Author Report for: Deng ZNo contact information in database for Deng Z
Tan Y, Pan J, Deng Z, Chen T, Xia J, Liu Z, Zou C, Qin B Ref: Front Immunol, 14:1161960, 2023 : PubMed ESTHER: Tan_2023_Front.Immunol_14_1161960 PubMedSearch: Tan 2023 Front.Immunol 14 1161960 PubMedID: 37033945 Abstract BACKGROUND: Although lipid metabolism has been proven to play a key role in the development of cancer, its significance in uveal melanoma (UM) has not yet been elucidated in the available literature. METHODS: To identify the expression patterns of lipid metabolism in 80 UM patients from the TCGA database, 47 genes involved in lipid metabolism were analyzed. Consensus clustering revealed two distinct molecular groups. ESTIMATE, TIMER, and ssGSEA analyses were done to identify the differences between the two subgroups in tumor microenvironment (TME) and immune state. Using Cox regression and Lasso regression analysis, a risk model based on differentially expressed genes (DEGs) was developed. To validate the expression of monoacylglycerol lipase (MGLL) and immune infiltration in diverse malignancies, a pan-cancer cohort from the UCSC database was utilized. Next, a single-cell sequencing analysis on UM patients from the GEO data was used to characterize the lipid metabolism in TME and the role of MGLL in UM. Finally, in vitro investigations were utilized to study the involvement of MGLL in UM. RESULTS: Two molecular subgroups of UM patients have considerably varied survival rates. The majority of DEGs between the two subgroups were associated with immune-related pathways. Low immune scores, high tumor purity, a low number of immune infiltrating cells, and a comparatively low immunological state were associated with a more favorable prognosis. An examination of GO and KEGG data demonstrated that the risk model based on genes involved with lipid metabolism can accurately predict survival in patients with UM. It has been demonstrated that MGLL, a crucial gene in this paradigm, promotes the proliferation, invasion, and migration of UM cells. In addition, we discovered that MGLL is strongly expressed in macrophages, specifically M2 macrophages, which may play a function in the M2 polarization of macrophages and M2 macrophage activation in cancer cells. CONCLUSION: This study demonstrates that the risk model based on lipid metabolism may be useful for predicting the prognosis of patients with UM. By promoting macrophage M2 polarization, MGLL contributes to the evolution of malignancy in UM, suggesting that it may be a therapeutic target for UM. Title: Enzymatic Synthesis of beta-Sitosterol Laurate by Candida rugosa Lipase AY30 in the Water/AOT/Isooctane Reverse Micelle Chen S, Li J, Fu Z, Wei G, Li H, Zhang B, Zheng L, Deng Z Ref: Appl Biochem Biotechnol, :, 2020 : PubMed ESTHER: Chen_2020_Appl.Biochem.Biotechnol__ PubMedSearch: Chen 2020 Appl.Biochem.Biotechnol PubMedID: 32388606 Abstract Phytosterols are regarded as compounds able to reduce total and low-density lipoprotein cholesterol in the blood, and their esterified derivatives could help to improve the effectiveness of this function. In the present study, the water/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/isooctane reverse micelle (RM) system was set up as a reaction medium for Candida rugosa lipase AY30 (CRL AY30) to synthesize beta-sitosterol laurate (beta-SLE). The product was identified by TLC, FT-IR, and HPLC-APCI-QqQ-MS/MS and quantified by HPLC. Through stepwise optimization, it was found that CRL AY30 had the highest activity in the water/AOT/isooctane RM system where 50 mM PBS with a pH of 7.5 was adopted as water core to carry CRL AY30, and the proportion of [CRL AY30] (mg/mL), [water] (mM), and [AOT] (mM) was set in 3:375:25, respectively, in isooctane. After screened with single-factor experiments, the esterification reaction conditions in the CRL AY30-water/AOT/isooctane RM system were further optimized by the response surface method as follows: the mole ratio of beta-sitosterol to lauric acid of 1:3.5 (25 mM beta-sitosterol), the enzyme load of 18% (w/w total reactants), the reaction temperature of 47 degrees C, and the reaction time of 48 h. As a result, the maximum esterification rate was up to 88.12 +/- 0.79%. Title: Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007 Liu R, Fang F, An Z, Huang R, Wang Y, Sun X, Fu S, Fu A, Deng Z, Liu T Ref: J Ind Microbiol Biotechnol, 47:275, 2020 : PubMed ESTHER: Liu_2020_J.Ind.Microbiol.Biotechnol_47_275 PubMedSearch: Liu 2020 J.Ind.Microbiol.Biotechnol 47 275 PubMedID: 31853778 Gene_locus related to this paper: 9actn-a0a6i4pr03 Abstract Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of Actinomadura sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs in silico to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming Actinomadura sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future. Title: A novel streptonigrin type alkaloid from the Streptomyces flocculus CGMCC 4.1223 mutant stnA/Q2 Wang X, Xu F, Huang T, Deng Z, Lin S Ref: Nat Prod Res, :1, 2020 : PubMed ESTHER: Wang_2020_Nat.Prod.Res__3 PubMedSearch: Wang 2020 Nat.Prod.Res 3 PubMedID: 33280413 Gene_locus related to this paper: 9actn-l7pij2 Abstract Streptonigrin (STN) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activities. Previously, the biosynthetic gene cluster of STN was identified in Streptomyces flocculus CGMCC 4.1223, revealing an alpha/beta-hydrolase (StnA) and a methyltransferase (StnQ2). In this work, a double mutant delta stnA/Q2 was constructed by genetic manipulation and produced a novel derivative of STN, named as streptonigramide. Structure of streptonigramide was established by spectroscopic analyses. Its biosynthetic pathway has been proposed as well. Title: Structural Insights into the Substrate Specificity of Acyltransferases from Salinomycin Polyketide Synthase Zhang F, Shi T, Ji H, Ali I, Huang S, Deng Z, Min Q, Bai L, Zhao Y, Zheng J Ref: Biochemistry, 58:2978, 2019 : PubMed ESTHER: Zhang_2019_Biochemistry_58_2978 PubMedSearch: Zhang 2019 Biochemistry 58 2978 PubMedID: 31199122 Abstract Salinomycin with antibacterial and anticoccidial activities is a commercial polyether polyketide widely used in animal husbandry as a food additive. Malonyl-CoA (MCoA), methylmalonyl-CoA (MMCoA), and ethylmalonyl-CoA (EMCoA) are used as extension units in its biosynthesis. To understand how the salinomycin modular polyketide synthase (PKS) strictly discriminates among these extension units, the acyltransferase (AT) domains selecting MCoA, MMCoA, and EMCoA were structurally characterized. Molecular dynamics simulations of the AT structures helped to reveal the key interactions involved in enzyme-substrate recognitions, which enabled the engineering of AT mutants with switched specificity. The catalytic efficiencies ( kcat/ Km) of these AT mutants are comparable with those of the wild-type AT domains. These results set the stage for engineering the AT substrate specificity of modular PKSs. Title: Food up-take and reproduction performance of Daphnia magna under the exposure of Bisphenols Liu Y, Yan Z, Zhang L, Deng Z, Yuan J, Zhang S, Chen J, Guo R Ref: Ecotoxicology & Environmental Safety, 170:47, 2018 : PubMed ESTHER: Liu_2018_Ecotoxicol.Environ.Saf_170_47 PubMedSearch: Liu 2018 Ecotoxicol.Environ.Saf 170 47 PubMedID: 30522006 Abstract Because the application of Bisphenol A (BPA) was restricted, many substitutes, such as Bisphenol F (BPF) and Bisphenol S (BPS), were developed as BPA substitutes. Therefore, environmental impacts of BPA and its substitutes on aquatic organisms should be concerned, especially their combined toxicity. In this study, the impacts of BPA, BPF, BPS and their mixture on the feeding behavior, reproduction and physiological function of daphnids were synthetically evaluated, involving the duration and mode of exposure. In short-term exposure tests, feeding rates of D. magna decreased after exposure to BPA, BPF, BPS and their mixture, while the inhibition reversed into stimulation in the recovery period. It may benefit from overcompensation of D. magna. In long-term exposure tests, the inhibition effect on the reproduction and growth of the exposed D. magna was difficult to recover, and only some experimental groups have a certain recovery. In conclusion, environmental risk of BPA, BPF, BPS and their mixture on the behavior of D. magna increased with prolonged exposure time. Moreover, relative activities of trypsin, amylase (AMS), acetylcholinesterase (AChE), carbonic anhydrase (CA), glutathione peroxidase (GPx) and super oxidase dimutase (SOD) of the exposed daphnids decreased in most treatment groups, indicating the disorder of digestive, nervous and antioxidative system of D. magna. Interestingly, inhibition of enzymes activities decreased with the increase of the exposure time, which implied the tolerance may be occurred. Title: Maternal obesity aggravates the abnormality of porcine placenta by increasing N(6)-methyladenosine Song T, Lu J, Deng Z, Xu T, Yang Y, Wei H, Li S, Jiang S, Peng J Ref: Int J Obes (Lond), 42:1812, 2018 : PubMed ESTHER: Song_2018_Int.J.Obes.(Lond)_42_1812 PubMedSearch: Song 2018 Int.J.Obes.