Evolution-driving genes

Genomic sequences provide evidence for a common origin of life and its evolution via selection of genetic variants created by mutation and recombination. Two classes of genes are known to accelerate mutation and/or recombination rates in bacterial populations: stress-inducible wild-type genes, usually part of the SOS regulon, and genes whose functional loss, or downregulation, increases the rate of genetic variability (mutator and/or hyper-rec mutants).     

Stable genes

Some genes such as those for histones and RNAs are conserved unchanged through much of evolution and have numerous tandem repeat copies in the genome. It is proposed that as yet undetected 'polystrand' enzymes use such multiple copies as a means of conserving their sequence by comparing the copies and eliminating errors.     

Interpreting humanity's genes

Genetic medicine is said to be entering another era. Recent technological developments such as high resolution array techniques and next-generation sequencing have dramatically increased the power of genetic testing. However, the function of the majority of genes remains unknown. The complex interactions underpinning gene expression in humans can be studied only in part by laboratory and animal studies, and will require studies in humans. Consequently, observational studies which systematically record human phenotype data are urgently needed to interpret molecular genetic variation.     

Inflammation and genes

Inflammation is a protective immune response to infection, trauma, or injury; however, only a subset of patients develops inflammation, suggesting other contributing factors involved, such as the environment and genes. Inflammation-associated genes involving those with pro- and anti-inflammatory effect should be properly balanced and regulated; the protein products of these genes ultimately determine the outcome of inflammation. Apart from gene mutations, gene polymorphisms related to some inflammatory markers also appear to correlate with the incidence and/or outcome of serious inflammatory events. Some genes recently recognized to be associated with inflammation are briefly reviewed. Modern genomic approaches, such as DNA micro-arrays and serial analysis of gene expression, allow for determining the extremely complex profile of inflammatory genes.     

Displacement of epsilon-proteobacterial core genes by horizontally transferred homologous genes

The introduction of novel genes by horizontal gene transfer (HGT) is considered an alternative mechanism for genetic adaptation, leading to diversification and speciation. The goal of this study was to determine which genes that are present in all sequenced epsilon-proteobacterial genomes were acquired by HGT. In our approach we used BLAST analysis to reduce the number of genes that subsequently needed to be analysed using more in-depth phylogenetic methods, including neighbour-joining and maximum likelihood. Among the 991 core genes found in all five completed epsilon-proteobacterial genome sequences, we identified 30 genes that were probably acquired by HGT. It is proposed that these genes displaced an ancestral core gene with a similar function. Although it was not possible to identify putative donor taxa for all acquired genes, it was clear that genes were acquired from a wide range of Bacteria, including Spirochaetes, Firmicutes, Actinobacteria, mycoplasmas and several subdivisions of the Proteobacteria. We did not observe HGT from Archaea to the epsilon-Proteobacteria. The majority of acquired genes were operational genes involved in transport, metabolism, signal transduction and energy production and conversion.     

Mapping autoimmunity genes

Rat and mouse models for the major human autoimmune/inflammatory diseases are under intense genetic scrutiny. Genome-wide linkage studies reveal that each model is regulated by multiple genetic loci. Many of these loci colocalize to homologous genomic regions associated with several different autoimmune diseases of mice, rats and humans. Candidate genes are being identified. Polymorphic alleles associated with these chromosomal segments may represent predisposing genetic elements common to a number of human diseases with very different clinical presentations.     

记忆抑制基因

长期记忆贮存分子基础研究最重要的进展之一是揭示了记忆的巩固涉及基因表达的改变。与肿瘤发生和形成的早期研究集中在生长的正向调节基因 (即显性活跃的致癌基因 )相似 ,既往关于长期记忆和突触可塑性分子水平的研究也主要集中于正向调节基因上。近几年提出了关于突触变化启动核内变化导致基因表达过程的多种分子模型 [1 ] ,这些模型受肿瘤发生和发展的信号转导理论启示 ,其中最引人注目的发现之一是揭示长期持续的突触可塑性变化不但需要有利于记忆贮存的正向调节机制的激活 ,同时也需要清除阻止记忆贮存的抑制性因素。正如正常状况下肿…     

