Similar numbers but different repertoires of olfactory receptor genes in humans and chimpanzees

Animals recognize their external world through the detection of tens of thousands of chemical odorants. Olfactory receptor (OR) genes encode proteins for detecting odorant molecules and form the largest multigene family in mammals. It is known that humans have fewer OR genes and a higher fraction of OR pseudogenes than mice or dogs. To investigate whether these features are human specific or common to all higher primates, we identified nearly complete sets of OR genes from the chimpanzee and macaque genomes and compared them with the human OR genes. In contrast to previous studies, here we show that the number of OR genes ( approximately 810) and the fraction of pseudogenes (51%) in chimpanzees are very similar to those in humans, though macaques have considerably fewer OR genes. The pseudogenization rates and the numbers of genes affected by positive selection are also similar between humans and chimpanzees. Moreover, the most recent common ancestor between humans and chimpanzees had a larger number of functional OR genes (>500) and a lower fraction of pseudogenes (41%) than its descendents, suggesting that the OR gene repertoires are in a phase of deterioration in both lineages. Interestingly, despite the close evolutionary relationship between the 2 species, approximately 25% of their functional gene repertoires are species specific due to massive gene losses. These findings suggest that the tempo of evolution of OR genes is similar between humans and chimpanzees, but the OR gene repertoires are quite different between them. This difference might be responsible for the species-specific ability of odor perception.     

GeneLoc: exon-based integration of human genome maps

MOTIVATION:Despite the numerous available whole-genome mapping resources, no comprehensive, integrated map of the human genome yet exists. RESULTS: GeneLoc, software adjunct to GeneCards and UDB, integrates gene lists by comparing genomic coordinates at the exon level and assigns unique and meaningful identifiers to each gene.     

Selection of target sites for mobile DNA integration in the human genome

DNA sequences from retroviruses, retrotransposons, DNA transposons, and parvoviruses can all become integrated into the human genome. Accumulation of such sequences accounts for at least 40% of our genome today. These integrating elements are also of interest as gene-delivery vectors for human gene therapy. Here we present a comprehensive bioinformatic analysis of integration targeting by HIV, MLV, ASLV, SFV, L1, SB, and AAV. We used a mathematical method which allowed annotation of each base pair in the human genome for its likelihood of hosting an integration event by each type of element, taking advantage of more than 200 types of genomic annotation. This bioinformatic resource documents a wealth of new associations between genomic features and integration targeting. The study also revealed that the length of genomic intervals analyzed strongly affected the conclusions drawn--thus, answering the question "What genomic features affect integration?" requires carefully specifying the length scale of interest.     

Similar replicon properties of higher plant cells with different S periods and genome sizes

Root meristematic cells of nine unrelated diploid higher plants with genome sizes that differ 82-fold and with S periods that differ 4-fold have similar replicon sizes and single replication fork rates that average 22 μm and 8 μm/h respectively. The average replicon size of 22 μm is near the 18 μm obtained by extrapolation of measurements, taken from DNA fiber autoradiograms, to zero pulse time with [³H]thymidine. The data suggest that the duration of S is determined by the minimal number of replicon families that function sequentially during DNA replication.     

LINEs, SINEs and processed pseudogenes: parasitic strategies for genome modeling

Two major classes of retrotransposons have invaded eukaryotic genomes: the LTR retrotransposons closely resembling the proviral integrated form of infectious retroviruses, and the non-LTR retrotransposons including the widespread, autonomous LINE elements. Here, we review the modeling effects of the latter class of elements, which are the most active in humans, and whose enzymatic machinery is subverted to generate a large series of "secondary" retroelements. These include the processed pseudogenes, naturally present in all eukaryotic genomes possessing non-LTR retroelements, and the very successful SINE elements such as the human Alu sequences which have evolved refined parasitic strategies to efficiently bypass the original "protectionist" cis-preference of LINEs for their own retrotransposition.     

Similar but different: ligand-induced activation of the insulin and epidermal growth factor receptor families

The insulin and epidermal growth factor receptor families are among the most intensively studied proteins in biology. They are closely related members of the receptor tyrosine kinase superfamily and deregulated signaling by members of either receptor family has been implicated in the progression of a variety of cancers. These receptors have thus emerged as validated therapeutic targets for the development of anti-tumour agents. Recent studies have revealed detail of the ligand-binding sites in the insulin receptor family, as well as detail of conformational change upon ligand binding in the epidermal growth factor receptor family. Taken together, these findings and further data relating to kinase activation highlight the fact that while the receptor families share common structural elements, the structural detail of their functioning is remarkably different.     

