Genomic and Computational Analysis of Novel SNPs in TNP1 Gene Promoter Region of Bos indicus Breeding Bulls.

Transition nuclear proteins (TNPs), the principal proteins identified in the condensing spermatids chromatin, have been found to play a key role in histone displacement and chromatin condensation during mammalian spermatogenesis. One such gene belonging to the TNP family called TNP1 gene is abundantly expressed in the regulation of spermatogenesis, and its sequence is remarkably well conserved among mammals. Genomic analysis, by sequencing and computational approach, was used to identify the novel polymorphisms and to evaluate the molecular regulation of TNP1 gene expression in Sahiwal cattle breeding bulls. DNA samples were sequenced to identify novel single nucleotide polymorphisms (SNPs) in the TNP1 gene. Modern computational tools were used to predict putative transcription factor binding in the TNP1 promoter and CpG islands in the TNP1 promoter region. In the TNP1 gene, four SNPs, three TATA boxes, and one CAAT box were identified. One CAAT box was discovered at 89 bp upstream of start site ATG. The computational analyses indicated that the polymorphisms inside the promoter sequence results in an added HNF-1 transcription factor binding site. In contrast, the other variations may remove the naturally occurring SRF transcription factor binding site. The CpG islands in the TNP1 promoter region were predicted to be absent by the MethPrimer program before and after SNP site mutations. These findings pave the way for more research into the TNP1 gene's promoter activity and the links between these SNPs and reproductive attributes in the Sahiwal breeding bulls.

Effects of Ferula asafetida, closantel, albendazole, oxfendazole, and ivermectin against Haemonchus contortus in goats and sheep.

BACKGROUND: Haemonchosis is a fatal disease of small ruminants caused by the parasite Haemonchus contortus (H. contortus). The most common drugs used in the treatment of H. contortus include albendazole, oxfendazole, and ivermectin. However, as previously reported in the treatment of haemonchosis, these medicines have acquired drug resistance problems over time. Interestingly, natural plant compounds have demonstrated promising effects in the treatment of H. contortus. Therefore, the current study evaluated the effects of plant extract, Ferula asafetida, against common drugs such as albendazole, oxfendazole, ivermectin, and closantel for the treatment of haemonchosis in small ruminants. METHODOLOGY: The current study was conducted on different small ruminant farms in Kasur District, Punjab, Pakistan. The positive animals (n = 720) after coprological examination were selected in this study and divided into two major groups (n = 360 goats and n = 360 sheep). Further, animals were divided into five treatment groups (A-E) and one control group with no treatment (F). Albendazole, oxfendazole, ivermectin, closantel, and Ferula asafetida were administered orally to groups A-E, respectively. The eggs per gram feces (EPG) were determined through the McMaster technique on days 0, 7th, and 14th of treatment. RESULTS: The results showed a significantly higher efficacy of closantel and Ferula asafetida against H. contortus in both goats (100% and 70%; p < 0.05) and sheep (99% and 87%; p < 0.05), respectively. No correlation was observed between EPG reduction with age and gender in both goats and sheep. CONCLUSION: Allopathic drug closantel and herbal drug, Ferula asafetida, have been proved an effective dewormer against H. contortus in small ruminants.

Behind the Scene: Surprises and Snags of Pseudogenes.

The junk DNA "pseudogenes," known as genomic fossils, are characterized by their ubiquitousness and abundance within the genomic structure. These genomics sets are recognized by the potential activity of meta-regulating the parent genes; these are transcribed into interfering RNA, consequently acting on miRNA concentration, thereby shedding light on the crosstalk of the pseudogenes' miRNA, siRNA, lncRNA/tumor therapy co-relationship. Moreover, an upcoming visualization regarding pseudogenes is under investigation, which describes the potentiality of pseudogenes as a fundamental component of cancerous evolutionary processing tools. Accordingly, here is a systematic review covering pseudobirth, pseudosignatures, and functional properties of pseudogenes, concluding that these pseudogenes are hypothetically predictive tumor therapies.

Comparative analysis of the mitochondrial proteins reveals complex structural and functional relationships in Fasciola species.

