A four-base paired genetic helix with expanded size

We describe a new molecular class of genetic-pairing system that has a native DNA backbone but has all four base pairs replaced by new, larger pairs. The base pairs include size-expanded analogs of thymine and of adenine, both extended by the width of a benzene ring (2.4 A). The expanded-diameter double helices are more thermodynamically stable than the Watson-Crick helix, likely because of enhanced base stacking. Structural data confirm a right-handed, double-stranded, and base-paired helical form. Because of the larger base size, all the pairs of this helical system are fluorescent, which suggests practical applications in detection of natural DNA and RNA. Our findings establish that there is no apparent structural or thermodynamic prohibition against genetic systems having sizes different from the natural one.     

Expanding the genetic code of Escherichia coli

A unique transfer RNA (tRNA)/aminoacyl-tRNA synthetase pair has been generated that expands the number of genetically encoded amino acids in Escherichia coli. When introduced into E. coli, this pair leads to the in vivo incorporation of the synthetic amino acid O-methyl-l-tyrosine into protein in response to an amber nonsense codon. The fidelity of translation is greater than 99%, as determined by analysis of dihydrofolate reductase containing the unnatural amino acid. This approach should provide a general method for increasing the genetic repertoire of living cells to include a variety of amino acids with novel structural, chemical, and physical properties not found in the common 20 amino acids.     

Expanding the genetic code of Escherichia coli with phosphoserine

O-Phosphoserine (Sep), the most abundant phosphoamino acid in the eukaryotic phosphoproteome, is not encoded in the genetic code, but synthesized posttranslationally. Here, we present an engineered system for specific cotranslational Sep incorporation (directed by UAG) into any desired position in a protein by an Escherichia coli strain that harbors a Sep-accepting transfer RNA (tRNA(Sep)), its cognate Sep-tRNA synthetase (SepRS), and an engineered EF-Tu (EF-Sep). Expanding the genetic code rested on reengineering EF-Tu to relax its quality-control function and permit Sep-tRNA(Sep) binding. To test our system, we synthesized the activated form of human mitogen-activated ERK activating kinase 1 (MEK1) with either one or two Sep residues cotranslationally inserted in their canonical positions (Sep(218), Sep(222)). This system has general utility in protein engineering, molecular biology, and disease research.     

Structural basis of RNA-dependent recruitment of glutamine to the genetic code

Glutaminyl-transfer RNA (Gln-tRNA(Gln)) in archaea is synthesized in a pretranslational amidation of misacylated Glu-tRNA(Gln) by the heterodimeric Glu-tRNA(Gln) amidotransferase GatDE. Here we report the crystal structure of the Methanothermobacter thermautotrophicus GatDE complexed to tRNA(Gln) at 3.15 angstroms resolution. Biochemical analysis of GatDE and of tRNA(Gln) mutants characterized the catalytic centers for the enzyme's three reactions (glutaminase, kinase, and amidotransferase activity). A 40 angstrom-long channel for ammonia transport connects the active sites in GatD and GatE. tRNA(Gln) recognition by indirect readout based on shape complementarity of the D loop suggests an early anticodon-independent RNA-based mechanism for adding glutamine to the genetic code.     

An expanded approach to the problem of disappearing species

Assistance for disappearing species is at present too localized and dispersed to make much impact on the problem with its growing dimensions. Species are threatened primarily because of their status as common property. Institutional deficiencies, notably those of free markets and property rights, promote depletion of species. Conversely, present institutional mechanisms offer little scope for society to express its preferences for goods without price or to establish responsibility for common-heritage resources. The situation postulates corrective measures on the part of collective authority at the international level. These measures would require a joint commitment by the developed and developing worlds, on a scale to reflect the increasingly interdependent needs and opportunities of the community at large. Whether the community perceives itself as a community or not, it functions as such in many of its ecological relationships and economic interactions. The community will sooner or later be obliged to respond to the problem of vanishing species: either sooner, through protective measures of sufficient scope, or later, when it finds that the disappearance of large numbers of species represents a loss through which it is indivisibly impoverished.     

