Thirty years of multiple sequence codes

An overview is presented on the status of studies on multiple codes in genetic sequences. Indirectly, the existence of multiple codes is recognized in the form of several rediscoveries of Second Genetic Code that is different each time. A due credit is given to earlier seminal work related to the codes often neglected in literature. The latest developments in the field of chromatin code are discussed, as well as perspectives of single-base resolution studies of nucleosome positioning, including rotational setting of DNA on the surface of the histone octamers.     

Identifying the ligated amino acid of archaeal tRNAs based on positions outside the anticodon

Proper recognition of tRNAs by their aminoacyl-tRNA synthetase is essential for translation accuracy. Following evidence that the enzymes can recognize the correct tRNA even when anticodon information is masked, we search for additional nucleotide positions within the tRNA molecule that potentially contain information for amino acid identification. Analyzing 3936 sequences of tRNA genes from 86 archaeal species, we show that the tRNAs’ cognate amino acids can be identified by the information embedded in the tRNAs’ nucleotide positions without relying on the anticodon information. We present a small set of six to 10 informative positions along the tRNA, which allow for amino acid identification accuracy of 90.6% to 97.4%, respectively. We inspected tRNAs for each of the 20 amino acid types for such informative positions and found that tRNA genes for some amino acids are distinguishable from others by as few as one or two positions. The informative nucleotide positions are in agreement with nucleotide positions that were experimentally shown to affect the loaded amino acid identity. Interestingly, the knowledge gained from the tRNA genes of one archaeal phylum does not extrapolate well to another phylum. Furthermore, each species has a unique ensemble of nucleotides in the informative tRNA positions, and the similarity between the sets of positions of two distinct species reflects their evolutionary distance. Hence, we term this set of informative positions a “tRNA cipher.” It is tempting to suggest that the diverging code identified here might also serve the aminoacyl tRNA synthetase in the task of tRNA recognition.     

The non-photosynthetic plastid in malarial parasites and other apicomplexans is derived from outside the green plastid lineage.

The discovery of a non-photosynthetic plastid genome in Plasmodium falciparum and other apicomplexans has provided a new drug target, but the evolutionary origin of the plastid has been muddled by the lack of characters, that typically define major plastid lineages. To clarify the ancestry of the plastid, we undertook a comprehensive analysis of all genomic characters shared by completely sequenced plastid genomes. Cladistic analysis of the pattern of plastid gene loss and gene rearrangements suggests that the apicomplexan plastid is derived from an ancestor outside of the green plastid lineage. Phylogenetic analysis of primary sequence data (DNA and amino acid characters) produces results that are generally independent of the analytical method, but similar genes (i.e., rpoB and rpoC) give similar topologies. The conflicting phylogenies in primary sequence data sets make it difficult to determine the the exact origin of the apicomplexan plastid and the apparent artifactual association of apicomplexan and euglenoid sequences suggests that DNA sequence data may be an inappropriate set of characters to address this phylogenetic question. At present we cannot reject our null hypothesis that the apicomplexan plastid is derived from a shared common ancestor between apicomplexans and dinoflagellates. During the analysis, we noticed that the Plasmodium tRNA-Met is probably tRNA-fMet and the tRNA-fMet is probably tRNA-Ile. We suggest that P. falciparum has lost the elongator type tRNA-Met and that similar to metazoan mitochondria there is only one species of methionine tRNA. In P. falciparum, this has been accomplished by recruiting the fMet-type tRNA to dually function in initiation and elongation. The tRNA-Ile has an unusual stem-loop in the variable region. The insertion in this region appears to have occurred after the primary origin of the plastid and further supports the monophyletic ancestory of plastids.     

