Structural properties and tractability results for linear synteny

The syntenic distance between two species is the minimum number of fusions, fissions, and translocations required to transform one genome into the other. The linear syntenic distance, a restricted form of this model, has been shown to be close to the syntenic distance. Both models are computationally difficult to compute and have resisted efficient approximation algorithms with non-trivial performance guarantees. In this paper, we prove that many useful properties of syntenic distance carry over to linear syntenic distance. We also give a reduction from the general linear synteny problem to the question of whether a given instance can be solved using the maximum possible number of translocations. Our main contribution is an algorithm exactly computing linear syntenic distance in nested instances of the problem. This is the first polynomial time algorithm exactly solving linear synteny for a non-trivial class of instances. It is based on a novel connection between the syntenic distance and a scheduling problem that has been studied in the operations research literature.     

What to Learn from a Comparative Genomic Sequence Analysis of <Emphasis Type="Italic">L</Emphasis>-Carnitine Dehydrogenase

Summary. In contrast to eukaryotic cells certain eubacterial strains have acquired the ability to utilize L-carnitine (R-(–)-3-hydroxy-4-(trimethylamino)butyrate) as sole source of energy, carbon and nitrogen. The first step of the L-carnitine degradation to glycine betaine is catalysed by L-carnitine dehydrogenase (L-CDH, EC 1.1.1.108) and results in the formation of the dehydrocarnitine. During the oxidation of L-carnitine a simultaneous conversion of the cofactor NAD⁺ to NADH takes place. This catabolic reaction has always been of keen interest, because it can be exploited for spectroscopic L-carnitine determination in biological fluids – a quantification method, which is developed in our lab – as well as L-carnitine production.Based on a cloned L-CDH sequence an expedition through the currently available prokaryotic genomic sequence space began to mine relevant information about bacterial L-carnitine metabolism hidden in the enormous amount of data stored in public sequence databases. Thus by means of homology-based and context-based protein function prediction is revealed that L-CDH exists in certain eubacterial genomes either as a protein of approximately 35 kDa or as a homologous fusion protein of approximately 54 kDa with an additional putative domain, which is predicted to possess a thioesterase activity. These two variants of the enzyme are found on one hand in the genome sequence of bacterial species, which were previously reported to decompose L-carnitine, and on the other hand in gram-positive bacteria, which were not known to express L-CDH. Furthermore we could not only discover that L-CDH is located in a conserved genetic entity, which genes are very likely involved in this L-carnitine catabolic pathway, but also pinpoint the exact genomic sequence position of several other enzymes, which play an essential role in the bacterial metabolism of L-carnitine precursors.     

Tuning single nucleotide discrimination in polymerase chain reactions (PCRs): synthesis of primer probes bearing polar 4'-C-modifications and their application in allele-specific PCR

There are many methods available for the detection of nucleotide variations in genetic material. Most of these methods are applied after amplification of the target genome sequence by the polymerase chain reaction (PCR). Many efforts are currently underway to develop techniques that can detect single nucleotide variations in genes either by means of, or without the need for, PCR. Allele-specific PCR (asPCR), which reports nucleotide variations based on either the presence or absence of a PCR-amplified DNA product, has the potential to combine target amplification and analysis in one single step. The principle of asPCR is based on the formation of matched or mismatched primer-target complexes by using allele-specific primer probes. PCR amplification by a DNA polymerase from matched 3'-primer termini proceeds, whereas a mismatch should obviate amplification. Given the recent advancements in real-time PCR, this technique should, in principle, allow single nucleotide variations to be detected online. However, this method is hampered by low selectivity, which necessitates tedious and costly manipulations. Recently, we reported that the selectivity of asPCR can be significantly increased through the employment of chemically modified primer probes. Here we report further significant advances in this area. We describe the synthesis of various primer probes that bear polar 4'-C-modified nucleotide residues at their 3' termini, and their evaluation in real-time asPCR. We found that primer probes bearing a 4'-C-methoxymethylene modification have superior properties in the discrimination of single nucleotide variations by PCR.     

