites using positive ion mode and 289 metabolites using negative ion mode in bovine adipose tissue across four breeds/populations. Of these, 143 were differential metabolites in positive ion mode, while 166 were in negative ion mode. The main pathways of metabolism affected by breed/population were unsaturated fatty acid biosynthesis, tryptophan and tyrosine biosynthesis, primary bile acid biosynthesis, cholesterol metabolism, beta-alanine metabolism, etc. Similarly, both the transcriptome and the metabolome results highlighted fatty acid metabolism. These results could help elucidate the biological mechanisms involved in fat deposition and identify valuable biomarkers for specific metabolite accumulation.
Structural variations (SVs) play crucial roles in the evolutionary adaptation of domesticated animals to natural and human-controlled environments, but SVs have not been explored in Tibetan cattle, which recently migrated and rapidly adapted to the high altitudes of the Qinghai-Tibetan Plateau (QTP). In this study, a de novo chromosome-level genome assembly for Tibetan cattle is constructed. It is found that using a lineage-specific reference genome significantly increased variant detection accuracy and completeness. Analysis of long-read sequencing data from 36 high-altitude QTP and 48 low-altitude cattle identified 222 528 SVs and 259 SV hotspot regions. Positively selected SVs in high-altitude cattle are related to energy metabolism erythropoiesis and angiogenesis, and peroxisomal metabolism. A 102-bp intronic deletion in GNPAT likely upregulated its expression. It is distinguished 7293 SVs that may be introgressed from yak, including variants upstream of the hypoxia-inducing gene EGLN1. Finally, a ≈2-Mb heterozygous inversion and two translocations on chromosome 6 are likely associated with the cattle gray coat via regulatory effects on the KIT gene. The results confirm the importance of SVs in evolutionary adaptation and the contribution yak-introgressed SVs to the rapid acclimatization of QTP cattle.
During the past 3000 years, cattle on the Qinghai-Xizang Plateau have developed adaptive phenotypes under the selective pressure of hypoxia, ultraviolet (UV) radiation, and extreme cold. The genetic mechanism underlying this rapid adaptation is not yet well understood. Here, we present whole-genome resequencing data for 258 cattle from 32 cattle breeds/populations, including 89 Tibetan cattle representing eight populations distributed at altitudes ranging from 3400 m to 4300 m. Our genomic analysis revealed that Tibetan cattle exhibited a continuous phylogeographic cline from the East Asian taurine to the South Asian indicine ancestries. We found that recently selected genes in Tibetan cattle were related to body size (HMGA2 and NCAPG) and energy expenditure (DUOXA2). We identified signals of sympatric introgression from yak into Tibetan cattle at different altitudes, covering 0.64%–3.26% of their genomes, which included introgressed genes responsible for hypoxia response (EGLN1), cold adaptation (LRP11), DNA damage repair (LATS1), and UV radiation resistance (GNPAT). We observed that introgressed yak alleles were associated with noncoding variants, including those in present EGLN1. In Tibetan cattle, three yak introgressed SNPs in the EGLN1 promoter region reduced the expression of EGLN1, suggesting that these genomic variants enhance hypoxia tolerance. Taken together, our results indicated complex adaptation processes in Tibetan cattle, where recently selected genes and introgressed yak alleles jointly facilitated rapid adaptation to high-altitude environments.
This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.
Cattle are sensitive to temperature fluctuations but adapt well to inclement weather conditions. When environmental temperatures exceed specific thresholds, heat stress becomes a critical concern for cattle. The TRPM2 gene, which resides on cattle chromosome 1 encodes a TRP channel protein, holding a unique capacity to sense temperature changes and facilitate rapid response to avoid heat stress. Here, we utilized the Bovine Genome Variation Database (BGVD) (http://animal.omics.pro/code/index.php/BosVar), and identified a missense mutation site, c.805A > G: p. Met269Val (rs527146862), within the TRPM2 gene. To elucidate the functional assessment of this mutation in temperature adaptation attributes of Chinese cattle, we genotyped 407 samples from 20 distinct breeds representing diverse climatic zones across China. The association analysis incorporates three temperature parameters and revealed compelling insights in terms of allele frequency. Interestingly, the prevalence of the wild-type allele A was notably higher among northern cattle breeds and this trend diminished gradually as observed in southern cattle populations. Conversely, the mutant-type allele G demonstrated a contrasting trend. Moreover, southern cattle exhibited markedly higher frequencies of GG and GA genotypes (P < 0.01). The presence of heterozygous and homozygous mutations appears to confer an enhanced capacity for adaptation to elevated temperatures. These results provide unequivocal correlation evidence between TRPM2 genotypes (AA, GA, GG) and environmental temperature parameters and comprehend the genetic mechanisms governing temperature adaptation in cattle. This provides valuable insights for strategic breed selection across diverse climatic regions, thereby aiding livestock production amid evolving climate challenges.
