5-HTR2A基因 102T/C多态性与精神分裂症的相关性研究

目的 :探讨5 -羟色胺2A受体(5 -HTR2A)基因102T/C的多态性与精神分裂症的关系。方法 :应用PCR -RFLP技术 ,在90名无亲缘关系的大理地区正常汉族人和80名精神分裂症患者中对5 -羟色胺受体基因102T/C多态性进行分析。结果 :在正常对照组和精神分裂症组之间 ,等位基因频率 ( χ2=0.01,P>0.05)和各种基因型 (P值均大于0.05)分布无显著性差异。结论 :5 -羟色胺受体基因102C/T的多态性与汉族人群精神分裂症不相关。     

Bioinformatic prediction of selenoprotein genes in the dolphin genome

Selenium (Se), an essential trace element in vivo, is present mainly as selenocystein (Sec) in various selenoproteins. The Sec residue is translated from an in-frame TGA codon, which traditionally functions as a stop codon. Prediction of selenoprotein genes is difficult due to the lack of an effective method for distinguishing the dual function of the TGA codon in the open reading frame of a selenoprotein gene. In this article a eukaryotic bioinformatic prediction system that we have developed was used to predict selenoprotein genes from the genome of the common bottlenose dolphin, Tursiops truncatus. Sixteen selenoprotein genes were predicted, including selenoprotein P and glutathione peroxidase. In particular, a type II iodothyronine deiodinase was found to have two Sec residues, while the type I iodothyronine deiodinase gene has two alternative splice forms. These results provide important information for the investigation of the relationship between a variety of selenoproteins and the evolution of the marine-living dolphin.     

Pt／MgO体系中金属—担体相互作用的TPD和XPS研究

本文对铂担载于两种不同来源和制备历史的MgO上的体系(A:MgO 99.5%,BET表面积33m~2/g,B:MgO 99.999%,BET表面积9m~2/g)在低温(573K,LTR)和高温(773K HTR)还原后的H_2化学吸附、TPD和XPS等行为进行了考察。结果表明,体系A在HTR后发生了强相互作用,而B却未观察到类似的作用,A、B体系的LTR后和HTR后的脱附峰温基本一致,分别为388±5K,536±3K(LTR)和710±5K(HTR);来发现LTR和HTR后Pt4f_(7/2)的变化,也未发现表面杂质元素;A体系低温还原后的XPS较之B体系在533.5eV处多出了一个肩峰,可标识为表面OH基团。以上事实说明,所研究体系的金属—担体强相互作用与金属—担体间的电子转移,担体的迁移,高温还原后的储氢现象或生成的含氢物种等无关联关系,而表面OH的存在是所研究的体系产生强相互作用的可能原因。     

Structural basis for translation termination on the 70S ribosome

At termination of protein synthesis, type I release factors promote hydrolysis of the peptidyl-transfer RNA linkage in response to recognition of a stop codon. Here we describe the crystal structure of the Thermus thermophilus 70S ribosome in complex with the release factor RF1, tRNA and a messenger RNA containing a UAA stop codon, at 3.2 A resolution. The stop codon is recognized in a pocket formed by conserved elements of RF1, including its PxT recognition motif, and 16S ribosomal RNA. The codon and the 30S subunit A site undergo an induced fit that results in stabilization of a conformation of RF1 that promotes its interaction with the peptidyl transferase centre. Unexpectedly, the main-chain amide group of Gln 230 in the universally conserved GGQ motif of the factor is positioned to contribute directly to peptidyl-tRNA hydrolysis.     