(Lond) 42 1812 PubMedID: 29795472 Abstract BACKGROUND: The growing prevalence of overweight or obese pregnancies shows an increasing risk for aberrant fetal growth and postnatal complications. Maternal obesity is associated with low birth weight (LBW) of piglets. However, the development of LBW from maternal obesity is not well understood. OBJECTIVE: This study attempts to investigate the novel RNA modification N6-methyladenosine (m(6)A) in the placenta tissues by using sows with high backfat thickness as a model for obese pregnancy. SUBJECTS/METHODS: Forty four placentas from eight sows (backfat thickness >/=21 mm) were divided into four groups by piglet weight, with group1 being LBW group (<1.0 kg), group2 (1.0-1.4 kg), group3 (1.4-1.6 kg), and group4 (>1.6 kg) as the comparative groups of normal birth weight. QPCR was used to measure the mRNA levels of the genes and western blot was used to test the content of proteins. At the same time, LC-MS/MS method was built to test the content of m(6)A modification in the placental RNA, and finally MeRIP-QPCR technology was employed to check the specific m(6)A modification in the key genes. RESULTS: Compared with the comparative groups, the expression levels of PPARgamma, VEGFA, ABHD5, and GPR120 in both mRNA and protein decreased noticeably in the LBW group. It was also observed that the density of the H&E stained vessels became attenuated in LBW group. Importantly, for the first time, the increased m(6)A levels were found in LBW placentas. Lower protein level of FTO (the key demethylase of m(6)A) was observed in LBW placentas, whereas no difference was found among the four groups in the expression levels of METTL3, the main methyltransferase of m(6)A. By using MeRIP-QPCR technology, the m(6)A modification in PPARgamma, VEGFA, ABHD5, and GPR120, as well as FTO, was considerably enhanced in the placentas from LBW group. CONCLUSION: We infer that in maternity obesity, the higher m(6)A modification displayed in the genes related to placental development, lipid metabolism and angiogenesis may result in the down regulation of these genes, which could be associated with m(6)A demethylase FTO. Title: Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease Liao S, Deng H, Huang S, Yang J, Wang S, Yin B, Zheng T, Zhang D, Liu J and Deng Z <2 more author(s)> Liao S, Deng H, Huang S, Yang J, Wang S, Yin B, Zheng T, Zhang D, Liu J, Gao G, Ma J, Deng Z (- 2) Ref: Bioorganic & Medicinal Chemistry Lett, 25:1541, 2015 : PubMed ESTHER: Liao_2015_Bioorg.Med.Chem.Lett_25_1541 PubMedSearch: Liao 2015 Bioorg.Med.Chem.Lett 25 1541 PubMedID: 25724825 Abstract A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BCHE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (Abeta) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8nM, potent inhibition of self-induced Abeta1-42 aggregation with inhibition ratio of 33.8% at 25muM. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD. Title: Design of hyperthermophilic lipase chimeras by key motif-directed recombination Zhou X, Gao L, Yang G, Liu D, Bai A, Li B, Deng Z, Feng Y Ref: Chembiochem, 16:455, 2015 : PubMed ESTHER: Zhou_2015_Chembiochem_16_455 PubMedSearch: Zhou 2015 Chembiochem 16 455 PubMedID: 25530200 Abstract Recombination of diverse natural evolved domains within a superfamily offers greater opportunity for enzyme function leaps. How to recombine protein modules from distant parents with less disruption in cross-interfaces is a challenging issue. Here, we identified the existence of a key motif, the sequence VVSVN(D)YR, within a structural motif psi loop in the alpha/beta-hydrolase fold superfamily, by using a MEME server and the PROMOTIF program. To obtain thermostable lipase-like enzymes, two chimeras were engineered at the key motif regions through recombination of domains from a mesophilic lipase and a hyperthermophilic esterase/peptidase with amino acid identity less than 21 %. The chimeras retained the desirable substrate preference of their mesophilic parent and exhibited more than 100-fold increased thermostability at 50 degrees C. Through site-directed mutation, we further improved activity of the chimera by 4.6-fold. The recombination strategy presented here enables the creation of novel catalysts. Title: Operon for biosynthesis of lipstatin, the Beta-lactone inhibitor of human pancreatic lipase Bai T, Zhang D, Lin S, Long Q, Wang Y, Ou H, Kang Q, Deng Z, Liu W, Tao M Ref: Applied Environmental Microbiology, 80:7473, 2014 : PubMed ESTHER: Bai_2014_Appl.Environ.Microbiol_80_7473 PubMedSearch: Bai 2014 Appl.Environ.Microbiol 80 7473 PubMedID: 25239907 Inhibitor(s) related to this paper: Lipstatin Abstract Lipstatin, isolated from Streptomyces toxytricini as a potent and selective inhibitor of human pancreatic lipase, is a precursor for tetrahydrolipstatin (also known as orlistat, Xenical, and Alli), the only FDA-approved antiobesity medication for long-term use. Lipstatin features a 2-hexyl-3,5-dihydroxy-7,10-hexadecadienoic-beta-lactone structure with an N-formyl-l-leucine group attached as an ester to the 5-hydroxy group. It has been suggested that the alpha-branched 3,5-dihydroxy fatty acid beta-lactone moiety of lipstatin in S. toxytricini is derived from Claisen condensation between two fatty acid substrates, which are derived from incomplete oxidative degradation of