BackgroundInsects and animals can recognize surrounding environments by detecting thousands of chemical odorants. Olfaction is a complicated process that begins in the olfactory epithelium with the specific binding of volatile odorant molecules to dedicated olfactory receptors (ORs). OR proteins are encoded by the largest gene superfamily in the mammalian genome.ResultsWe report here the whole genome analysis of the olfactory receptor genes of S. scrofa using conserved OR gene specific motifs and known OR protein sequences from diverse species. We identified 1,301 OR related sequences from the S. scrofa genome assembly, Sscrofa10.2, including 1,113 functional OR genes and 188 pseudogenes. OR genes were located in 46 different regions on 16 pig chromosomes. We classified the ORs into 17 families, three Class I and 14 Class II families, and further grouped them into 349 subfamilies. We also identified inter- and intra-chromosomal duplications of OR genes residing on 11 chromosomes. A significant number of pig OR genes (n = 212) showed less than 60% amino acid sequence similarity to known OR genes of other species.ConclusionAs the genome assembly Sscrofa10.2 covers 99.9% of the pig genome, our analysis represents an almost complete OR gene repertoire from an individual pig genome. We show that S. scrofa has one of the largest OR repertoires, suggesting an expansion of OR genes in the swine genome. A significant number of unique OR genes in the pig genome may suggest the presence of swine specific olfactory stimulation.

The human P-glycoprotein (P-gp) efflux pump is of great interest for medicinal chemists because of its important role in multidrug resistance (MDR). Because of the high polyspecificity as well as the unavailability of high-resolution X-ray crystal structures of this transmembrane protein, ligand-based, and structure-based approaches which were machine learning, homology modeling, and molecular docking were combined for this study. In ligand-based approach, individual two-dimensional quantitative structure-activity relationship models were developed using different machine learning algorithms and subsequently combined into the Ensemble model which showed good performance on both the diverse training set and the validation sets. The applicability domain and the prediction quality of the developed models were also judged using the state-of-the-art methods and tools. In our structure-based approach, the P-gp structure and its binding region were predicted for a docking study to determine possible interactions between the ligands and the receptor. Based on these in silico tools, hit compounds for reversing MDR were discovered from the in-house and DrugBank databases through virtual screening using prediction models and molecular docking in an attempt to restore cancer cell sensitivity to cytotoxic drugs.

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Swine leukocyte antigens play indispensable roles in immune responses by recognizing a large numberof foreign antigens and thus, their genetic diversity plays a critical role in their functions. in this study, we developed a new high-resolution typing method for pig SLA-1 and successfully typed 307 individuals from diverse genetic backgrounds including 11 pure breeds, 1 cross bred, and 12 cell lines. We identified a total of 52 alleles including 18 novel alleles and 9 SLA-1 duplication haplotypes, including 4 new haplotypes. We observed significant differences in the distribution of SLA-1 alleles among the different pig breeds, including the breed specific alleles. SLA-1 duplication was observed in 33% of the chromosomes and was especially high in the biomedical model breeds such as SNU (100%) and NIH (76%) miniature pigs. Our analysis showed that SLA-1 duplication is associated with the increased level of SLA-1 mRnA expression in porcine cells compared to that of the single copy haplotype. therefore, we provide here the results of the most extensive genetic analysis on pig SLA-1. open Scientific RepoRtS | (2020) 10:743 | https://doi.org/10.1038/s41598-020-57712-5www.nature.com/scientificreports www.nature.com/scientificreports/ SLA-1, SLA-2, and SLA-3 are constitutively expressed classical MHC class I genes, but their expression may vary depending on the genetic differences. For example, SLA-1 is duplicated in the haplotypes Hp-2.0, Hp-8.0, Hp-11.0, Hp-12.0, Hp-19.0, Hp-20.0, and Hp-27.0 14,24-26 . In addition, SLA-1, 3, and 6 were not expressed in the haplotypes Hp-3.0, Hp-2.0, and Hp-5.0, respectively 24 . Recently, a method was reported to estimate the copy number of SLA-1 and to facilitate our understanding on the functional aspect of SLA-1 duplication 27 . The frequency of SLA-1 duplication could be abundant, but the detailed functional analysis is not been available.Therefore, we developed a genomic DNA based high resolution SLA-1 typing method with high accuracy regardless of CNVs and present the extensive analysis results of SLA-1 diversity including new alleles and haplotypes, and allelic distribution among different breeds. We also analyzed the level of SLA-1 expression in pig cells according to their copy numbers which could affect MHC class I-specific immune responses. The information presented in this study should contribute to improving our understanding on the genetic polymorphisms of SLA-1 in diverse pig breeds. ResultsDetermination of the SLA-1 specific region. To develop a genomic DNA-based typing method of SLA-1, the determination of conserved locus specific region to design SLA-1 specific primers is required. We previously reported the locus specific nucleotide sequence variations at the downstream promoter region from six classical SLA class I-related genes including . Here, we extended the results by incorporating genomic sequences from additional cloning and sequence analysis. As a result, we identified a SLA-1 specific motif between the TATA box and the CAP site in the 5ʹ UTR and designe...