Expression of peptide chain release factor 2 requires high-efficiency frameshift

Peptide chain release factors are soluble proteins that participate in the stop codon-dependent termination of polypeptide biosynthesis. In Escherichia coli, two release factors are necessary for peptide chain termination: release factor 1 (RF1) specifies UAG- and UAA-dependent termination whereas release factor 2 (RF2) specifies UGA- and UAA-dependent termination. Release factors are found in low concentrations relative to other translation factors, suggesting that their expression is tightly regulated and, accordingly, making the study of their structure-function relationship difficult. RF1 and RF2 exhibit significant sequence homology, probably reflecting their similar functions and perhaps a common evolutionary origin. DNA and peptide sequencing have suggested the existence of a unique mechanism for the autogenous regulation of RF2 in which an in-frame UGA stop codon requires an obligatory +1 frameshift within the coding region of the RF2 gene. In this report we present in vitro experimental results consistent with the autogenous regulation of RF2. Additionally, we used RF2-lacZ gene fusions to demonstrate that autogenous regulation occurs, at least in part, by premature termination at the in-frame stop codon, since deletion of this stop codon leads to overproduction of the RF2-LacZ fusion protein. Frameshifting at this premature termination codon occurs at the remarkably high rate of 50%.     

Identification of a novel translation factor necessary for the incorporation of selenocysteine into protein

During the biosynthesis of selenoproteins in both prokaryotes and eukaryotes, selenocysteine is cotranslationally incorporated into the nascent polypeptide chain through a process directed by a UGA codon that normally functions as a stop codon. Recently, four genes have been identified whose products are required for selenocysteine incorporation in Escherichia coli. One of these genes, selC, codes for a novel transfer RNA species (tRNAUCA) that accepts serine and cotranslationally inserts selenocysteine by recognizing the specific UGA codon. The serine residue attached to this tRNA is converted to selenocysteine in a reaction dependent on functional selA and selD gene products. By contrast, the selB gene product (SELB) is not required until after selenocysteyl-tRNA biosynthesis. Here we present evidence indicating that SELB is a novel translation factor. The deduced amino-acid sequence of SELB exhibits extensive homology with the sequences of the translation initiation factor-2 (IF-2) and elongation factor Tu (EF-Tu). Furthermore, purified SELB protein binds guanine nucleotides in a 1:1 molar ratio and specifically complexes selenocysteyl-tRNAUCA, but does not interact with seryl-tRNAUCA. Thus, SELB could be an amino acid-specific elongation factor, replacing EF-Tu in a special translational step.     

Analysis of synonymous codon usage and evolution of begomoviruses

Begomoviruses are single-stranded DNA viruses and cause severe diseases in major crop plants worldwide. Based on current genome sequence analyses, we found that synonymous codon usage variations in the protein-coding genes of begomoviruses are mainly influenced by mutation bias. Base composition analysis suggested that the codon usage bias of AV1 and BV1 genes is significant and their expressions are high. Fourteen codons were determined as translational optimal ones according to the comparison of codon usage patterns between highly and lowly expressed genes. Interestingly the codon usages between begomoviruses from the Old and the New Worlds are apparently different, which supports the idea that the bipartite begomoviruses of the New World might originate from bipartite ones of the Old World, whereas the latter evolve from the Old World monopartite begomoviruses.     

蛋白质编码区碱基分布与终止密码子的关系

对11种具有不同G C含量的微生物基因组蛋白质编码区进行统计分析，结果显示蛋白质编码区3个密码子位碱基分布具有明显的不对称性，与终止密码子对应的一些单、双核苷酸出现的频率很低，由此得出结论：终止密码子对编码区碱基的使用起重要限制作用．     

The joining of ribosomal subunits in eukaryotes requires eIF5B

Initiation of eukaryotic protein synthesis begins with the ribosome separated into its 40S and 60S subunits. The 40S subunit first binds eukaryotic initiation factor (eIF) 3 and an eIF2-GTP-initiator transfer RNA ternary complex. The resulting complex requires eIF1, eIF1A, eIF4A, eIF4B and eIF4F to bind to a messenger RNA and to scan to the initiation codon. eIF5 stimulates hydrolysis of eIF2-bound GTP and eIF2 is released from the 48S complex formed at the initiation codon before it is joined by a 60S subunit to form an active 80S ribosome. Here we show that hydrolysis of eIF2-bound GTP induced by eIF5 in 48S complexes is necessary but not sufficient for the subunits to join. A second factor termed eIF5B (relative molecular mass 175,000) is essential for this process. It is a homologue of the prokaryotic initiation factor IF2 (re and, like it, mediates joining of subunits and has a ribosome-dependent GTPase activity that is essential for its function.     