Mitochondria is a cellular source of energy, appears to play an essential role in dealing with cellular stress induced by environmental stimuli. The genetic diversity of mitochondrial genes involved in oxidative phosphorylation affecting the production of cellular energy and regional adaptation to various ecological (climatic) pressures affecting amino acid sequences (variants of protein). However, little is known about the combined effect of protein changes on cell-level metabolic alterations in simultaneous exposure to various environmental conditions, including mitochondrial dysfunction and oxidative stress induction. The present study was designed to address this issue by analyzing the mitochondrial proteins in Fasciola species including Cytochrome oxidase (COX1, COX2, COX3, and CYTB) and NADH dehydrogenase (ND1, ND2, ND3, ND4, ND5, and ND6). Mitochondrial proteins were used for detailed computational investigation, using available standard bioinformatics tools to exploit structural and functional relationships. These proteins in Fasciola hepatica, Fasciola gigentica, and Fasciola jacksoni were functionally annotated using public databases. The results showed that the protein of COX1 of F. hepatica, F. gigantica, and F. jacksoni consist of 510, 513, and 517 amino acids, respectively. The alignment of proteins showed that these proteins are conserved in the same regions at ten positions in COX and CYTB proteins while at twelve locations in NADH. Three-dimensional structure of COX, CYTB, and NADH proteins were compared and showed differences in additional conserved and binding sites in COX and CYTB proteins as compared to NADH in three species of Fasciola. These results based on the amino acid diversity pattern were used to identify sites in the enzyme and the variations in mitochondrial proteins among Fasciola species. Our study provides valuable information for future experimental studies, including identification of therapeutic, diagnostic, and immunoprophylactic interests with novel mitochondrial proteins.

Autonomous Vision-Based Primary Distribution Systems Porcelain Insulators Inspection Using UAVs.

The early detection of damaged (partially broken) outdoor insulators in primary distribution systems is of paramount importance for continuous electricity supply and public safety. Unmanned aerial vehicles (UAVs) present a safer, autonomous, and efficient way to examine the power system components without closing the power distribution system. In this work, a novel dataset is designed by capturing real images using UAVs and manually generated images collected to overcome the data insufficiency problem. A deep Laplacian pyramid-based super-resolution network is implemented to reconstruct high-resolution training images. To improve the visibility of low-light images, a low-light image enhancement technique is used for the robust exposure correction of the training images. A different fine-tuning strategy is implemented for fine-tuning the object detection model to increase detection accuracy for the specific faulty insulators. Several flight path strategies are proposed to overcome the shuttering effect of insulators, along with providing a less complex and time- and energy-efficient approach for capturing a video stream of the power system components. The performance of different object detection models is presented for selecting the most suitable one for fine-tuning on the specific faulty insulator dataset. For the detection of damaged insulators, our proposed method achieved an F1-score of 0.81 and 0.77 on two different datasets and presents a simple and more efficient flight strategy. Our approach is based on real aerial inspection of in-service porcelain insulators by extensive evaluation of several video sequences showing robust fault recognition and diagnostic capabilities. Our approach is demonstrated on data acquired by a drone in Swat, Pakistan.

Adaptive evolution of peptidoglycan recognition protein family regulates the innate signaling against microbial pathogens in vertebrates.

The innate immune system is the first line of defense in vertebrates against microbial pathogens. This defense system depends on the peptidoglycan pathogen recognition of receptors (PGRPs) existing in both invertebrates and vertebrates. Although some studies revealed the structural and functional differences between them, however, the evolutionary history and the selection pressures on these genes during adaptive evolution are poorly understood. In this study, we examined four (PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4) genes of 127 vertebrates' species, conserved across vertebrates to evaluate positive selection pressure drives by adaptive evolution. The codons under positive selection were recognized through likelihood tests by comparing different models based on ω ratios in these genes across the vertebrate species. The positive selection test used two sets of models M1a vs. M2a and M7 vs. M8. The results showed that the test of these genes in M1a vs. M2a was not significant with the likelihood value 2ΔlnL = 0, while the likelihood ratios (2ΔlnL) were 2ΔlnL = 12.386, 2ΔlnL = 4.9283, 2ΔlnL = 24.031, and 2ΔlnL = 103.39 for PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4 in M7 vs. M8, respectively. Our study identified the evidence of robust positive selection for these four genes across the vertebrates. These protuberant changes in PGRPs evolution of vertebrates reveal their role in innate immunity. Our study provides an insight based on PGRP genes to understand the evolution of host and pathogens interaction that leads to the progress of the novel conducts for immune diseases that include proteins linked to the recognition of pathogens.

Adaptation to host-specific bacterial pathogens drive rapid evolution of novel PhoP/PhoQ regulation pathway modulating the virulence.