linoleic acid based on feeding experiments. In this study, we identified a six-gene operon (lst) that was essential for the biosynthesis of lipstatin by large-deletion, complementation, and single-gene knockout experiments. lstA, lstB, and lstC, which encode two beta-ketoacyl-acyl carrier protein synthase III homologues and an acyl coenzyme A (acyl-CoA) synthetase homologue, were indicated to be responsible for the generation of the alpha-branched 3,5-dihydroxy fatty acid backbone. Subsequently, the nonribosomal peptide synthetase (NRPS) gene lstE and the putative formyltransferase gene lstF were involved in decoration of the alpha-branched 3,5-dihydroxy fatty acid chain with an N-formylated leucine residue. Finally, the 3beta-hydroxysteroid dehydrogenase-homologous gene lstD might be responsible for the reduction of the beta-keto group of the biosynthetic intermediate, thereby facilitating the formation of the unique beta-lactone ring. Title: Characterization of streptonigrin biosynthesis reveals a cryptic carboxyl methylation and an unusual oxidative cleavage of a N-C bond Xu F, Kong D, He X, Zhang Z, Han M, Xie X, Wang P, Cheng H, Tao M and Lin S <2 more author(s)> Xu F, Kong D, He X, Zhang Z, Han M, Xie X, Wang P, Cheng H, Tao M, Zhang L, Deng Z, Lin S (- 2) Ref: Journal of the American Chemical Society, 135:1739, 2013 : PubMed ESTHER: Xu_2013_J.Am.Chem.Soc_135_1739 PubMedSearch: Xu 2013 J.Am.Chem.Soc 135 1739 PubMedID: 23301954 Gene_locus related to this paper: 9actn-l7pij2 Abstract Streptonigrin (STN, 1) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activity. Here, we reported the biosynthetic gene cluster of STN identified by genome scanning of a STN producer Streptomyces flocculus CGMCC4.1223. This cluster consists of 48 genes determined by a series of gene inactivations. On the basis of the structures of intermediates and shunt products accumulated from five specific gene inactivation mutants and feeding experiments, the biosynthetic pathway was proposed, and the sequence of tailoring steps was preliminarily determined. In this pathway, a cryptic methylation of lavendamycin was genetically and biochemically characterized to be catalyzed by a leucine carboxyl methyltransferase StnF2. A [2Fe-2S](2+) cluster-containing aromatic ring dioxygenase StnB1/B2 system was biochemically characterized to catalyze a regiospecific cleavage of the N-C8' bond of the indole ring of the methyl ester of lavendamycin. This work provides opportunities to illuminate the enzymology of novel reactions involved in this pathway and to create, using genetic and chemo-enzymatic methods, new streptonigrinoid analogues as potential therapeutic agents. Title: Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase Zhu J, Wu CF, Li X, Wu GS, Xie S, Hu QN, Deng Z, Zhu MX, Luo HR, Hong X Ref: Bioorganic & Medicinal Chemistry, 21:4218, 2013 : PubMed ESTHER: Zhu_2013_Bioorg.Med.Chem_21_4218 PubMedSearch: Zhu 2013 Bioorg.Med.Chem 21 4218 PubMedID: 23719283 Abstract A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BCHE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BCHE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BCHE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100muM of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face pi-pi stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09A) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BCHE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BCHE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BCHE, potentially useful to treat neurodegenerative diseases. Title: Complete genome sequence of Klebsiella pneumoniae subsp. pneumoniae HS11286, a multidrug-resistant strain isolated from human sputum Liu P, Li P, Jiang X, Bi D, Xie Y, Tai C, Deng Z, Rajakumar K, Ou HY Ref: Journal of Bacteriology, 194:1841, 2012 : PubMed ESTHER: Liu_2012_J.Bacteriol_194_1841 PubMedSearch: Liu 2012 J.Bacteriol 194 1841 PubMedID: 22408243 Gene_locus related to this paper: klep7-a6t9v6, klep7-menh, klep7-y1077, klepn-w8uta0 Abstract Klebsiella pneumoniae is an important pathogen commonly associated with opportunistic infections. Here we report the genome sequence of a strain, HS11286, isolated from human sputum in 2011 in Shanghai, China. It contains one chromosome (5.3 Mb), three multidrug resistance plasmids ( approximately 110 kb), including a carbapenemase producer, and three small plasmids ( approximately 3 kb). Title: Genomic and transcriptomic insights into the thermo-regulated biosynthesis of validamycin in Streptomyces hygroscopicus 5008 Wu H, Qu S, Lu C, Zheng H, Zhou X, Bai L, Deng Z Ref: BMC Genomics, 13:337, 2012 : PubMed ESTHER: Wu_2012_BMC.Genomics_13_337 PubMedSearch: Wu 2012 BMC.Genomics 13 337 PubMedID: 22827618 Gene_locus related to this paper: strhj-h2k4a5 Abstract BACKGROUND: Streptomyces hygroscopicus 5008 