MHC II DRB variation and trans-species polymorphism in the golden snub-nosed monkey (Rhinopithecus roxellana)

Genetic variation is generally believed to be important in studying endangered species’ adaptive potential.Early studies assessed genetic diversity using nearly neutral markers,such as microsatellite loci and mitochondrial DNA(mtDNA),which are very informative for phylogenetic and phylogeographic reconstructions.However,the variation at these loci cannot provide direct information on selective processes involving the interaction of individuals with their environment,or on the capability to resist continuously evolving pathogens and parasites.The importance of genetic diversity at informative adaptive markers,such as major histocompatibility complex(MHC) genes,is increasingly being realized,especially in endangered,isolated species.Small population size and isolation make the golden snub-nosed monkey(Rhinopithecus roxellana) particularly susceptible to genetic variation losses through inbreeding and restricted gene flow.In this study,we compared the genetic variation and population structure of microsatellites,mtDNA,and the most relevant adaptive region of the MHC II-DRB genes in the golden snub-nosed monkey.We examined three Chinese R.roxellana populations and found the same variation patterns in all gene regions,with the population from Shennongjia population,Hubei Province,showing the lowest polymorphism among three populations.Genetic drift that outweighed balancing selection and the founder effect in these populations may explain the similar genetic variation pattern found in these neutral and adaptive genes.     

Structure of the Escherichia coli ribosomal termination complex with release factor 2

Termination of protein synthesis occurs when the messenger RNA presents a stop codon in the ribosomal aminoacyl (A) site. Class I release factor proteins (RF1 or RF2) are believed to recognize stop codons via tripeptide motifs, leading to release of the completed polypeptide chain from its covalent attachment to transfer RNA in the ribosomal peptidyl (P) site. Class I RFs possess a conserved GGQ amino-acid motif that is thought to be involved directly in protein-transfer-RNA bond hydrolysis. Crystal structures of bacterial and eukaryotic class I RFs have been determined, but the mechanism of stop codon recognition and peptidyl-tRNA hydrolysis remains unclear. Here we present the structure of the Escherichia coli ribosome in a post-termination complex with RF2, obtained by single-particle cryo-electron microscopy (cryo-EM). Fitting the known 70S and RF2 structures into the electron density map reveals that RF2 adopts a different conformation on the ribosome when compared with the crystal structure of the isolated protein. The amino-terminal helical domain of RF2 contacts the factor-binding site of the ribosome, the 'SPF' loop of the protein is situated close to the mRNA, and the GGQ-containing domain of RF2 interacts with the peptidyl-transferase centre (PTC). By connecting the ribosomal decoding centre with the PTC, RF2 functionally mimics a tRNA molecule in the A site. Translational termination in eukaryotes is likely to be based on a similar mechanism.     

大肠杆菌和枯草杆菌的L-ter 到起始密码子的距离分析

基于第一ATG规则，分别对确定基因和不确定基因的L-ter到起始密码子(ATG、GTG或TTG)的距离和L-ter到起始密码子下游紧邻的ATG的距离进行统计，结果表明：L-ter到起始密码子的距离主要分布在20个氨基酸以内；在以第一ATG和第一GTG为起始密码子的基因中，L-ter到起始密码子下游紧邻的ATG是L-ter到起始密码子平均距离的4～5倍。这些可能是起始密码子的重要位置特征，也说明了少数基因以GTG起始的原因．对于不满足第一ATG、GTG规则的基因，分析了L-ter到起始密码子之间出现ATG、GTG和TTG的比率，发现大肠杆菌的不确定基因与确定基因之间有较大的差别，而枯草杆菌的差别不大．     

