ABSTRACT
Gene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier "significant" genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution.
Subject(s)
Primates/genetics , Selection, Genetic/genetics , Animals , Biological Evolution , DNA, Ancient/analysis , Evolution, Molecular , Genome, Human/genetics , Humans , Likelihood Functions , Models, Genetic , Phylogeny , Sequence Alignment , Sequence Analysis, DNA/methodsABSTRACT
Latrophilin 1 (presynaptic receptor) binds α-latrotoxin from black widow spider venom and regulates neurotransmitter release from nerve endings. The study of the mechanism of action of this receptor is impeded by the existence of closely related latrophilins 2 and 3. A profile of differences detecting the most differing and identical sites in several proteins was developed in order to obtain highly specific antibodies for differentiation between isoforms of related proteins. In addition, we used an algorithm for prediction of immunogenic sites of the protein, based on the basic vector method. The peptides selected using this algorithm were used for immunization of animals. The resultant sera exhibited the estimated specificity and high affinity for the corresponding receptor forms.
Subject(s)
Algorithms , Epitopes/chemistry , Receptors, Peptide/chemistry , Amino Acid Sequence , Animals , Antibodies/immunology , Epitopes/immunology , Molecular Sequence Data , Protein Isoforms/chemistry , Protein Isoforms/immunology , Rats , Receptors, Peptide/immunologyABSTRACT
The method of mid-infrared molecular spectroscopy allows precise measuring of the concentrations of a large number of biological molecules in a minimal sample volume. Method of projections on latent structures was used for plotting the calibration models. On the basis on mid-infrared spectral data we obtained calibration models for calculation of serum content of various substances: albumin, cholesterol, glucose, total protein, urea, 70 Da heat shock protein, and malonic dialdehyde.