has been used for the production of the antifungal validamycin/jinggangmycin for more than 40 years. A high yield of validamycin is achieved by culturing the strain at 37 degreesC, rather than at 30 degreesC for normal growth and sporulation. The mechanism(s) of its thermo-regulated biosynthesis was largely unknown. RESULTS: The 10,383,684-bp genome of strain 5008 was completely sequenced and composed of a linear chromosome, a 164.57-kb linear plasmid, and a 73.28-kb circular plasmid. Compared with other Streptomyces genomes, the chromosome of strain 5008 has a smaller core region and shorter terminal inverted repeats, encodes more alpha/beta hydrolases, major facilitator superfamily transporters, and Mg2+/Mn2+-dependent regulatory phosphatases. Transcriptomic analysis revealed that the expression of 7.5% of coding sequences was increased at 37 degreesC, including biosynthetic genes for validamycin and other three secondary metabolites. At 37 degreesC, a glutamate dehydrogenase was transcriptionally up-regulated, and further proved its involvement in validamycin production by gene replacement. Moreover, efficient synthesis and utilization of intracellular glutamate were noticed in strain 5008 at 37 degreesC, revealing glutamate as the nitrogen source for validamycin biosynthesis. Furthermore, a SARP-family regulatory gene with enhanced transcription at 37 degreesC was identified and confirmed to be positively involved in the thermo-regulation of validamycin production by gene inactivation and transcriptional analysis. CONCLUSIONS: Strain 5008 seemed to have evolved with specific genomic components to facilitate the thermo-regulated validamycin biosynthesis. The data obtained here will facilitate future studies for validamycin yield improvement and industrial bioprocess optimization. Title: Complete genome sequence of the nitrogen-fixing and rhizosphere-associated bacterium Pseudomonas stutzeri strain DSM4166 Yu H, Yuan M, Lu W, Yang J, Dai S, Li Q, Yang Z, Dong J, Sun L and Lin M <8 more author(s)> Yu H, Yuan M, Lu W, Yang J, Dai S, Li Q, Yang Z, Dong J, Sun L, Deng Z, Zhang W, Chen M, Ping S, Han Y, Zhan Y, Yan Y, Jin Q, Lin M (- 8) Ref: Journal of Bacteriology, 193:3422, 2011 : PubMed ESTHER: Yu_2011_J.Bacteriol_193_3422 PubMedSearch: Yu 2011 J.Bacteriol 193 3422 PubMedID: 21515765 Gene_locus related to this paper: pseu5-a4vfn0, pseu5-a4vj02, pseu5-a4vrl9, pseut-f8h720, pseu5-a4vkl7, pseu5-a4vgd4, pseu5-a4vr33 Abstract We present here the analysis of the whole-genome sequence of Pseudomonas stutzeri strain DSM4166, a diazotrophic isolate from the rhizosphere of a Sorghum nutans cultivar. To our knowledge, this is the second genome to be sequenced for P. stutzeri. The availability and analysis of the genome provide insight into the evolution of the nitrogen fixation property and identification of rhizosphere competence traits required in interactions with host plants. Title: The genes coding for the conversion of carbazole to catechol are flanked by IS6100 elements in Sphingomonas sp. strain XLDN2-5 Gai Z, Wang X, Liu X, Tai C, Tang H, He X, Wu G, Deng Z, Xu P Ref: PLoS ONE, 5:e10018, 2010 : PubMed ESTHER: Gai_2010_PLoS.One_5_e10018 PubMedSearch: Gai 2010 PLoS.One 5 e10018 PubMedID: 20368802 Abstract BACKGROUND: Carbazole is a recalcitrant compound with a dioxin-like structure and possesses mutagenic and toxic activities. Bacteria respond to a xenobiotic by recruiting exogenous genes to establish a pathway to degrade the xenobiotic, which is necessary for their adaptation and survival. Usually, this process is mediated by mobile genetic elements such as plasmids, transposons, and insertion sequences. FINDINGS: The genes encoding the enzymes responsible for the degradation of carbazole to catechol via anthranilate were cloned, sequenced, and characterized from a carbazole-degrading Sphingomonas sp. strain XLDN2-5. The car gene cluster (carRAaBaBbCAc) and fdr gene were accompanied on both sides by two copies of IS6100 elements, and organized as IS6100::ISSsp1-ORF1-carRAaBaBbCAc-ORF8-IS6100-fdr-IS6100. Carbazole was converted by carbazole 1,9a-dioxygenase (CARDO, CarAaAcFdr), meta-cleavage enzyme (CarBaBb), and hydrolase (CarC) to anthranilate and 2-hydroxypenta-2,4-dienoate. The fdr gene encoded a novel ferredoxin reductase whose absence resulted in lower transformation activity of carbazole by CarAa and CarAc. The ant gene cluster (antRAcAdAbAa) which was involved in the conversion of anthranilate to catechol was also sandwiched between two IS6100 elements as IS6100-antRAcAdAbAa-IS6100. Anthranilate 1,2-dioxygenase (ANTDO) was composed of a reductase (AntAa), a ferredoxin (AntAb), and a two-subunit terminal oxygenase (AntAcAd). Reverse transcription-PCR results suggested that carAaBaBbCAc gene cluster, fdr, and antRAcAdAbAa gene cluster were induced when strain