Inference of human population history from individual whole-genome sequences

The history of human population size is important for understanding human evolution. Various studies have found evidence for a founder event (bottleneck) in East Asian and European populations, associated with the human dispersal out-of-Africa event around 60 thousand years (kyr) ago. However, these studies have had to assume simplified demographic models with few parameters, and they do not provide a precise date for the start and stop times of the bottleneck. Here, with fewer assumptions on population size changes, we present a more detailed history of human population sizes between approximately ten thousand and a million years ago, using the pairwise sequentially Markovian coalescent model applied to the complete diploid genome sequences of a Chinese male (YH), a Korean male (SJK), three European individuals (J. C. Venter, NA12891 and NA12878 (ref. 9)) and two Yoruba males (NA18507 (ref. 10) and NA19239). We infer that European and Chinese populations had very similar population-size histories before 10-20?kyr ago. Both populations experienced a severe bottleneck 10-60?kyr ago, whereas African populations experienced a milder bottleneck from which they recovered earlier. All three populations have an elevated effective population size between 60 and 250?kyr ago, possibly due to population substructure. We also infer that the differentiation of genetically modern humans may have started as early as 100-120?kyr ago, but considerable genetic exchanges may still have occurred until 20-40?kyr ago.     

Asymmetric leaves1 mediates leaf patterning and stem cell function in Arabidopsis

Meristem function in plants requires both the maintenance of stem cells and the specification of founder cells from which lateral organs arise. Lateral organs are patterned along proximodistal, dorsoventral and mediolateral axes. Here we show that the Arabidopsis mutant asymmetric leaves1 (as1) disrupts this process. AS1 encodes a myb domain protein, closely related to PHANTASTICA in Antirrhinum and ROUGH SHEATH2 in maize, both of which negatively regulate knotted-class homeobox genes. AS1 negatively regulates the homeobox genes KNAT1 and KNAT2 and is, in turn, negatively regulated by the meristematic homeobox gene SHOOT MERISTEMLESS. This genetic pathway defines a mechanism for differentiating between stem cells and organ founder cells within the shoot apical meristem and demonstrates that genes expressed in organ primordia interact with meristematic genes to regulate shoot morphogenesis.     

13种哺乳动物OTR密码子使用偏性及其聚类分析

目的研究13种哺乳动物催产素受体基因(OTR)密码子使用偏性,并探讨其影响因素;通过对偏性情况进行聚类分析,研究其与系统发育的关系.方法计算RSCU,CBI,ENC等密码子偏性指标,与可能的几种影响因素做相关性分析,采用SPASS 15.0软件,以相对同义密码子使用度为变量对偏性情况进行聚类分析.结果与结论 1)CUG,GUG,GCC,UUC,AUC,CGC为哺乳动物OTR使用频率较高的密码子;2)密码子第3位碱基的GC含量是影响哺乳动物OTR密码子偏性的主要因素,基因的GC含量次之,而芳香族氨基酸的含量和蛋白疏水水平对其密码子使用偏性的影响不大;3)对于功能相同的基因,亲缘关系相近的物种密码子使用偏性指标较接近,但某些物种仍有一定差异.     

Genetic basis of BCG-induced suppression of delayed hypersensitivity

BCG can either act as an adjuvant to potentiate immunological responses or, in some cases, can induce suppression. The reasons for these differential activities are not clear but may include routes and doses of administration, as well as variable host reactivity to the agent. In this study, we have used killed BCG administered intravenously to produce chronic granulomatous inflammation (CGI) in the lungs and spleen of inbred mice. We report that strains which develop CGI were usually anergic, as evaluated by the development of delayed hypersensitivity (DH) to sheep erythrocytes (SRBC). Studies on the genetics of BCG-induced anergy indicated that it was unigenic, recessive and linked (approximately 28 recombination units) to the immunoglobulin heavy-chain allotype (Igh). There was no influence by genes linked to the major histocompatibility complex. The study indicates that anergy associated with CGI is under genetic control, which may explain the variability of anergy in patients with granulomatous diseases. The implication of linkage to the Igh complex is not clear, but it may be associated with VH receptors on T lymphocytes, which in turn act on macrophages to mediate suppression.     