The presence of the PhoP-PhoQ system is usually different in various bacterial groups, suggesting that PhoP can control the expression of different genes in species. However, little is known about the evolution of the PhoP-PhoQ system among bacterial pathogens. Here, we study the evolution of PhoP and PhoQ regulation in 15 species of Enterobacteriaceae family. We have determined that the regulatory objectives adopted by PhoP and PhoQ are mainly different, due to the result of horizontal gene transfer events and even the change in the genetic content between closely related species. We have compared many possibilities tests (M1 vs. M2 and M7 with M8) to determine the positive selection. Estimating parameters at M1 and M2, with positive selection in M2 of the two proteins. The proportions of positive selection sites significant with ω = 4.53076 for PhoP and ω = 4.21041 PhQ. M8 was significant for PhoP and PhQ proteins. To further confirm the positive selection results, we used the Selecton server to confer positive selection on individual sites using the Mechanistic-Empirical Combination model, and we noticed that several sites had been identified under selection pressure during the evolution. There was a strong indication for the positive selection in bacterial genes of PhoP and PhoQ showed the results. By the use of REL and IFEL, the positive selection for PhoP was detected 14 and 11 sites respectively at different codon positions. The positively selected sites of amino acids such as Arginine, Alanine, Lysine, and Leucine are more important for the production of signals. Our results suggest that the positive selection of PhoP-PhoQ genes in host adaptation during evolution raises an intriguing possibility causes subtle variations in actions of PhoP-PhoQ and also increases the opportunities that cause modification in protein structure for the evolution of increasing pathogenicity in bacterial pathogens.

Full-length transcriptome sequencing and comparative transcriptomic analysis to uncover genes involved in early gametogenesis in the gonads of Amur sturgeon (Acipenser schrenckii).

BACKGROUND: Sturgeons (Acipenseriformes) are polyploid chondrostean fish that constitute an important model species for studying development and evolution in vertebrates. To better understand the mechanisms of reproduction regulation in sturgeon, this study combined PacBio isoform sequencing (Iso-Seq) with Illumina short-read RNA-seq methods to discover full-length genes involved in early gametogenesis of the Amur sturgeon, Acipenser schrenckii. RESULTS: A total of 50.04 G subread bases were generated from two SMRT cells, and herein 164,618 nonredundant full-length transcripts (unigenes) were produced with an average length of 2782 bp from gonad tissues (three testes and four ovaries) from seven 3-year-old A. schrenckii individuals. The number of ovary-specific expressed unigenes was greater than those of testis (19,716 vs. 3028), and completely different KEGG pathways were significantly enriched between the ovary-biased and testis-biased DEUs. Importantly, 60 early gametogenesis-related genes (involving 755 unigenes) were successfully identified, and exactly 50% (30/60) genes of those showed significantly differential expression in testes and ovaries. Among these, the Amh and Gsdf with testis-biased expression, and the Foxl2 and Cyp19a with ovary-biased expression strongly suggested the important regulatory roles in spermatogenesis and oogenesis of A. schrenckii, respectively. We also found the four novel Sox9 transcript variants, which increase the numbers of regulatory genes and imply function complexity in early gametogenesis. Finally, a total of 236,672 AS events (involving 36,522 unigenes) were detected, and 10,556 putative long noncoding RNAs (lncRNAs) and 4339 predicted transcript factors (TFs) were also respectively identified, which were all significantly associated with the early gametogenesis of A. schrenckii. CONCLUSIONS: Overall, our results provide new genetic resources of full-length transcription data and information as a genomic-level reference for sturgeon. Crucially, we explored the comprehensive genetic characteristics that differ between the testes and ovaries of A. schrenckii in the early gametogenesis stage, which could provide candidate genes and theoretical basis for further the mechanisms of reproduction regulation of sturgeon.

Bioinformatics Approaches to Explore the Phylogeny and Role of BRCA1 in Breast Cancer.