XLDN2-5 was exposed to carbazole. Expression of both CARDO and ANTDO in Escherichia coli required the presence of the natural reductases for full enzymatic activity. CONCLUSIONS/SIGNIFICANCE: We predict that IS6100 might play an important role in the establishment of carbazole-degrading pathway, which endows the host to adapt to novel compounds in the environment. The organization of the car and ant genes in strain XLDN2-5 was unique, which showed strong evolutionary trail of gene recruitment mediated by IS6100 and presented a remarkable example of rearrangements and pathway establishments. Title: Characterization of the polyoxin biosynthetic gene cluster from Streptomyces cacaoi and engineered production of polyoxin H Chen W, Huang T, He X, Meng Q, You D, Bai L, Li J, Wu M, Li R and Deng Z <4 more author(s)> Chen W, Huang T, He X, Meng Q, You D, Bai L, Li J, Wu M, Li R, Xie Z, Zhou H, Zhou X, Tan H, Deng Z (- 4) Ref: Journal of Biological Chemistry, 284:10627, 2009 : PubMed ESTHER: Chen_2009_J.Biol.Chem_284_10627 PubMedSearch: Chen 2009 J.Biol.Chem 284 10627 PubMedID: 19233844 Gene_locus related to this paper: strci-c1ic18 Abstract A gene cluster (pol) essential for the biosynthesis of polyoxin, a nucleoside antibiotic widely used for the control of phytopathogenic fungi, was cloned from Streptomyces cacaoi. A 46,066-bp region was sequenced, and 20 of 39 of the putative open reading frames were defined as necessary for polyoxin biosynthesis as evidenced by its production in a heterologous host, Streptomyces lividans TK24. The role of PolO and PolA in polyoxin synthesis was demonstrated by in vivo experiments, and their functions were unambiguously characterized as O-carbamoyltransferase and UMP-enolpyruvyltransferase, respectively, by in vitro experiments, which enabled the production of a modified compound differing slightly from that proposed earlier. These studies should provide a solid foundation for the elucidation of the molecular mechanisms for polyoxin biosynthesis, and set the stage for combinatorial biosynthesis using genes encoding different pathways for nucleoside antibiotics. Title: polR, a pathway-specific transcriptional regulatory gene, positively controls polyoxin biosynthesis in Streptomyces cacaoi subsp. asoensis Li R, Xie Z, Tian Y, Yang H, Chen W, You D, Liu G, Deng Z, Tan H Ref: Microbiology, 155:1819, 2009 : PubMed ESTHER: Li_2009_Microbiology_155_1819 PubMedSearch: Li 2009 Microbiology 155 1819 PubMedID: 19383687 Gene_locus related to this paper: strci-c1ic18 Abstract The polyoxin (POL) biosynthetic gene cluster (pol) was recently cloned from Streptomyces cacaoi subsp. asoensis. A 3.3 kb DNA fragment carrying an obvious open reading frame (polR), whose deduced product shows sequence similarity to SanG of Streptomyces ansochromogenes and PimR of Streptomyces natalensis, was revealed within the pol gene cluster. Disruption of polR abolished POL production, which could be complemented by the integration of a single copy of polR into the chromosome of the non-producing mutant. The introduction of an extra copy of polR in the wild-type strain resulted in increased production of POLs. The transcription start point (tsp) of polR was determined by S1 mapping. Reverse transcriptase PCR experiments showed that PolR is required for the transcription of 18 structural genes in the pol gene cluster. Furthermore, we showed that polC and polB, the respective first genes of two putative operons (polC-polQ2 and polA-polB) consisting of 16 and 2 of these 18 genes, have similar promoter structures. Gel retardation assays indicated that PolR has specific DNA-binding activity for the promoter regions of polC and polB. Our data suggest that PolR acts in a positive manner to regulate POL production by activating the transcription of at least two putative operons in the pol gene cluster. Title: Complete genomic characterization of a pathogenic A.II strain of Francisella tularensis subspecies tularensis Beckstrom-Sternberg SM, Auerbach RK, Godbole S, Pearson JV, Beckstrom-Sternberg JS, Deng Z, Munk C, Kubota K, Zhou Y and Keim PS <11 more author(s)> Beckstrom-Sternberg SM, Auerbach RK, Godbole S, Pearson JV, Beckstrom-Sternberg JS, Deng Z, Munk C, Kubota K, Zhou Y, Bruce D, Noronha J, Scheuermann RH, Wang A, Wei X, Wang J, Hao J, Wagner DM, Brettin TS, Brown N, Gilna P, Keim PS (- 11) Ref: PLoS ONE, 2:e947, 2007 : PubMed ESTHER: Beckstrom-Sternberg_2007_PLoS.ONE_2_E947 PubMedSearch: Beckstrom-Sternberg 2007 PLoS.ONE 2 E947 PubMedID: 17895988 Gene_locus related to this paper: fratt-q5ngu5 Abstract Francisella tularensis is the causative agent of tularemia, which is a highly lethal disease from nature and potentially from a biological weapon. This species contains four recognized subspecies including the North American endemic F. tularensis subsp. tularensis (type A), whose