Accumulation pattern of amino acid substitutions in protein evolution

Summary A simple method for the evolutionary analysis of amino acid sequence data is presented and used to examine whether the number of variable sites (NVS) of a protein is constant during its evolution. The NVSs for hemoglobin and for mitochondrial cytochrome c are each found to be almost constant, and the ratio between the NVSs is close to the ratio between the unit evolutionary periods. This indicates that the substitution rate per variable site is almost uniform for these proteins, as the neutral theory claims. An advantage of the present analysis is that it can be done without knowledge of paleontological divergence times and can be extended to bacterial proteins such as bacterial c-type cytochromes. It is suggested that the NVS of cytochrome c has been almost constant even over the long period (ca. 3.0 billion years) of bacterial evolution but that at least two different substitution rates are necessary to describe the accumulated changes in the sequence. This two clock interpretation is consistent with fossil evidence for the appearance times of photosynthetic bacteria and eukaryotes.     

Isolation of the putative structural gene for the lysine-arginine-cleaving endopeptidase required for processing of yeast prepro-alpha-factor

S. cerevisiae kex2 mutants are defective for the production of two biologically active secreted peptides: killer toxin and the mating pheromone, alpha-factor. Both molecules are excised from larger precursor polypeptides. In normal cells, the alpha-factor precursor is core-glycosylated and proteolytically processed intracellularly. In kex2 mutants, however, prepro-alpha-factor is not proteolytically cleaved and is secreted in a highly glycosylated form. All kex2 mutants examined (three independent alleles) lack a Zn++-sensitive membrane-associated endopeptidase with specificity for cleaving on the carboxyl side of a pair of basic residues. Absence of this activity cosegregates with the other phenotypes of a kex2 lesion in genetic crosses. The normal KEX2 gene was isolated by complementation of three of the phenotypes conferred by the kex2-1 mutation. The cloned DNA, either on a multicopy plasmid or integrated into the genome, restores both enzymatic activity in vitro and the normal pattern of proteolytic processing and glycosylation of prepro-alpha-factor in vivo. Gene dosage effects suggest that KEX2 is the structural gene for the endopeptidase.     

Characteristic base sequence patterns of promoter and terminator sites in phi X174 and fd phage DNAs

An overall theory for the evolution of complexity in passerine broadcast song is advanced based on the proposition that new birds should attempt to match the songs of residents. We assume that social systems result from competition between individuals for resources. Individuals which by aggressive interaction have attained some priority of access to a resource (territory, food, or mate) should advertise this. New birds singing in an area will reveal their non-residential status by their song and hence will announce an assymmetry in competition that favours the residents because of their prior knowledge. Thus new birds should learn to match in order to reduce this asymmetry. Counter-selection on residents to reduce the incidence of matching should favour the evolution of song complexity. The degree of complexity should vary directly with the degree of competition. Predictions from these assumptions are advanced.     

The group II chaperonin TRiC protects proteolytic intermediates from degradation in the MHC class I antigen processing pathway

MHC class I molecules present precisely cleaved peptides of intracellular proteins on the cell surface. For most antigenic precursors, presentation requires transport of peptide fragments into the ER, but the nature of the cytoplasmic peptides and their chaperones is obscure. By tracking proteolytic intermediates in living cells, we show that intracellular proteolysis yields a mixture of antigenic peptides containing only N-terminal flanking residues for ER transport. Some of these peptides were bound to the group II chaperonin TRiC and were protected from degradation. Destabilization of TRiC by RNA interference inhibited the expression of peptide-loaded MHC I molecules on the cell surface. Thus, the TRiC chaperonin serves a function in protecting proteolytic intermediates in the MHC I antigen processing pathway.     

Gene arrangements characteristic of the phylum Actinobacteria

The availability of genomic sequence data allows new challenges to various biological problems. One of such attempts is the extraction of phylogenetic information from gene order data of genomes. Phylogenetic inferences are most commonly carried out on the basis of 16S rRNA trees, which sometimes produce unresolved or unreliable branching orders. One example for such a low resolution is recognized in the branching pattern among the phylum Actinobacteria. Here, gene arrangements characteristic of the Actinobacteria were identified, based on which Symbiobacterium thermophilum is phylogenetically placed outside that phylum, this being in contrast to 16S rRNA trees and to the current taxonomy in GenBank. Three transposition suggestive arrangements were found which support a notion that Rubrobacter xylanophilus is the earliest diverging species among the completely sequenced Actinobacteria. The gene arrangements identified here serve as a complement to previously reported indels and proteins characteristic of this phylum.     

Loureirin C and Xanthoceraside Attenuate Depression-Like Behaviors and Expression of Interleukin-17 in the Prefrontal Cortex Induced by Chronic Unpredictable Mild Stress in Mice

Neurochemical Research - Major depressive disorder (MDD) is the most prevalent and serious psychiatric disease involving inflammation. Loureirin C and Xanthoceraside are extracts of dragon’s...     

Dietary folic Acid promotes survival of foxp3+ regulatory T cells in the colon

Dietary compounds as well as commensal microbiota contribute to the generation of a unique gut environment. In this study, we report that dietary folic acid (FA) is required for the maintenance of Foxp3(+) regulatory T cells (Tregs) in the colon. Deficiency of FA in the diet resulted in marked reduction of Foxp3(+) Tregs selectively in the colon. Blockade of folate receptor 4 and treatment with methotrexate, which inhibits folate metabolic pathways, decreased colonic Foxp3(+) Tregs. Compared with splenic Tregs, colonic Tregs were more activated to proliferate vigorously and were highly sensitive to apoptosis. In colonic Tregs derived from mice fed with a FA-deficient diet, expression of anti-apoptotic molecules Bcl-2 and Bcl-xL was severely decreased. A general reduction of peripheral Tregs was induced by a neutralizing Ab against IL-2, but a further decrease by additional FA deficiency was observed exclusively in the colon. Mice fed with an FA-deficient diet exhibited higher susceptibility to intestinal inflammation. These findings reveal the previously unappreciated role of dietary FA in promotion of survival of Foxp3(+) Tregs that are in a highly activated state in the colon.