~(13)C代谢通量分析

代谢通量分析(metabolic flux analysis,MFA)是通过确定代谢网络中代谢流分布来表征细胞代谢状态的强有力的工具。鉴于计量学代谢通量分析在处理复杂代谢网络时表现出的局限性,发展了以13C标记实验为基础的13C MFA。本文介绍了13C MFA的原理与方法,总结和评述了13C MFA在实验与数据分析方面的最新进展以及MFA在功能基因组研究中的重要地位,同时对代谢通量分析的发展前景进行了展望。     

斑马鱼胚胎发育的功能染色体组

随着人类和其他物种染色体组测序工作的完成 ,人类科学最大的任务就是阐明数以万计的基因的生物功能。人类和动物生命周期都从受精卵开始 ,然后一步一步地发育成具有多元组织和器官的生物体。在胚胎形成过程中 ,伴随着基因生成物的协同运作 ,基因按其固有的程序陆续显现出影响 ,从而决定并实现整个人体程序。如果使用适当的动物做模型的话 ,可以加速胚胎功能染色体组的研究。斑马鱼就是这项研究一个很好的模型。斑马鱼最大的优点就是产卵多、体外胚胎发育、体积小、容易养活 ,除此以外 ,很多的分子、细胞、胚胎和基因操作在斑马鱼身上都很容…     

21世纪医学主要进展的预测--以人类后基因组研究为主要特征的医学革命时代

21世纪将是生命科学取得革命性飞跃性进展的时代,同时也是医学上取得伟大进展的时代.这个时代是以功能基因组即后基因组时代为主要特征而发展的,作者从21世纪人类功能基因组将取得的进展;治疗着眼于基因水平;诊断学上的革命;基因治疗将取得的成功;未来医学将把保健、预防、治疗、康复视为整体加以安排;新型有效药物将大量涌现;中医药将取得现代化的发展;人体报废的组织及器官的修复和更替置换;老年人疾病的预防、治疗和寿命的延长以及其它有关问题等十个方面预测了21世纪医药学发展的方方面面,为未来医药学发展提供了轮廓,指明了方向.     

Comparative Genomic Analysis Reveals Intestinal Habitat Adaptation of Ligilactobacillus equi Rich in Prophage and Degrading Cellulase

Ligilactobacillus equi is common in the horse intestine, alleviates the infection of Salmonella, and regulates intestinal flora. Despite this, there have been no genomic studies on this species. Here, we provide the genomic basis for adaptation to the intestinal habitat of this species. We sequenced the genome of L. equi IMAU81196, compared this with published genome information from three strains in NCBI, and analyzed genome characteristics, phylogenetic relationships, and functional genes. The mean genome size of L. equi strains was 2.08 ± 0.09 Mbp, and the mean GC content was 39.17% ± 0.19%. The genome size of L. equi IMAU81196 was 1.95 Mbp, and the GC content was 39.48%. The phylogenetic tree for L. equi based on 1454 core genes showed that the independent branch of strain IMAU81196 was far from the other three strains. In terms of genomic characteristics, single-nucleotide polymorphism (SNP) sites, rapid annotation using subsystem technology (RAST), carbohydrate activity enzymes (CAZy), and predictions of prophage, we showed that strain L. equi JCM 10991^T and strain DSM 15833^T are not equivalent strains.It is worth mentioning thatthestrain of L. equi has numerous enzymes related to cellulose degradation, and each L. equi strain investigated contained at least one protophage. We speculate that this is the reason why these strains are adapted to the intestinal environment of horses. These results provide new research directions for the future.     

结构基因组学与X-射线晶体衍射的研究进展

介绍了X-射线结晶学研究方面的新进展,包括蛋白质基因的克隆和表达载体的选择、蛋白质表达、蛋白质纯化、纯化的蛋白质的质量控制、高通量蛋白质结晶、晶体的收获和储存、同步加速器线束数据收集、自动的晶体固定和观察以及衍射质量分析和数据收集。