Gompertz模型的成年种群脉冲优化收获策略

研究了Gompertz模型的成年种群脉冲优化收获问题,证明了系统的正周期解的全局渐进稳定性,得到了系统的单位时间最大持续捕获量、最优捕获努力量,以及相应的最优群水平和正周期解.     

Predicting disease genes for familial dilated cardiomyopathy based on the codon usage bias

Familial dilated cardiomyopathy （FDC） is a common monogenic disease mostly with autosomal dominant inheritance. Fifteen different loci for autosomal dominant FDC have been mapped; however, only eight FDC genes have been found, and it is still a big challenge to identify additional seven FDC genes in their chromosomal regions. We found that the codon usage frequencies in most of known FDC gene sequences are consistently biased, and significantly different from the average codon usage frequencies of human genes. This unique feature of codon usage was used to develop a novel approach to predicting FDC genes. Leave-oneout cross-validation results demonstrate that this approach can effectively detect FDC genes from numbers of genes in their chromosomal regions. Another advantage of this approach is that it is solely based on DNA sequences and therefore has the ability to identify potential FDC genes whose functions are completely unknown. Further, this approach has been used to analyze the seven FDC loci in which the FDC genes are still unknown. Both the detailed prediction results and the prediction program are available at http：// infosci.hust.edu.cn, which might provide help for relevant experimental researches to find new FDC genes.     

三七-白及药对作用机制的网络药理学分析

通过网络药理学的方法,研究三七-白及药对在疾病治疗过程中潜在的药理作用机制.采用TCMSP数据库筛选三七-白及药对的活性成分和作用靶点,并用Uniprot数据库校正靶点信息得到靶点基因,利用CTD数据库获得靶点基因相关的疾病类型,通过STRING数据库构建靶点蛋白相互作用网络,分析得到核心蛋白,运用DAVID数据库富集分析靶点基因参与的基因本体论(GO)生物学过程及京都基因与基因百科全书(KEGG)通路.共筛选得到17个活性成分,涉及193个作用靶点.结果表明:槲皮素、β-谷甾醇和豆甾醇的作用靶点数目最多;靶点基因与35类疾病相关,主要包括癌症、神经系统疾病、心血管疾病等;蛋白相互作用网络分析得到核心蛋白AKT1,MAPK1,c-Jun,P53,TNF等;靶点基因主要涉及药物反应,RNA聚合酶Ⅱ启动子转录的正调控等91条GO生物学过程,KEGG通路显著富集到癌症通路、乙型肝炎等66条通路,与前述疾病分析结果相符.     

A cryo-electron microscopic study of ribosome-bound termination factor RF2

Protein synthesis takes place on the ribosome, where genetic information carried by messenger RNA is translated into a sequence of amino acids. This process is terminated when a stop codon moves into the ribosomal decoding centre (DC) and is recognized by a class-1 release factor (RF). RFs have a conserved GGQ amino-acid motif, which is crucial for peptide release and is believed to interact directly with the peptidyl-transferase centre (PTC) of the 50S ribosomal subunit. Another conserved motif of RFs (SPF in RF2) has been proposed to interact directly with stop codons in the DC of the 30S subunit. The distance between the DC and PTC is approximately 73 A. However, in the X-ray structure of RF2, SPF and GGQ are only 23 A apart, indicating that they cannot be at DC and PTC simultaneously. Here we show that RF2 is in an open conformation when bound to the ribosome, allowing GGQ to reach the PTC while still allowing SPF-stop-codon interaction. The results indicate new interpretations of accuracy in termination, and have implications for how the presence of a stop codon in the DC is signalled to PTC.