Similar taxonomic richness but different communities of ectomycorrhizas in native forests and non-native plantation forests

This investigation sought to examine if there was a difference between the ectomycorrhizal (ECM) communities in plots of native oak and introduced Scots pine and Sitka spruce forest. The ECM communities in four plots of each forest type were described, from five soil cores collected in each plot, by morphotyping, internal transcribed spacer (ITS)-restriction fragment length polymorphism matching of mycorrhizas and sporocarps and ITS sequencing. Fifty-one distinct taxa were distinguished; 25 were identified to species level, 11 to genus and 15 remained unidentified. Seventy-one ECM species were recorded as sporocarps from the forest plots; most (43 species) were found in the Sitka spruce plots. The below-ground ECM communities of the different forest types did not differ significantly with respect to species richness of taxa on roots, but differed in species composition. Multivariate analysis produced a clear separation of the communities of the different forest types using below-ground data, but the above-ground sporocarp data did not separate the forest types. Moreover, results of a Mantel test found no relationship between the above- and below-ground similarity matrices. The oak plots had the most distinctive ECM community, with Laccaria amethystina and Elaphomyces granulatus being frequent. The Sitka spruce plots showed the lowest intra-forest type similarity and were often dominated by "nursery type" ectomycorrhizas. There was only 10% similarity between the above- and below-ground ECM species in these plots, different colonisation methods of ectomycorrhizal taxa and insufficient below-ground sampling being possible reasons for this disparity. Our results indicate that plantations of non-native Sitka spruce can support similar levels of ECM diversity as native forests.     

Similar structures but different mechanisms: Prediction of FABPs-membrane interaction by electrostatic calculation

The role of fatty acid binding proteins as intracellular fatty acid transporters may require their direct interaction with membranes. In this way different mechanisms have been previously characterized through experimental studies suggesting different models for FABPs-membrane association, although the process in which the molecule adsorbs to the membrane remains to be elucidated. To estimate the importance of the electrostatic energy in the FABP-membrane interaction, we computationally modeled the interaction of different FABPs with both anionic and neutral membranes. Free Electrostatic Energy of Binding (dE), was computed using Finite Difference Poisson Boltzmann Equation (FDPB) method as implemented in APBS (Adaptive Poisson Boltzmann Solver). Based on the computational analysis, it is found that recruitment to membranes is facilitated by non-specific electrostatic interactions. Also energetic analysis can quantitatively differentiate among the mechanisms of membrane association proposed and determinate the most energetically favorable configuration for the membrane-associated states of different FABPs. This type of calculations could provide a starting point for further computational or experimental analysis.     

Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase

The development of new methods for gene addition to mammalian genomes is necessary to overcome the limitations of conventional genetic engineering strategies. Although a variety of DNA-modifying enzymes have been used to directly catalyze the integration of plasmid DNA into mammalian genomes, there is still an unmet need for enzymes that target a single specific chromosomal site. We recently engineered zinc-finger recombinase (ZFR) fusion proteins that integrate plasmid DNA into a synthetic target site in the human genome with exceptional specificity. In this study, we present a two-step method for utilizing these enzymes in any cell type at randomly-distributed target site locations. The piggyBac transposase was used to insert recombinase target sites throughout the genomes of human and mouse cell lines. The ZFR efficiently and specifically integrated a transfected plasmid into these genomic target sites and into multiple transposons within a single cell. Plasmid integration was dependent on recombinase activity and the presence of recombinase target sites. This work demonstrates the potential for broad applicability of the ZFR technology in genome engineering, synthetic biology and gene therapy.     

Organization and integration sites in the human genome of endogenous retroviral sequences belonging to HERV-E family

The present paper reports the characterization of HERV-E endogenous retroviral sequences in the human genome by using three complementary approaches. Firstly, we identified genomic clones containing HERV-E by BLAST screening of human DNA databases by using the entire sequence of a characterized HERV-E clone (M10976) as a query. The genomic structure and integration sites of the HERV-E elements were characterized. Secondly, new integration sites of HERV-E elements were revealed by a retroviral LTR-arbitrary primer-PCR (RELAP-PCR) technique. BLAST analysis of the PCR products identified a subgroup that shows low identity (75%) to the original clone M10976 and slightly higher identity (80%) to a closely related HERV-E (Ac. n. K02166). Finally, we performed FISH mapping, which revealed sites of integration of HERV-E not previously identified at the cytogenetic level. A preliminary analysis of genes mapping in the same bands as HERV-E integration sites was performed: several loci relevant to physiological and/or pathological processes were detected. Our findings may provide clues to identify HERV-E integration sites adjacent to genes with important biological roles.     