BRCA1 and BRCA2 are the two major vulnerability genes involved in hereditary breast cancer. BRCA1 gene programs for a tumor suppressor protein that helps in repairing DNA. The purpose of this study was to reveal the position and nature of amino acid residues involved in breast cancer, and it provides a complete characterization of BRCA1 and its evolutionary relationship with 34 selected organisms. The sequences were retrieved from NCBI, and after analyzing them in BLAST, a complete annotation of both types of genes from a human was done; in addition, a phylogenetic analysis was performed from 34 different organisms to study evolutionary relationships of BRCA1. A total of 1080 positions of genes were found in the dataset in which the first 3 were noncoding positions and the remaining were all coding regions. A tree was originated using MEGA that showed strong evolutionary relationships among three orders (Catertiodactyla, carnivore, and primates) of these organisms, which are closely related to each other. All features of wild and mutant proteins were studied by ProtParam. The location and number of alpha helices, beta sheets, coils, strands, and the binding regions, disordered regions were identified using different tools (SOPMA, PHD, and GOR4) and their percentages greatly varied. Our study revealed that the BRCA1 gene involved in cancer development had a weaker selection than those involved in sporadic cancer. Our investigation showed that in mammals, selection acting on human cancer genes drives adaptive variations in behaviors related to organismal fitness, rather than select for biological roles directly linked to cancer.

Role of genome-wide mRNA-seq profiling in understanding the long-term sperm maintenance in the storage tubules of laying hens.

Sperm storage function of the sperm storage tubules (SSTs) is directly correlated with the fertility of laying hens. SSTs are located at the utero-vaginal junction (UVJ) and infundibulum of the hen oviduct. However, little is known about the cellular and molecular mechanisms responsible for long-term sperm maintenance in the lumen of the SSTs. In this study, we profiled transcriptomes to detect the different gene expressions between infundibulum and UVJ using RNA-seq. As a result, we identified a total of 1382 differentially expressed genes (DEGs). GO analysis showed that fat acid metabolism, regulation of cell differentiation, regulation of transport, and immune response were enriched for these DEGs, and many of the pH-regulatory functions genes such as CAIV and SLC4A4 were highly expressed in UVJ, which inferred that SSTs could preserve sperm by regulating physiological functions in UVJ. Our results provide new insight to understand the specific function for SSTs to extend sperm life span in the oviduct of laying hens.

Applications of CRISPR/Cas9 in Reproductive Biology.

Genome editing is unraveling its benefits in wide areas of scientific development and understanding. The advances of genome editing from ZFNs and TALLENs to CRISPRs defines it wide applicability. Reproduction is the fundamental process by which all organisms maintain their generations. CRISPR/Cas9, a new versatile genome editing tool is recently tamed to correct several disease causing genetic mutations spreading its arms to improve reproductive health. It not only edit harmful genetic mutations but is also applied to control the spread of parasitic diseases like malaria by introducing selfish genetic elements, propagated through generations and population via reproduction. These applications made us to review the recent developments of CRISPRs use in reproductive biology.

A Review of CRISPR-Based Genome Editing: Survival, Evolution and Challenges.

Precise nucleic acid editing technologies have facilitated the research of cellular function and the development of novel therapeutics, especially the current programmable nucleases-based editing tools, such as the prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated nucleases (Cas). As CRISPR-based therapies are advancing toward human clinical trials, it is important to understand how natural genetic variation in the human population may affect the results of these trials and even patient safety. The development of "base-editing" technique allows the direct, stable transformation of target DNA base into an alternative in a programmable way, without DNA double strand cleavage or a donor template. Genome-editing techniques hold promises for the treatment of genetic disease at the DNA level by blocking the sequences associated with disease from producing disease-causing proteins. Currently, scientists can select the gene they want to modify, use the Cas9 as a "molecular cutter" to cut it out, and transform it into a more desirable version. In this review, we focus on the recent advances of CRISPR/Cas system by outlining the evolutionary and biotechnological implications of current strategies for improving the specificity and accuracy of these genome-editing technologies.

Peptide vaccine against chikungunya virus: immuno-informatics combined with molecular docking approach.

BACKGROUND: Chikungunya virus (CHIKV), causes massive outbreaks of chikungunya infection in several regions of Asia, Africa and Central/South America. Being positive sense RNA virus, CHIKV replication within the host resulting in its genome mutation and led to difficulties in creation of vaccine, drugs and treatment strategies. Vector control strategy has been a gold standard to combat spreading of CHIKV infection, but to eradicate a species from the face of earth is not an easy task. Therefore, alongside vector control, there is a dire need to prevent the infection through vaccine as well as through antiviral strategies. METHODS: This study was designed to find out conserved B cell and T cell epitopes of CHIKV structural proteins through immuno-informatics and computational approaches, which may play an important role in evoking the immune responses against CHIKV. RESULTS: Several conserved cytotoxic T-lymphocyte epitopes, linear and conformational B cell epitopes were predicted for CHIKV structural polyprotein and their antigenicity was calculated. Among B-cell epitopes "PPFGAGRPGQFGDI" showed a high antigenicity score and it may be highly immunogenic. In case of T cell epitopes, MHC class I peptides 'TAECKDKNL' and MHC class II peptides 'VRYKCNCGG' were found extremely antigenic. CONCLUSION: The study led to the discovery of various epitopes, conserved among various strains belonging to different countries. The potential antigenic epitopes can be successfully utilized in designing novel vaccines for combating and eradication of CHIKV disease.