Rhabdovirus accessory genes

The Rhabdoviridae is one of the most ecologically diverse families of RNA viruses with members infecting a wide range of organisms including placental mammals, marsupials, birds, reptiles, fish, insects and plants. The availability of complete nucleotide sequences for an increasing number of rhabdoviruses has revealed that their ecological diversity is reflected in the diversity and complexity of their genomes. The five canonical rhabdovirus structural protein genes (N, P, M, G and L) that are shared by all rhabdoviruses are overprinted, overlapped and interspersed with a multitude of novel and diverse accessory genes. Although not essential for replication in cell culture, several of these genes have been shown to have roles associated with pathogenesis and apoptosis in animals, and cell-to-cell movement in plants. Others appear to be secreted or have the characteristics of membrane-anchored glycoproteins or viroporins. However, most encode proteins of unknown function that are unrelated to any other known proteins. Understanding the roles of these accessory genes and the strategies by which rhabdoviruses use them to engage, divert and re-direct cellular processes will not only present opportunities to develop new anti-viral therapies but may also reveal aspects of cellar function that have broader significance in biology, agriculture and medicine.     

Blood group genes

Blood group antigens are surface markers on the red blood cell membrane. Biochemical analysis of blood group antigens has shown that these antigens divide into two types of proteins and carbohydrates attached to lipids or proteins. Protein determinants are directly coded on blood group genes, while carbohydrate determinants are controlled through the expression of glycosyltransferase enzymes. For the past ten years, considerable information has been gained from molecular studies of many blood group systems, thereby clarifying several aspects of these genes, genetic backgrounds of variants, and molecular evolution. Additionally, it has become possible to genotype blood groups and to genetically engineer the expression of protein antigens and the activity and specificity of enzymes. ABO system on the carbohydrate and Rh system on the protein are the most important systems in transfusion medicine. In this paper, we will review recent progress in the field of blood grouping; mainly ABO and Rh.     

Identification of novel virulence-associated genes via genome analysis of hypothetical genes

The sequencing of bacterial genomes has opened new perspectives for identification of targets for treatment of infectious diseases. We have identified a set of novel virulence-associated genes (vag genes) by comparing the genome sequences of six human pathogens that are known to cause persistent or chronic infections in humans: Yersinia pestis, Neisseria gonorrhoeae, Helicobacter pylori, Borrelia burgdorferi, Streptococcus pneumoniae, and Treponema pallidum. This comparison was limited to genes annotated as hypothetical in the T. pallidum genome project. Seventeen genes with unknown functions were found to be conserved among these pathogens. Insertional inactivation of 14 of these genes generated nine mutants that were attenuated for virulence in a mouse infection model. Out of these nine genes, five were found to be specifically associated with virulence in mice as demonstrated by infection with Yersinia pseudotuberculosis in-frame deletion mutants. In addition, these five vag genes were essential only in vivo, since all the mutants were able to grow in vitro. These genes are broadly conserved among bacteria. Therefore, we propose that the corresponding vag gene products may constitute novel targets for antimicrobial therapy and that some vag mutants could serve as carrier strains for live vaccines.     

Essential genes are more evolutionarily conserved than are nonessential genes in bacteria

The "knockout-rate" prediction holds that essential genes should be more evolutionarily conserved than are nonessential genes. This is because negative (purifying) selection acting on essential genes is expected to be more stringent than that for nonessential genes, which are more functionally dispensable and/or redundant. However, a recent survey of evolutionary distances between Saccharomyces cerevisiae and Caenorhabditis elegans proteins did not reveal any difference between the rates of evolution for essential and nonessential genes. An analysis of mouse and rat orthologous genes also found that essential and nonessential genes evolved at similar rates when genes thought to evolve under directional selection were excluded from the analysis. In the present study, we combine genomic sequence data with experimental knockout data to compare the rates of evolution and the levels of selection for essential versus nonessential bacterial genes. In contrast to the results obtained for eukaryotic genes, essential bacterial genes appear to be more conserved than are nonessential genes over both relatively short (microevolutionary) and longer (macroevolutionary) time scales.