Alu中剪接位点的研究

对Alu剪接位点双碱基的类型、分布进行了分析,发现非标准剪接（不满足GT-AG规则）占很大优势。而且非标准剪接的分布频率会随不同的染色体而变化,在Alu剪接较多的11、12、17号染色体上分布最多。通过对Alu及其剪接住点碱基关联的计算分析,说明在Alu中剪接位点双碱基的这种异常使用主要是由Alu中二联体的关联压力造成的,从而表明这种重复序列对生命活动的多样化起着重要作用。     

Similar composition but differential stability of mineral retained organic matter across four classes of clay minerals

Adsorption of dissolved organic compounds onto mineral surfaces is increasingly recognized as a significant, if not dominant, carbon stabilisation mechanism in many soils. By utilising carbon-13 enriched dissolved organic carbon (DOC) source materials in a repeated leaching-sorption-incubation study, we show here that the biochemical composition of mineral-retained organic matter (OM) is similar across four different classes of clay minerals but the quantity and stability of this OM is both a function of source material and clay mineralogy. Three to eight times as much carbon was retained on a mass basis when the same amount of DOC derived from eucalyptus versus wheat litter was applied, and the retained wheat-derived OM was up to 2.4 times more degradable than that of the eucalyptus source. For both litter types, carbon retention across the clay types was not significantly different; whereas, the stability of the retained OM was different but depended on which litter extract had been applied. The wheat-derived DOC was more stable when retained by allophane and oxides than by illite and smectite. Solid-state ¹³C NMR spectroscopic results indicated that despite large compositional differences in both source litter and resultant DOC, the composition of the mineral-retained OM was similar across clay classes with lignin-derived aromatic and carboxylic compounds dominating. Differences in the amount of carbon retained were related to differences in the proportions of aromatic, phenolic and carboxylic C in the DOC produced from the two litter sources. Differences in the stability across the clay classes were correlated with the abundance of metals and short-range ordered minerals. These results suggest that whenever reactive mineral surfaces and metals are present in a soil, a similar form of relatively unaltered litter derived OM can be adsorbed but that the longer term stability of sorbed OM, and thus in situ composition, will be a function of the mineralogy (reactivity) of the specific minerals involved in the binding process.     

Retropositional parasitism of SINEs on LINEs: identification of SINEs and LINEs in elasmobranchs.

Some previously unidentified short interspersed repetitive elements (SINEs) and long interspersed repetitive element (LINEs) were isolated from various higher elasmobranchs (sharks, skates, and rays) and characterized. These SINEs, members of the HE1 SINE family, were tRNA-derived and were widespread in higher elasmobranches. The 3'-tail region of this SINE family was strongly conserved among elasmobranchs. The LINEs, members of the HER1 LINE family, encoded an amino acid sequence similar to that encoded by the chicken CR1 LINE family, and they contained a strongly conserved 3'-tail region in the 3' untranslated region. This tail region of the HER1 LINE family was almost identical to that of the HE1 SINE family. Thus, the HE1 SINE family and the HER1 LINE family provide a clear example of a pair of SINEs and LINEs that share the same tail region. Conservation of the secondary structures of the tail regions, as well as of the nucleotide sequences, between the HE1 SINE family and HER1 LINE family during evolution suggests that SINEs utilize the enzymatic machinery for retroposition of LINEs through the recognition of higher-order structures of the conserved 3'-tail region. A discussion is presented of the parasitism of SINEs on LINEs during the evolution of these retroposons.     

DNA聚合酶在维持基因组稳定性中的多重功能及其相关疾病

遗传物质的稳定传递是生命繁衍的根本。基因组DNA的精确复制和分配是遗传物质传递的基础,也是细胞周期两大最核心的生物学事件。DNA聚合酶作为催化合成DNA双链的酶,是复制过程中最重要的因子之一。尽管对这类酶的研究已有将近60年的历史,但依然是生命科学基础研究的前沿之一。真核生物中已知的DNA聚合酶有十几种,它们不仅参与正常基因组DNA合成过程,也参与DNA损伤情况下多种修复过程。如此众多的具有不同特性的DNA聚合酶在细胞内是如何分工与合作的,在正常细胞传代与环境胁迫等情况下维护基因组稳定性中的关键作用及其分子机制又是什么。更有意思的是,最近的肿瘤细胞比较基因组数据表明,多种DNA聚合酶基因突变与某些肿瘤和遗传疾病相关,从而为这些疾病致病机理研究与诊治提供了新的思路和方法。对上述DNA聚合酶相关核心问题的最新研究进展进行了综述。     

Vitamin E and genome stability

Free radicals and reactive oxygen species (ROS) which are generated continuously cause mutagenic alterations resulting in cancer, aging and abnormalities in the nervous system. Accumulating evidence indicates that Vitamin E, the most potent lipid peroxyl radical scavenger, may reduce free radical induced chromosomal damages through inhibition of free radical formation, and activation of endonuclease that can be triggered by intracellular oxidative stress, and by increasing the rate of removal of damaged DNA. Although some studies suggest a potential usefulness of Vitamin E in the prevention of mutagenic effects caused by genotoxic free radicals, other studies report no effects. Thus the data are not conclusive enough to be used as a basis to change the current recommended dietary allowances (RDA). Future research should address molecular mechanisms underlying the protective effects of Vitamin E and develop appropriate biologically relevant biomarkers of DNA damage to further help in determining the dietary levels of Vitamin E needed to protect the genetic pool from internally and externally induced DNA damages.     

Chromatin remodeling and genome stability

A report on the 12th Tenovus Scotland Symposium 'Stability and Regulation of Genes and Genomes', Glasgow UK, 6-7 April 2006.