一种基于卷积码模型的遗传序列分析方法

【目的】研究通信纠错编码理论在生物学领域研究中的应用。【方法】基于纠错编码理论,将卷积码模型分析方法用于遗传序列的分析,结合密码子简并性以及碱基关联短程为主的特性,对卷积码模型的生成矩阵、编码长度和约束长度等参数进行讨论。对2种原核生物(Escherichia colistr.K-12 substr.MG1655和Staphylococcus epidermidisATCC 12228)与2种真核生物(Arabidopsis thaliana chromosome 4和Oryza sativa(japonica cultivar-group)chromosome 10)DNA序列翻译起始及终止的特征进行分析,并通过对不同卷积码模型的比较,确定合适的分析模型。【结果】在适当的分析模型下,分析结果在开放阅读框(ORF)起始端和终止端附近,显示出与起始密码子和终止密码子位置紧密关联的明显码距变化,而不适当的分析模型则使分析结果与生物意义的对应关系下降;分析方法对2种原核生物和2种真核生物具有较好的统一性。【结论】通信纠错编码模型与蕴含纠错机制的生物序列编码特性可以较好地结合,这对将纠错编码理论与生物学研究相结合具有一定的指导意义。     

生物体内氨基酸与遗传密码关系研究

mRNA的核苷酸序列通过密码子决定了蛋白质的氨基酸序列 ,密码子的使用频率及其在mRNA二级结构中分布的差异 ,影响到氨基酸的相对含量及蛋白质的空间结构。密码子的使用频率及氨酰 -tRNA合成酶对tRNA的识别 ,影响到生物体内氨基酸的生物配比     

How old is the genetic code? Statistical geometry of tRNA provides an answer

The age of the molecular organization of life as expressed in the genetic code can be estimated from experimental data. Comparative sequence analysis of transfer RNA by the method of statistical geometry in sequence space suggests that about one-third of the present transfer RNA sequence divergence was present at the urkingdom level about the time when archaebacteria separated from eubacteria. It is concluded that the genetic code is not older than, but almost as old as our planet. While this result may not be unexpected, it was not clear until now that interpretable data exist that permit inferences about such early stages of life as the establishment of the genetic code.     

Suppressor selectrion for amino acid replacements expected on the basis of the genetic code

In studies with A protein mutants of the tryptophan synthetase of Escherichia coli, missense supressors have been used to select for codon changes and corresponding amino acid replacements that are normally unobservable. The technique has permitted the detection of additional amino acid replacements expected on the basis of the genetic code.     

一种改进的多种群量子遗传算法

针对常规量子遗传算法(Quantum genetic algorithm,QGA)在求解连续函数优化问题时容易陷入局部极值,提出了一种改进的多种群量子遗传算法(Improved multi-population quantum genetic algorithm,IMPQGA).该算法将初始化种群划分成N个子种群,每个子种群按不同的量子旋转门策略更新,然后相互交换子种群最优个体,同时在算法进化中引入一种新的量子旋转门,随进化代数增加动态地调整染色体个体进化方向,使算法及时跳出局部最优,避免早熟收敛.仿真结果表明,该算法相比常规量子遗传算法和多种群遗传算法(Multi-population quantum genetic algorithm,MPQGA)具有更好的优化性能.     

一种改进的遗传算法及其收敛性分析

为了克服基本遗传算法只考虑种内竞争的缺陷,提出了基于种间竞争的基本遗传算法的改进算法,并用Markov链分析了遗传算法的收敛性问题,证明了改进的遗传算法收敛到全局最优解的概率为1.通过考核实例计算,发现改进后的算法具有更强的鲁棒性.     

Reading a neural code

Traditional approaches to neural coding characterize the encoding of known stimuli in average neural responses. Organisms face nearly the opposite task--extracting information about an unknown time-dependent stimulus from short segments of a spike train. Here the neural code was characterized from the point of view of the organism, culminating in algorithms for real-time stimulus estimation based on a single example of the spike train. These methods were applied to an identified movement-sensitive neuron in the fly visual system. Such decoding experiments determined the effective noise level and fault tolerance of neural computation, and the structure of the decoding algorithms suggested a simple model for real-time analog signal processing with spiking neurons.