genetic diversity is correlated with its geographic distribution including a major population subdivision referred to as A.I and A.II. The biological significance of the A.I - A.II genetic differentiation is unknown, though there are suggestive ecological and epidemiological correlations. In order to understand the differentiation at the genomic level, we have determined the complete sequence of an A.II strain (WY96-3418) and compared it to the genome of Schu S4 from the A.I population. We find that this A.II genome is 1,898,476 bp in size with 1,820 genes, 1,303 of which code for proteins. While extensive genomic variation exists between "WY96" and Schu S4, there is only one whole gene difference. This one gene difference is a hypothetical protein of unknown function. In contrast, there are numerous SNPs (3,367), small indels (1,015), IS element differences (7) and large chromosomal rearrangements (31), including both inversions and translocations. The rearrangement borders are frequently associated with IS elements, which would facilitate intragenomic recombination events. The pathogenicity island duplicated regions (DR1 and DR2) are essentially identical in WY96 but vary relative to Schu S4 at 60 nucleotide positions. Other potential virulence-associated genes (231) varied at 559 nucleotide positions, including 357 non-synonymous changes. Molecular clock estimates for the divergence time between A.I and A.II genomes for different chromosomal regions ranged from 866 to 2131 years before present. This paper is the first complete genomic characterization of a member of the A.II clade of Francisella tularensis subsp. tularensis. Title: Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A Bai L, Li L, Xu H, Minagawa K, Yu Y, Zhang Y, Zhou X, Floss HG, Mahmud T, Deng Z Ref: Chemical Biology, 13:387, 2006 : PubMed ESTHER: Bai_2006_Chem.Biol_13_387 PubMedSearch: Bai 2006 Chem.Biol 13 387 PubMedID: 16632251 Gene_locus related to this paper: strhy-q1l2j3 Abstract A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VAL-A) biosynthesis revealed 16 structural genes, 2 regulatory genes, 5 genes related transport, transposition/integration or tellurium resistance; another 4 genes had no obvious identity. The VAL-A biosynthetic pathway was proposed, with assignment of the required genetic functions confined to the sequenced region. A cluster of eight reassembled genes was found to support VAL-A synthesis in a heterologous host, S. lividans 1326. In vivo inactivation of the putative glycosyltransferase gene (valG) abolished the final attachment of glucose for VAL production and resulted in accumulation of the VAL-A precursor, validoxylamine, while the normal production of VAL-A could be restored by complementation with valG. The role of valG in the glycosylation of validoxylamine to VAL-A was demonstrated in vitro by enzymatic assay. Title: Gene and alternative splicing annotation with AIR Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV and Sutton G <5 more author(s)> Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G (- 5) Ref: Genome Res, 15:54, 2005 : PubMed ESTHER: Florea_2005_Genome.Res_15_54 PubMedSearch: Florea 2005 Genome.Res 15 54 PubMedID: 15632090 Gene_locus related to this paper: mouse-Ppgb, rat-d3zaw4, rat-dpp9, rat-d3zhq1, rat-d3zxw8, rat-d4a4w4, rat-d4a7w1, rat-d4a071, rat-Tex30, ratno-1plip, ratno-3plip, ratno-ABH15, ratno-balip, ratno-Ces1d, ratno-d3zxq0, ratno-est8, ratno-pbcxe, ratno-phebest, ratno-q6mg55, ratno-thyro, rat-m0rc77, rat-d3zba8, rat-f1lvg7, rat-b5den3, rat-d4a1b6, rat-d3zmg4 Abstract Designing effective and accurate tools for identifying the functional and structural elements in a genome remains at the frontier of genome annotation owing to incompleteness and inaccuracy of the data, limitations in the computational models, and shifting paradigms in genomics, such as alternative splicing. We present a methodology for the automated annotation of genes and their alternatively spliced mRNA transcripts based on existing cDNA and protein sequence evidence from the same species or projected from a related species using syntenic mapping information. At the core of the method is the splice graph, a compact representation of a gene, its exons, introns, and alternatively spliced isoforms. The putative transcripts are enumerated from the graph and assigned confidence scores based on the strength of sequence evidence, and a subset of the high-scoring candidates are selected and promoted into the annotation. The method is highly selective, eliminating the unlikely candidates while retaining 98% of the high-quality mRNA evidence in well-formed transcripts, and produces annotation that is measurably more accurate than some evidence-based gene sets. The process is fast, accurate, and fully automated, and combines the traditionally distinct gene