Context China has a vast area across many temperature zones and a variety of cattle breeds. These cattle resources are ideal models to research their adaptability to the environment. The KRT38 gene is an acidic protein, and its coding product can be used as a component of hair production. Aims The objective of this study was to investigate the diversity of the KRT38 gene in Chinese local cattle and the association of different genotypes with mean temperature, relative humidity and temperature humidity index. Methods A missense mutation g.41650738 A > G in the KRT38 gene was screened from the database of bovine genomic variation (BGVD) and was genotyped in a total of 246 samples from 15 local cattle breeds in China by polymerase chain reaction amplification and sequencing. Finally, the correlation between the locus and the three climatic factors was analysed. Key results We successfully obtained the frequency of this single-nucelotide polymorphism in three groups of cattle in northern, central and southern China. The frequency of allele A gradually declined from north to south, whereas the frequency of allele G showed the opposite trend with a clear geographic distribution. Conclusions Our results indicate that KRT38 variation in Chinese indigenous cattle might be linked to heat tolerance. Implications Our analysis may assist in determining the importance of the variation as a genetic signal for heat tolerance in cattle reproduction and genetics.
为了解文山牛的体重和体尺性状的生长发育规律,加强文山牛品种选育,进一步提高文山牛的生产性能,该研究随机选取30头文山牛母牛和10头文山牛公牛为试验对象,测定出生、断奶、6、12、18、24月龄和36月龄的体重和体尺指标.结果表明,文山牛公、母牛均为早期生长速度较快,24月龄后生长速度缓慢,相对生长速率总体上呈现下降的趋势;公、母牛体重在0~6月龄增长最快,从出生到断奶时体重、体高、十字部高、体斜长、胸围、腹围和管围相对生长速率最快,公、母牛18~24月龄属于役用型,36月龄属于役肉兼用型;除体斜长外,体重与其余性状均为极显著相关(P<0.01),文山牛公、母牛体斜长指数(公牛从断奶到6月龄除外)和胸围指数均随着年龄的增长而变大,而体躯指数分别在18月龄和36月龄达到顶峰,管围指数变化不明显.
Specific ecological environments and domestication have continuously influenced the physiological characteristics of Chinese indigenous cattle. Among them, Bashan cattle belongs to one of the indigenous breeds. However, the genomic diversity of Bashan cattle is still unknown. Published whole-genome sequencing (WGS) data of 13 Bashan cattle and 48 worldwide cattle were used to investigate the genetic composition and selection characteristics of Bashan cattle. The population structure analysis revealed that Bashan cattle harbored ancestries with East Asian taurine and Chinese indicine. Genetic diversity analysis implied the relatively high genomic diversity in Bashan cattle. Through the identification of containing >5 nsSNPs or frameshift mutations genes in Bashan cattle, a large number of pathways related to sensory perception were discovered. CLR, θπ ratio, FST, and XP-EHH methods were used to detect the candidate signatures of positive selection in Bashan cattle. Among the identified genes, most of the enriched signal pathways were related to environmental information processing, biological systems, and metabolism. We mainly reported genes related to the nervous system (HCN1, KATNA1, FSTL1, GRIK2, and CPLX2), immune (CD244, SLAMF1, LY9, and CD48), and reproduction (AKR1C1, AKR1C3, AKR1C4, and TUSC3). Our findings will be significant in understanding the molecular basis underlying phenotypic variation of breed-related traits and improving productivity in Bashan cattle.
Heat stress is described as the cumulative detrimental effect caused by an imbalance between heat production within the body and heat dissipation. When cattle are exposed to heat stress with skin surface temperatures exceeding 35 degrees C, gene networks within and across cells respond to environmental heat loads with both intra and extracellular signals that coordinate cellular and whole-animal metabolism changes to store heat and rapidly increase evaporative heat loss. In this study, we examined evidence from genes known to be associated with heat tolerance (Hsp70, HSF1, HspB8, SOD1, PRLH, ATP1A1, MTOR, and EIF2AK4). This information could serve as valuable resource material for breeding programs aimed at increasing the thermotolerance of cattle.