MADS-box基因家族基因重复及其功能的多样性

基因的重复(duplication)及其功能的多样性(diversification)为生物体新的形态进化提供了原材料。MADS-box基因在植物(特别是被子植物)的进化过程中发生了大规模的基因重复事件而形成一个多基因家族。MADS-box基因家族的不同成员在植物生长发育过程中起着非常重要的作用,在调控开花时间、决定花分生组织和花器官特征以及调控根、叶、胚珠及果实的发育中起着广泛的作用。探讨MADS-box基因家族的进化历史有助于深入了解基因重复及随后其功能分化的过程和机制。本文综述了MADS-box基因家族基因重复及其功能分化式样的研究进展。     

PaGenBase: A Pattern Gene Database for the Global and Dynamic Understanding of Gene Function

Pattern genes are a group of genes that have a modularized expression behavior under serial physiological conditions. The identification of pattern genes will provide a path toward a global and dynamic understanding of gene functions and their roles in particular biological processes or events, such as development and pathogenesis. In this study, we present PaGenBase, a novel repository for the collection of tissue- and time-specific pattern genes, including specific genes, selective genes, housekeeping genes and repressed genes. The PaGenBase database is now freely accessible at http://bioinf.xmu.edu.cn/PaGenBase/. In the current version (PaGenBase 1.0), the database contains 906,599 pattern genes derived from the literature or from data mining of more than 1,145,277 gene expression profiles in 1,062 distinct samples collected from 11 model organisms. Four statistical parameters were used to quantitatively evaluate the pattern genes. Moreover, three methods (quick search, advanced search and browse) were designed for rapid and customized data retrieval. The potential applications of PaGenBase are also briefly described. In summary, PaGenBase will serve as a resource for the global and dynamic understanding of gene function and will facilitate high-level investigations in a variety of fields, including the study of development, pathogenesis and novel drug discovery.     

Multivariate Gene Selection and Testing in Studying the Exposure Effects on a Gene Set

Studying the association between a gene set (e.g., pathway) and exposures using multivariate regression methods is of increasing importance in genomic studies. Such an analysis is often more powerful and interpretable than individual-gene analysis. Since many genes in a gene set are likely not affected by exposures, one is often interested in identifying a subset of genes in the gene set that are affected by exposures. This allows for better understanding of the underlying biological mechanism and for pursuing further biological investigation of these genes. The selected subset of ??signal?? genes also provides an attractive vehicle for a more powerful test for the association between the gene set and exposures. We propose two computationally simple Canonical Correlation Analysis (CCA) based variable selection methods: Sparse Outcome Selection (SOS) CCA and step CCA, to jointly select a subset of genes in a gene set that are associated with exposures. Several model selection criteria, such as BIC and the new Correlation Information Criterion (CIC), are proposed and compared. We also develop a global test procedure for testing the exposure effects on the whole gene set, accounting for gene selection. Through simulation studies, we show that the proposed methods improve upon an existing method when the genes are correlated and are more computationally efficient. We apply the proposed methods to the analysis of the Normative Aging DNA methylation Study to examine the effects of airborne particular matter exposures on DNA methylations in a genetic pathway.     

Evolution of the Growth Hormone Gene Family

SYNOPSIS. Growth hormone, prolactin and chorionic somatomammotropin(placental lactogen) area family of hormones that are relatedby function, immunochemistry and structure. Because of the structuralsimilarities between these hormones, it was proposed that thecorresponding genes were derived from a common precursor geneby duplication and sequence divergence. Comparisons of the mRNAsequences and chromosomal genes for these hormones from severalspecies provide additional support for the model of their commonancestry and indications of how the precursor genewas formed.The diversification of these three genes has involved changesin codon choices thataffect the overall G-C content of the genes,alterations in the sizes of introns with conservedexon-intronboundaries and concerted evolutionary mechanisms with duplicatedgrowth hormone andhorionic somatomammotropin genes in humans.The precursor gene appears to have evolved by the fourfold duplicationof one exon element and the separate insertion of an exon encodinga different protein domain. Finally, there also appears to havebeen the separate insertion of sequences containing a promoterelement and a potential glucocorticoid regulatory element.     