《遗传学报》30年回顾与展望

《遗传学报》是中国遗传学会和中国科学院遗传与发育生物学研究所共同主办的高级学术刊物,中国自然科学核心期刊、中国科学院优秀期刊和全国优秀科技期刊,2001年被评为“中国期刊方阵双百期刊”,2002年获得“国家期刊奖重点科技期刊奖”。近年来,《遗传学报》由双月刊改为月刊,由小开本改为大开本,论文发表周期大为缩短。2002年得到的统计数据显示,《遗传学报》的各项指标均比上年增加。其中影响因子由0.605增至0.662;总被引频次由703次增至747次;基金论文比由0.80增至0.956;指标综合加权评分由62.71分增至65.887分。尤其是继美国化学文摘（CA）和医学索引（MED）收录之后,又被重要的检索系统美国生物学文摘（BA）和俄罗斯文摘杂志（PЖ）收录。     

基因组印记中的长非编码RNA

长非编码RNA(lnc RNA)是长度大于200 bp的一类非编码蛋白的RNA,因其在基因组中含量巨大以及重要的生物学功能引起了学术界的广泛关注.基因组印记是一种表观遗传现象,lnc RNAs通过建立靶基因的印记而发挥重要的生物功能.基因组印记可以用来研究lnc RNAs在转录和转录后水平调控基因表达的分子机制.本文选取6个印记机制研究比较透彻的印记区域,包括Kcnq1/Cdkn1c、Igf2r/Airn、Prader-Willi(PWS)/Angelman(AS)、Snurf/Snrpn、Dlk1-Dio3和H19/Igf2.通过介绍包括基因间lnc RNAs(H19、Ipw和Meg3)、反义lnc RNAs(Kcnq1ot1、Airn、Ube3a-ATS)和增强子lnc RNAs(IG-DMR e RNAs)在内的3种类型lnc RNAs在印记调控中的作用,从而了解lnc RNAs通过顺式或(/和)反式作用多种机制调控亲本特异性靶基因的表达.了解印记基因簇中lnc RNAs的作用方式将有助于我们揭示lnc RNAs在整个基因组中的作用机制.     

Sequence correlations between Cro recognition helices and cognate O(R) consensus half-sites suggest conserved rules of protein-DNA recognition

The O(R) regions from several lambdoid bacteriophages contain the three regulatory sites O(R)1, O(R)2 and O(R)3, to which the Cro and CI proteins can bind. These sites show imperfect dyad symmetry, have similar sequences, and generally lie on the same face of the DNA double helix. We have developed a computational method, which analyzes the O(R) regions of additional phages and predicts the location of these three sites. After tuning the method to predict known O(R) sites accurately, we used it to predict unknown sites, and ultimately compiled a database of 32 known and predicted O(R) binding site sets. We then identified sequences of the recognition helices (RH) for the cognate Cro proteins through manual inspection of multiple sequence alignments. Comparison of Cro RH and consensus O(R) half-site sequences revealed strong one-to-one correlations between two amino acids at each of three RH positions and two bases at each of three half-site positions (H1-->2, H3-->5 and H6-->6). In each of these three cases, one of the two amino acid/base-pairings corresponds to a contact observed in the crystal structure of a lambda Cro/consensus operator complex. The alternate amino acid/base combinations were rationalized using structural models. We suggest that the pairs of amino acid residues act as binary switches that efficiently modulate specificity for different consensus half-site variants during evolution. The observation of structurally reasonable amino acid-to-base correlations suggests that Cro proteins share some common rules of recognition despite their functional and structural diversity.     

脑循环功能检测技术近三十年进展

脑循环功能的异常改变往往早于形态学和影像学改变,这对于脑血管的早期检测以及治疗过程中疗效的评价有显著意义。国内外脑循环功能检测技术的发展已有30年左右的历史,本文综述了脑循环动力学参数的生理背景及脑循环功能检测技术近年来的发展。     

