SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination

The Escherichia coli gene recQ was identified as a RecF recombination pathway gene. The gene SGS1, encoding the only RecQ-like DNA helicase in Saccharomyces cerevisiae, was identified by mutations that suppress the top3 slow-growth phenotype. Relatively little is known about the function of Sgs1p because single mutations in SGS1 do not generally cause strong phenotypes. Mutations in genes encoding RecQ-like DNA helicases such as the Bloom and Werner syndrome genes, BLM and WRN, have been suggested to cause increased genome instability. But the exact DNA metabolic defect that might underlie such genome instability has remained unclear. To better understand the cellular role of the RecQ-like DNA helicases, sgs1 mutations were analyzed for their effect on genome rearrangements. Mutations in SGS1 increased the rate of accumulating gross chromosomal rearrangements (GCRs), including translocations and deletions containing extended regions of imperfect homology at their breakpoints. sgs1 mutations also increased the rate of recombination between DNA sequences that had 91% sequence homology. Epistasis analysis showed that Sgs1p is redundant with DNA mismatch repair (MMR) for suppressing GCRs and for suppressing recombination between divergent DNA sequences. This suggests that defects in the suppression of rearrangements involving divergent, repeated sequences may underlie the genome instability seen in BLM and WRN patients and in cancer cases associated with defects in these genes.     

Single-nucleotide polymorphisms in the public domain: how useful are they?

There is a concerted effort by a number of public and private groups to identify a large set of human single-nucleotide polymorphisms (SNPs). As of March 2001, 2.84 million SNPs have been deposited in the public database, dbSNP, at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/). The 2.84 million SNPs can be grouped into 1.65 million non-redundant SNPs. As part of the International SNP Map Working Group, we recently published a high-density SNP map of the human genome consisting of 1.42 million SNPs (ref. 3). In addition, numerous SNPs are maintained in proprietary databases. Our survey of more than 1,200 SNPs indicates that more than 80% of TSC and Washington University candidate SNPs are polymorphic and that approximately 50% of the candidate SNPs from these two sources are common SNPs (with minor allele frequency of > or =20%) in any given population.     

Cool Indonesian throughflow as a consequence of restricted surface layer flow

Approximately 10 million m3 x s(-1) of water flow from the Pacific Ocean into the Indian Ocean through the Indonesian seas. Within the Makassar Strait, the primary pathway of the flow, the Indonesian throughflow is far cooler than estimated earlier, as pointed out recently on the basis of ocean current and temperature measurements. Here we analyse ocean current and stratification data along with satellite-derived wind measurements, and find that during the boreal winter monsoon, the wind drives buoyant, low-salinity Java Sea surface water into the southern Makassar Strait, creating a northward pressure gradient in the surface layer of the strait. This surface layer 'freshwater plug' inhibits the warm surface water from the Pacific Ocean from flowing southward into the Indian Ocean, leading to a cooler Indian Ocean sea surface, which in turn may weaken the Asian monsoon. The summer wind reversal eliminates the obstructing pressure gradient, by transferring more-saline Banda Sea surface water into the southern Makassar Strait. The coupling of the southeast Asian freshwater budget to the Pacific and Indian Ocean surface temperatures by the proposed mechanism may represent an important negative feedback within the climate system.     

The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria

Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.     

Language-tree divergence times support the Anatolian theory of Indo-European origin

Languages, like genes, provide vital clues about human history. The origin of the Indo-European language family is "the most intensively studied, yet still most recalcitrant, problem of historical linguistics". Numerous genetic studies of Indo-European origins have also produced inconclusive results. Here we analyse linguistic data using computational methods derived from evolutionary biology. We test two theories of Indo-European origin: the 'Kurgan expansion' and the 'Anatolian farming' hypotheses. The Kurgan theory centres on possible archaeological evidence for an expansion into Europe and the Near East by Kurgan horsemen beginning in the sixth millennium BP. In contrast, the Anatolian theory claims that Indo-European languages expanded with the spread of agriculture from Anatolia around 8,000-9,500 years bp. In striking agreement with the Anatolian hypothesis, our analysis of a matrix of 87 languages with 2,449 lexical items produced an estimated age range for the initial Indo-European divergence of between 7,800 and 9,800 years bp. These results were robust to changes in coding procedures, calibration points, rooting of the trees and priors in the bayesian analysis.     

知识经济时代我国人力资源管理现状及其对策

知识经济时代,人才的竞争就是人才制度的竞争,即人力资源开发和管理水平的竞争。文章分析了我国人力资源管理的现状、成因及对策,指出必须借鉴发达国家的经验和做法,强化我国人力资源开发和管理的战略性地位,并总结和探索适合我国国情的人力资源开发和管理的机制、方法和技术。     

稳步推进科学发展

由科技部牵头,教育部、中科院、国家自然科学基金委等有关部门共同发起,委托国家自然科学基金委具体组织了数学、物理学、化学、天文学、地学、生物学、力学、心理学、基础医学、基础农学、材料科学、能源科学、资源环境科学、空间科学、信息科学、工程科学、海洋科学、管理科学18个学科的调研活动.调研活动围绕相关学科的地位与作用、国际发展态势、我国的研究现状和学科发展前沿等.根据我国科学研究的基础,从国家发展科学研究的重大需求出发,遵循学科自身发展规律,就"十五"至2010年期间,我国主要基础学科的发展目标、方向、前沿和优先领域以及政策保障措施等方面提出了积极的建议.本次调研活动的成果汇编成<中国基础学科发展报告>,本文系该<报告>的总论.     

Novel dominant mutations in Saccharomyces cerevisiae MSH6

Inherited mutations in the mismatch repair (MMR) genes MSH2 and MLH1 are found in most hereditary nonpolyposis colon cancer (HNPCC) patients studied. Eukaryotic MMR uses two partially redundant mispair-recognition complexes, Msh2p-Msh6p and Msh2p-Msh3p (ref.2) Inactivation of MSH2 causes high rates of accumulation of both base-substitution and frameshift mutations. Mutations in MSH6 or MSH3 cause partial defects in MMR, with inactivation of MSH6 resulting in high rates of base-substitution mutations and low rates of frameshift mutations; inactivation of MSH3 results in low rates of frameshift mutations. These different mutator phenotypes provide an explanation for the observation that MSH2 mutations are common in HNPCC families, whereas mutations in MSH3 and MSH6 are rare. We have identified novel missense mutations in Saccharomyces cerevisiae MSH6 that appear to inactivate both Msh2p-Msh6p- and Msh2p-Msh3p-dependent MMR. Our work suggests that such mutations may underlie some cases of inherited cancer susceptibility similar to those caused by MSH2 mutations.