Gene Duplication and Gene Conversion in the Caenorhabditis elegans Genome

A comprehensive analysis of duplication and gene conversion for 7394 Caenorhabditis elegans genes (about half the expected total for the genome) is presented. Of the genes examined, 40% are involved in duplicated gene pairs. Intrachromosomal or cis gene duplications occur approximately two times more often than expected. In general the closer the members of duplicated gene pairs are, the more likely it is that gene orientation is conserved. Gene conversion events are detectable between only 2% of the duplicated pairs. Even given the excesses of cis duplications, there is an excess of gene conversion events between cis duplicated pairs on every chromosome except the X chromosome. The relative rates of cis and trans gene conversion and the negative correlation between conversion frequency and DNA sequence divergence for unconverted regions of converted pairs are consistent with previous experimental studies in yeast. Three recent, regional duplications, each spanning three genes are described. All three have already undergone substantial deletions spanning hundreds of base pairs. The relative rates of duplication and deletion may contribute to the compactness of the C. elegans genome. Received: 30 July 1998 / Accepted: 12 October 1998     

Gene dispensability

Genome-wide mutagenesis studies indicate that up to about 90% of genes in bacteria and 80% in eukaryotes can be inactivated individually leaving an organism viable, often seemingly unaffected. Several strategies are used to learn what these apparently dispensable genes contribute to fitness. Assays of growth under hundreds of physical and chemical stresses are among the most effective experimental approaches. Comparative studies of genomic DNA sequences continue to be valuable in discriminating between the core bacterial genome and the more variable niche-specific genes. The concept of the core genome appears currently unfeasible for eukaryotes but progress has been made in understanding why they contain numerous gene duplicates.     

Gene Circuit Analysis of the Terminal Gap Gene huckebein

The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.     

Complete Characterization of the Human ABC Gene Family

The human ATP-binding cassette (ABC) transporters comprise a large family of membrane transport proteins and play a vital role in many cellular processes. The genes provide functions as diverse as peptide transport, cholesterol and sterol transport, bile acid, retinoid, and iron transport. In addition some ABC genes play a role as regulatory elements. Many ABC genes play a role in human genetic diseases, and several are critical drug transport proteins overexpressed in drug resistant cells. Analysis of the gene products allows the genes to be grouped into seven different subfamilies.     

植物GH3基因家族研究进展

生长素在植物的整个生长发育过程中都具有重要的作用,其早期响应基因可归为3类:Aux/IAAs、GH3s、SAURs.通过功能基因组学的研究,特别是对相关突变体的分子遗传学与分子生物学的研究,使我们对这些基因家族的作用机理的理解更为深入.以下综述了植物GH3基因的结构、功能及表达调控模式,重点介绍了由GH3介导的生长素信号途径与其他信号转导途径之间的互作和GH3基因与植物逆境胁迫适应的关系.     

MADS-box 基因家族基因重复及其功能的多样性

基因的重复(duplication)及其功能的多样性(diversification)为生物体新的形态进化提供了原材料。MADS-box基因在植物(特别是被子植物)的进化过程中发生了大规模的基因重复事件而形成一个多基因家族。MADS-box基因家族的不同成员在植物生长发育过程中起着非常重要的作用, 在调控开花时间、决定花分生组织和花器官特征以及调控根、叶、胚珠及果实的发育中起着广泛的作用。探讨MADS-box基因家族的进化历史有助于深入了解基因重复及随后其功能分化的过程和机制。本文综述了MADS-box基因家族基因重复及其功能分化式样的研究进展。     

Multiple Gene Duplication and Rapid Evolution in the groEL Gene: Functional Implications

The chaperonins, GroEL and GroES, are present ubiquitously and provide a paradigm in the understanding of assisted protein folding. Due to its essentiality of function, GroEL exhibits high sequence conservation across species. Complete genome sequencing has shown the occurrence of duplicate or multiple copies of groEL genes in bacteria such as Mycobacterium tuberculosis and Corynebacterium glutamicum. Monophyly of each bacterial clade in the phylogenetic tree generated for the GroEL protein suggests a lineage-specific duplication. The duplicated groEL gene in Actinobacteria is not accompanied by the operonic groES despite the presence of upstream regulatory elements. Our analysis suggests that in these bacteria the duplicated groEL genes have undergone rapid evolution and divergence to function in a GroES-independent manner. Evaluation of multiple sequence alignment demonstrates that the duplicated genes have acquired mutations at functionally significant positions including those involved in substrate binding, ATP binding, and GroES binding and those involved in inter-ring and intra-ring interactions. We propose that the duplicate groEL genes in different bacterial clades have evolved independently to meet specific requirements of each clade. We also propose that the groEL gene, although essential and conserved, accumulates nonconservative substitutions to exhibit structural and functional variations. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. [Reviewing Editor: Dr. Debashish Bhattacharya]     