A review on epidemiology, global prevalence and economical losses of fasciolosis in ruminants.

Fasciolosis is an important plant borne trematode zoonosis in ruminants caused by the Fasciola hepatica and Fasciola gigentica, It is classified as a neglected tropical disease and found in more than 50 countries especially where sheep and cattle are reared. Fasciolosis is a serious animal health problems in many rural and urban areas of world, causing significant financial losses due to decrease in production and viscera condemnation in animals. Accurate diagnosis of fasciolosis is always remained a challenging task for the field practitioners. There is no comprehensive summary on the occurrence and distribution of the infection at international level. Therefore, we intended to provide a complete overview on the prevalence and epidemiology of fasciolosis in farm animals from a global prospective. It includes to map the global distribution of fasciolosis in different areas of the world to identify the endemic regions which may be a source of potential disease outbreak. The financial liability related to fasciolosis on the livestock production has also been addressed. For this purpose, the published data during 2000-2015 (15 years) on fasciolosis was reviewed and collected by electronic literature search of four databases including Google, PubMed, Science Direct, and Web of Science. Data presented are contemplated to enhance our current understanding of the parasite's geographical distribution, host range, and economic losses. Information provided would be useful for the application of more effective control strategies against fasciolosis in different geo-economics regions of the world.

WITHDRAWN: Adaptive selection at agouti gene inferred breed specific selection signature within the indigenous goat populations.

Ahead of Print article withdrawn by publisher.

Evaluation of phytochemicals from Thymus serpyllum as potential drug candidates to manage oxidative stress in transition dairy cows.

Dairy cows undergo immense stress and experience autoimmune reactions during the transition period, majorly due to the generation of ROS in the body. So, pharmacological approaches are needed to manage oxidative stress in the transition cows. Recently, the use of phytochemicals as feed additives in cows' nutrition has gained interest in managing various disease conditions. In the current study, we have evaluated the potential effects of phytochemicals derived from methanolic extract of Thymus serpyllum against oxidative stress and autoimmunity via inhibition of bovine nuclear factor kappa B (NF-κB). The free radical scavenging activity of Thymus serpyllum seed and leaf extracts was 71.8 and 75.6%, respectively at 100 µg/mL concentration. Similarly, both extracts displayed radicals reducing power and inhibition of lipid-peroxidation maximally at 100 µg/mL. A total of 52 bioactive compounds were identified when the plant extract was characterized by the GC-MS analysis, and five (Thymol, Luteolin 7-o-glucuronide, Rosmarinic acid, Apigenin 6,8-di-c-glucoside, Kaempferol) had binding free energy values of -11.6433, -10.002, -8.2615, -7.1714, -6.4870, respectively, in complexes with bovine NF-κB. Through computational analysis, the screened compounds showed good pharmacokinetic parameters, including non-toxicity, non-carcinogenic, high gastrointestinal absorption and thus can serve as potential drug candidates. MD simulation studies predicted the stability of complexes and the complex of Kaempferol was most stable based on RSMD value and MM/GBSA binding energy. The biochemical assays and computational studies indicated that Thymus serpyllum could be used as a promising feed additive in dairy cows to manage oxidative stress during the transition period.Communicated by Ramaswamy H. Sarma.

Genomic insights into Yak (Bos grunniens) adaptations for nutrient assimilation in high-altitudes.

