Impact of graded levels of coated calcium butyrate on growth performance and serological indices during pre-weaning stage in Holstein calves.

The study aimed to analyze the impact of calcium butyrate supplementation in calf starter on growth performance indices associated with early rumen development to decrease the volume of milk or milk replacer feeding and enhance early starter intake in Holstein calves. For this purpose, twelve Holstein calves were randomly assigned into three treatments (n = 4/treatment); a control without coated calcium butyrate, T1, and T2 treatments supplemented with coated calcium butyrate 3 g and 6 g per day/head, respectively. Body weight was measured at days 7, 14, 21, 28, 35, 42, 49, and 56 of the trial, and the average daily weight gain and feed conversion ratio were determined. Blood samples were collected at 14, 28, 42, and 56 days of trial for serological parameters. Gut morphometry was performed at the end of trial at slaughtering by collecting duodenal samples. Furthermore, the meat was also evaluated for its quality parameters including pH and tenderness after slaughtering. The results indicated that the feed intake, average daily weight gain, feed conversion ratio, and gut morphometric parameters involving villus height and crypts depth of calves were improved in coated calcium butyrate-supplemented groups. Furthermore, the supplementation of calf starter with coated calcium butyrate significantly enhanced serum concentrations of glucose and total protein. Besides, Beta hydroxy butyrate (BHBA) levels of blood were also found to be elevated in both treatment groups. However, it was revealed that coated calcium butyrate supplementation had no significant effect on meat quality parameters. In conclusion, the supplementation of calf starter with coated calcium butyrate could improve calf performance.

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.

Molecular Evolution of the Activating Transcription Factors Shapes the Adaptive Cellular Responses to Oxidative Stress.

Reactive oxygen species (ROS) play an essential part in physiology of individual cell. ROS can cause damage to various biomolecules, including DNA. The systems that have developed to harness the impacts of ROS are antique evolutionary adaptations that are intricately linked to almost every aspect of cellular function. This research reveals the idea that during evolution, rather than being largely conserved, the molecular pathways reacting to oxidative stress have intrinsic flexibility. The coding sequences of the ATF2, ATF3, ATF4, and ATF6 genes were aligned to examine selection pressure on the genes, which were shown to be very highly conserved among vertebrate species. A total of 33 branches were explicitly evaluated for their capacity to diversify selection. After accounting for multiple testing, significance was determined using the likelihood ratio test with a threshold of p ≤ 0.05. Positive selection signs in these genes were detected across vertebrate lineages. In the selected test branches of our phylogeny, the synonymous rate variation revealed evidence (LRT, p value = 0.011 ≤ 0.05) of gene-wide episodic diversifying selection. As a result, there is evidence that diversifying selection occurred at least once on at least one test branch. These findings indicate that the activities of ROS-responsive systems are also theoretically flexible and may be altered by environmental selection pressure. By determining where the genes encoding these processes are "targeted" during evolution, we may better understand the mechanism of adaptation to oxidative stress during evolution.

Computational Insights into the Structural and Functional Impacts of nsSNPs of Bone Morphogenetic Proteins.

BMPs (bone morphogenetic proteins) are multipurpose (transforming growth factor)TGF-superfamily released cytokines. These glycoproteins, acting as disulfide-linked homo- or heterodimers, are highly potent regulators of bone and cartilage production and repair, cell proliferation throughout embryonic development, and bone homeostasis in the adults. Due to the fact that genetic variation might influence structural functions, this study is aimed to determine the pathogenic effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in BMP genes. The implications of these variations, investigated using computational analysis and molecular models of the mature TGF-ß domain, revealed the impact of modifications on the function of BMP protein. The three-dimensional (3D) structure analysis was performed on the nsSNP Y316S, V386G, E387G, C389G, and C391G nsSNP in the TGF-ß domain of chicken BMP2 and H344P, S347P, V357A nsSNP in the TGF-ß domain of chicken BMP4 protein that was anticipated to be harmful and of high risk. The ability of the proteins to perform variety of tasks interact with other molecules depends on their tertiary structural composition. The current analysis revealed the four most damaging variants (Y316S, V386G, E387G, C389G, and C391G), highly conserved and functional and are located in the TGF-beta domain of BMP2 and BMP4. The amino acid substitutions E387G, C389G, and C391G are discovered in the binding region. It was observed that the mutations in the TGF-beta domain caused significant changes in its structural organization including the substrate binding sites. Current findings will assist future research focused on the role of these variants in BMP function loss and their role in skeletal disorders, and this will possibly help to develop practical strategies for treating bone-related conditions.

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.

Detecting the Population Structure and Scanning for Signatures of Selection in Horses (Equus caballus) From Whole-Genome Sequencing Data.