ChIA-PET技术

配对末端标签测序分析染色质相互作用(chromatin interaction analysis by paired-end tag sequencing,ChIA-PET)技术是一项在全基因组范围内分析远程染色质相互作用的新技术。它把染色质免疫沉淀(chromatin immunoprecipitation,ChIP)技术、染色质邻近式连接(chromatin proximity ligation)技术、配对末端标签(paired-endtag,PET)技术和新一代测序(next-generation sequencing)技术融为一体,在基因组三维折叠和套环状态下分析基因表达和调控。ChIA-PET技术已用于确定人乳腺腺癌细胞内雌激素受体a的结合位点之间的相互作用。随着更多蛋白质因子的发现及其抗体的应用,该技术可实时捕获全基因组范围内参与复制、转录过程的蛋白质因子结合位点以及结合位点间的相互作用,这对于阐明基因调控和疾病发生机制具有重大意义。     

Conversion of nucleotides sequences into genomic signals

An original tetrahedral representation of the Genetic Code (GC) that better describes its structure, degeneration and evolution trends is defined. The possibility to reduce the dimension of the representation by projecting the GC tetrahedron on an adequately oriented plane is also analyzed, leading to some equivalent complex representations of the GC. On these bases, optimal symbolic-to-digital mappings of the linear, nucleic acid strands into real or complex genomic signals are derived at nucleotide, codon and amino acid levels. By converting the sequences of nucleotides and polypeptides into digital genomic signals, this approach offers the possibility to use a large variety of signal processing methods for their handling and analysis. It is also shown that some essential features of the nucleotide sequences can be better extracted using this representation. Specifically, the paper reports for the first time the existence of a global helicoidal wrapping of the complex representations of the bases along DNA sequences, a large scale trend of genomic signals. New tools for genomic signal analysis, including the use of phase, aggregated phase, unwrapped phase, sequence path, stem representation of components'relative frequencies, as well as analysis of the transitions are introduced at the nucleotide, codon and amino acid levels, and in a multiresolution approach.     

Comparative study of some energetic and steric parameters of the wild type and mutants HIV-1 protease: a way to explain the viral resistance

Because, in vivo , the HIV-1 PR (HIV-1 protease) present a high mutation rate we performed a comparative study of the energetic behaviors of the wild type HIV-1 PR and four type of mutants: Val82/Asn; Val82/Asp; Gln7/Lys, Leu33/Ile, Leu63/Ile; Ala71/Thr, Val82/Ala. We suggest that the energetic fluctuation (electrostatic, van der Waals and torsion energy) of the mutants and the solvent accessible surface (SAS) values can be useful to explain the viral resistance process developed by HIV-1 PR. The number and localization of enzyme mutations induce important modifications of the van der Waals and torsional energy, while the electrostatic energy has an insignificant fluctuation. We showed that the viral resistance can be explored if the solvent accessible surfaces of the active site for the mutant structures are calculated. In this paper we have obtained the solvent accessible surface for a group of 15 mutants (11 mutants obtained by Protein Data Bank (PDB) file, 4 mutants modeled by CHARMM software) and for the wild type HIV-1 PR). Our study try to show that the number and localization of the mutations are factors which induce the HIV-1 PR viral resistance. The larger solvent accessible surface could be recorded for the point mutant Val 82/Phe.     

Dissecting Genetic Architecture Underlying Seed Traits in Multiple Environments

The seeds of flowering plants develop from double fertilization and play a vital role in reproduction and supplying human and animal food. The genetic variation of seed traits is influenced by multiple genetic systems, e.g., maternal, embryo, and/or endosperm genomes. Understanding the genetic architecture of seed traits is a major challenge because of this complex mechanism of multiple genetic systems, especially the epistasis within or between different genomes and their interactions with the environment. In this study, a statistical model was proposed for mapping QTL with epistasis and QTL-by-environment (QE) interactions underlying endosperm and embryo traits. Our model integrates the maternal and the offspring genomes into one mapping framework and can accurately analyze maternal additive and dominant effects, endosperm/embryo additive and dominant effects, and epistatic effects of two loci in the same or two different genomes, as well as interaction effects of each genetic component of QTL with environment. Intensive simulations under different sampling strategies, heritabilities, and model parameters were performed to investigate the statistical properties of the model. A set of real cottonseed data was analyzed to demonstrate our methods. A software package, QTLNetwork-Seed-1.0.exe, was developed for QTL analysis of seed traits.