High-altitude environments present formidable challenges for survival and reproduction, with organisms facing limited oxygen availability and scarce nutrient resources. The yak (Bos grunniens), indigenous to the Tibetan Plateau, has notably adapted to these extreme conditions. This study delves into the genomic basis of the yak's adaptation, focusing on the positive selection acting on genes involved in nutrient assimilation pathways. Employing techniques in comparative genomics and molecular evolutionary analyses, we selected genes in the yak that show signs of positive selection associated with nutrient metabolism, absorption, and transport. Our findings reveal specific genetic adaptations related to nutrient metabolism in harsh climatic conditions. Notably, genes involved in energy metabolism, oxygen transport, and thermoregulation exhibited signs of positive selection, suggesting their crucial role in the yak's successful colonization of high-altitude regions. The study also sheds light on the yak's immune system adaptations, emphasizing genes involved in response to various stresses prevalent at elevated altitudes. Insights into the yak's genomic makeup provide valuable information for understanding the broader implications of high-altitude adaptations in mammalian evolution. They may contribute to efforts in enhancing livestock resilience to environmental challenges.

Liver Transcriptome Profiling Identifies Key Genes Related to Lipid Metabolism in Yili Geese.

The Yili goose is the only indigenous goose breed that originates from Anser anser in China, known for its adaptability, strong flying ability, and tender meat with a low body lipid content. The liver plays a crucial role in lipid and glucose metabolism, including the intake, secretion, transportation, and storage of fatty acids (FAs). In this study, RNA-sequencing (RNA-seq) technology was performed to analyze the liver differentially expressed genes of Yili geese and their hybrid geese to investigate differences in liver lipid and glucose metabolism. A total of 452 differentially expressed genes (Q-value < 0.05) were identified. Notably, in KEGG enrichment analysis, four pathways (Q-value < 0.05) were enriched to be associated with lipid and glucose metabolism, including the metabolic pathway, PI3K-Akt signaling pathway, glycolysis/gluconeogenesis, and steroid biosynthesis. This study provides insights into potential candidate genes and metabolic pathways that affect the liver lipid metabolism of Yili goose. These findings provide a better understanding of animal liver lipid deposition and metabolism.

Structural and Phylogenetic Analysis of CXCR4 Protein Reveals New Insights into Its Role in Emerging and Re-Emerging Diseases in Mammals.

Chemokine receptor type 4 (CXCR4) is a G protein-coupled receptor that plays an essential role in immune system function and disease processes. Our study aims to conduct a comparative structural and phylogenetic analysis of the CXCR4 protein to gain insights into its role in emerging and re-emerging diseases that impact the health of mammals. In this study, we analyzed the evolution of CXCR4 genes across a wide range of mammalian species. The phylogenetic study showed species-specific evolutionary patterns. Our analysis revealed novel insights into the evolutionary history of CXCR4, including genetic changes that may have led to functional differences in the protein. This study revealed that the structural homologous human proteins and mammalian CXCR4 shared many characteristics. We also examined the three-dimensional structure of CXCR4 and its interactions with other molecules in the cell. Our findings provide new insights into the genomic landscape of CXCR4 in the context of emerging and re-emerging diseases, which could inform the development of more effective treatments or prevention strategies. Overall, our study sheds light on the vital role of CXCR4 in mammalian health and disease, highlighting its potential as a therapeutic target for various diseases impacting human and animal health. These findings provided insight into the study of human immunological disorders by indicating that Chemokines may have activities identical to or similar to those in humans and several mammalian species.

A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene.

Leptin is a polypeptide hormone produced in the adipose tissue and governs many processes in the body. Recently, polymorphisms in the LEP gene revealed a significant change in body weight regulation, energy balance, food intake, and reproductive hormone secretion. This study considers its crucial role in the regulation of the economically important traits of sheep. Several computational tools, including SIFT, Predict SNP2, SNAP2, and PROVEAN, have been used to screen out the deleterious nsSNPs. Following the screening of 11 nsSNPs in the sheep genome, 5 nsSNPs, T86M (C → T), D98N (G → A), N136T (A → C), R142Q (G → A), and P157Q (C → A), were predicted to have a significant deleterious effect on the LEP protein function, leading to phenotypic difference. The analysis of proteins' stability change due to amino acid substitution using the I-stable, SDM, and DynaMut consistently confirmed that three nsSNPs (T86M (C → T), D98N (G → A), and P157Q (C → A)) increased protein stability. It is suggested that these three nsSNPs may enhance the evolvability of LEP protein, which is vital for the evolutionary adaptation of sheep. Our findings demonstrate that the five nsSNPs reported in this study might be responsible for sheep's structural and functional modifications of LEP protein. This is the first comprehensive report on the sheep LEP gene. It narrow downs the candidate nsSNPs for in vitro experiments to facilitate the development of reliable molecular markers for associated traits.