Animal domestication gives rise to gradual changes at the genomic level through selection in populations. Selective sweeps have been traced in the genomes of many animal species, including humans, cattle, and dogs. However, little is known regarding positional candidate genes and genomic regions that exhibit signatures of selection in domestic horses. In addition, an understanding of the genetic processes underlying horse domestication, especially the origin of Chinese native populations, is still lacking. In our study, we generated whole genome sequences from 4 Chinese native horses and combined them with 48 publicly available full genome sequences, from which 15 341 213 high-quality unique single-nucleotide polymorphism variants were identified. Kazakh and Lichuan horses are 2 typical Asian native breeds that were formed in Kazakh or Northwest China and South China, respectively. We detected 1390 loss-of-function (LoF) variants in protein-coding genes, and gene ontology (GO) enrichment analysis revealed that some LoF-affected genes were overrepresented in GO terms related to the immune response. Bayesian clustering, distance analysis, and principal component analysis demonstrated that the population structure of these breeds largely reflected weak geographic patterns. Kazakh and Lichuan horses were assigned to the same lineage with other Asian native breeds, in agreement with previous studies on the genetic origin of Chinese domestic horses. We applied the composite likelihood ratio method to scan for genomic regions showing signals of recent selection in the horse genome. A total of 1052 genomic windows of 10 kB, corresponding to 933 distinct core regions, significantly exceeded neutral simulations. The GO enrichment analysis revealed that the genes under selective sweeps were overrepresented with GO terms, including "negative regulation of canonical Wnt signaling pathway," "muscle contraction," and "axon guidance." Frequent exercise training in domestic horses may have resulted in changes in the expression of genes related to metabolism, muscle structure, and the nervous system.

Positive selection drives the evolution of endocrine regulatory bone morphogenetic protein system in mammals.

The rapid evolution of reproductive proteins might be driven by positive Darwinian selection. The bone morphogenetic protein family is the largest within the transforming growth factor (TGF) superfamily. A little have been known about the molecular evolution of bone morphogenetic proteins exhibiting potential role in mammalian reproduction. In this study we investigated mammalian bone morphogenetic proteins using maximum likelihood approaches of codon substitutions to identify positive Darwinian selection in various species. The proportion of positively selected sites was tested by different likelihood models for individual codon, and M8 were found to be the best model. The percentage of positively elected sites under M8 are 2.20% with ω = 1.089 for BMP2, 1.6% with ω = 1.61 for BMP 4 0.53% for BMP15 with ω = 1.56 and 0.78% for GDF9 with ω = 1.93. The percentage of estimated selection sites under M8 is strong statistical confirmation that divergence of bone morphogenetic proteins is driven by Darwinian selection. For the proteins, model M8 was found significant for all proteins with ω > 1. To further test positive selection on particular amino acids, the evolutionary conservation of amino acid were measured based on phylogenetic linkage among sequences. For exploring the impact of these somatic substitution mutations in the selection region on human cancer, we identified one pathogenic mutation in human BMP4 and one in BMP15, possibly causing prostate cancer and six neutral mutations in BMPs. The comprehensive map of selection results allows the researchers to perform systematic approaches to detect the evolutionary footprints of selection on specific gene in specific species.

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.

Positive selection of IL-33 in adaptive immunity of domestic Chinese goats.

The identification of the candidate genes that play key role in phenotypic variation in livestock populations can provide new information about evolution and positive selection. IL-33 (71954) (Interleukin) gene is associated with the increased nematode resistance in small ruminants; however, the role of IL-33 for the genetic control of different diseases in Chinese goat breeds is poorly described in scientific literature. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single-nucleotide polymorphism in IL-33 gene. Fixation Index (FST)-based method was used for the outlier loci determination and found that IL-33 was present in outlier area with the provisional combined allocation of mean heterozygosity and FST. Positively selected IL-33 gene was significantly, that is, p(Simul FST < sample FST = 0.98*) present in corresponding positive selection area. Hence, our study provided novel information about the nucleotide variations in IL-33 gene and found to be nonsynonymous which may helpful for the genetic control of diseases by enhancing the immune system in local Chinese goat breeds as well as in other analyzed vertebrate species.

Genetic signature of strong recent positive selection at interleukin-32 gene in goat.

OBJECTIVE: Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL)-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. METHODS: By using fixation index (FST ) based method, IL-32 (9375) gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and FST . Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8) in Codeml program of phylogenetic analysis by maximum liklihood. RESULTS: IL-32 is detected under positive selection using the FST simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%), bison (91.97%), camel (58.39%), cat (56.59%), buffalo (56.50%), human (56.13%), dog (50.97%), horse (54.04%), and rabbit (53.41%) respectively. CONCLUSION: This study provides evidence for IL-32 gene as under significant positive selection in goat.