Gene Expression Analysis

The response of cells to extracellular signals usually requires altered expression of many genes, possibly including several distinct metabolic pathways. In some cases, only a subset of genes involved in such responses are known, which requires techniques to analyze changes in the expression of multiple genes, both known and unknown. Three techniques, two‐dimensional gel electrophoresis, differential display, and gene discovery arrays, provide opportunities for measuring changes in gene expression levels, as well as for identifying novel gene products.     

Gene Structure Prediction Using an Orthologous Gene of Known Exon-Intron Structure

Given the availability of complete genome sequences from related organisms, sequence conservation can provide important clues for predicting gene structure. In particular, one should be able to leverage information about known genes in one species to help determine the structures of related genes in another. Such an approach is appealing in that high-quality gene prediction can be achieved for newly sequenced species, such as mouse and puffer fish, using the extensive knowledge that has been accumulated about human genes. This article reports a novel approach to predicting the exon-intron structures of mouse genes by incorporating constraints from orthologous human genes using techniques that have previously been exploited in speech and natural language processing applications. The approach uses a context-free grammar to parse a training corpus of annotated human genes. A statistical training procedure produces a weighted recursive transition network (RTN) intended to capture the general features of a mammalian gene. This RTN is expanded into a finite state transducer (FST) and composed with an FST capturing the specific features of the human orthologue. This model includes a trigram language model on the amino acid sequence as well as exon length constraints. A final stage uses the free software package ClustalW to align the top n candidates in the search space. For a set of 98 orthologous human-mouse pairs, we achieved 96% sensitivity and 97% specificity at the exon level on the mouse genes, given only knowledge gleaned from the annotated human genome.     

融合基因关系网和功能预测恶性胶质瘤基因方法研究

目的:建立挖掘恶性胶质瘤候选基因的方法并进行系统分析。方法:结合恶性胶质瘤已知通路内基因和发生点突变和拷贝数改变的基因构建扩展基因关系网络,计算并分别寻找在网络中度和中心性得分高,脆弱性为正数的节点(基因),将满足一种或多种测度并与已知恶性胶质瘤基因共功能的基因作为恶性胶质瘤候选基因。最后,通过文献验证方法评价多种测度预测恶性胶质瘤基因的效能。结果:融合基因功能后,利用基因在网络中的度和脆弱性可识别大部分恶性胶质瘤基因,但利用中心性预测的结果较差;当将三个测度融合后,效能并没比单独使用脆弱性高。结论:融合基因功能关系和网络脆弱性是预测恶性胶质瘤基因的最佳测度。     

Phylogenomic Analysis of the PEBP Gene Family in Cereals

The TFL1 and FT genes, which are key genes in the control of flowering time in Arabidopsis thaliana, belong to a small multigene family characterized by a specific phosphatidylethanolamine-binding protein domain, termed the PEBP gene family. Several PEBP genes are found in dicots and monocots, and act on the control of flowering time. We investigated the evolution of the PEBP gene family in cereals. First, taking advantage of the complete rice genome sequence and EST databases, we found 19 PEBP genes in this species, 6 of which were not previously described. Ten genes correspond to five pairs of paralogs mapped on known duplicated regions of the rice genome. Phylogenetic analysis of Arabidopsis and rice genes indicates that the PEBP gene family consists of three main homology classes (the so-called TFL1-LIKE, MFT-LIKE, and FT-LIKE subfamilies), in which gene duplication and/or loss occurred independently in Arabidopsis and rice. Second, phylogenetic analyses of genomic and EST sequences from five cereal species indicate that the three subfamilies of PEBP genes have been conserved in cereals. The tree structure suggests that the ancestral grass genome had at least two MFT-like genes, two TFL1-like genes, and eight FT-like genes. A phylogenomic approach leads to some hypotheses about conservation of gene function within the subfamilies. [Reviewing Editor: Dr. Yves Van de Peer]