annotation and alternative splicing detection processes in a comprehensive and systematic way, thus considerably aiding in the ensuing manual curation efforts. Title: Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex Chen S, Huang X, Zhou X, Bai L, He J, Jeong KJ, Lee SY, Deng Z Ref: Chemical Biology, 10:1065, 2003 : PubMed ESTHER: Chen_2003_Chem.Biol_10_1065 PubMedSearch: Chen 2003 Chem.Biol 10 1065 PubMedID: 14652074 Gene_locus related to this paper: 9acto-q6w5p8, strgr-pabt Abstract The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively. Title: A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin Sun Y, Zhou X, Dong H, Tu G, Wang M, Wang B, Deng Z Ref: Chemical Biology, 10:431, 2003 : PubMed ESTHER: Sun_2003_Chem.Biol_10_431 PubMedSearch: Sun 2003 Chem.Biol 10 431 PubMedID: 12770825 Gene_locus related to this paper: strna-NANE Abstract The PKS genes for biosynthesis of the polyether nanchangmycin are organized to encode two sets of proteins (six and seven ORFs, respectively), but are separated by independent ORFs that encode an epimerase, epoxidase, and epoxide hydrolase, and, notably, an independent ACP. One of the PKS modules lacks a corresponding ACP. We propose that the process of oxidative cyclization to form the polyether structure occurs when the polyketide chain is still anchored on the independent ACP before release. 4-O-methyl-L-rhodinose biosynthesis and its transglycosylation involve four putative genes, and regulation of nanchangmycin biosynthesis seems to involve activation as well as repression. In-frame deletion of a KR6 domain generated the nanchangmycin aglycone with loss of 4-O-methyl-L-rhodinose and antibacterial activity, in agreement with the assignments of the PKS domains catalyzing specific biosynthetic steps. Title: A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG and Stephenson LD <169 more author(s)> Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG, Nadeau J, Salzberg SL, Holt RA, Kodira CD, Lu F, Chen L, Deng Z, Evangelista CC, Gan W, Heiman TJ, Li J, Li Z, Merkulov GV, Milshina NV, Naik AK, Qi R, Shue BC, Wang A, Wang J, Wang X, Yan X, Ye J, Yooseph S, Zhao Q, Zheng L, Zhu SC, Biddick K, Bolanos R, Delcher AL, Dew IM, Fasulo D, Flanigan MJ, Huson DH, Kravitz SA, Miller JR, Mobarry CM, Reinert K, Remington KA, Zhang Q, Zheng XH, Nusskern DR, Lai Z, Lei Y, Zhong W, Yao A, Guan P, Ji RR, Gu Z, Wang ZY, Zhong F, Xiao C, Chiang CC, Yandell M, Wortman JR, Amanatides PG, Hladun SL, Pratts EC, Johnson JE, Dodson KL, Woodford KJ, Evans CA, Gropman B, Rusch DB, Venter E, Wang M, Smith TJ, Houck JT, Tompkins DE, Haynes C, Jacob D, Chin SH, Allen DR, Dahlke CE, Sanders R, Li K, Liu X, Levitsky AA, Majoros WH, Chen Q, Xia AC, Lopez JR, Donnelly MT, Newman MH, Glodek A, Kraft CL, Nodell M, Ali F, An HJ, Baldwin-Pitts D, Beeson KY, Cai S, Carnes M, Carver A, Caulk PM, Center A, Chen YH, Cheng ML, Coyne MD, Crowder M, Danaher S, Davenport LB, Desilets R, Dietz SM, Doup L, Dullaghan P, Ferriera S, Fosler CR, Gire HC, Gluecksmann A, Gocayne JD, Gray J, Hart B, Haynes J, Hoover J, Howland T, Ibegwam C, Jalali M, Johns D, Kline L, Ma DS, MacCawley S, Magoon A, Mann F, May D, McIntosh TC, Mehta S, Moy L, Moy MC, Murphy BJ, Murphy SD, Nelson KA, Nuri Z, Parker KA, Prudhomme AC, Puri VN, Qureshi H, Raley JC, Reardon MS, Regier MA, Rogers YH, Romblad DL, Schutz J, Scott JL, Scott R, Sitter CD, Smallwood M, Sprague AC, Stewart E, Strong RV, Suh E, Sylvester K, Thomas R, Tint NN, Tsonis C, Wang G, Williams MS, Williams SM, Windsor SM, Wolfe K, Wu MM, Zaveri J, Chaturvedi K, Gabrielian AE, Ke Z, Sun J, Subramanian G, Venter JC, Pfannkoch CM, Barnstead M, Stephenson LD (- 169) Ref: Science, 296:1661, 2002 : PubMed ESTHER: Mural_2002_Science_296_1661 PubMedSearch: Mural 2002 Science 296 1661 PubMedID: 12040188 Gene_locus related to this paper: mouse-ABH15, mouse-Ces3b, mouse-Ces4a, mouse-dpp4, mouse-FAP, mouse-Lipg, mouse-Q8C1A9, mouse-rbbp9, mouse-SERHL, mouse-SPG21, mouse-w4vsp6 Abstract The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart. Title: The sequence of the human genome Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264) Ref: Science, 291:1304, 2001 : PubMed ESTHER: Venter_2001_Science_291_1304 PubMedSearch: Venter 2001 Science 291 1304 PubMedID: 11181995 Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21 Abstract A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. Title: The genome sequence of Drosophila melanogaster Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA and Venter JC <185 more author(s)> Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, George RA, Lewis SE, Richards S, Ashburner M, Henderson SN, Sutton GG, Wortman JR, Yandell MD, Zhang Q, Chen LX, Brandon RC, Rogers YH, Blazej RG, Champe M, Pfeiffer BD, Wan KH, Doyle C, Baxter EG, Helt G, Nelson CR, Gabor GL, Abril JF, Agbayani A, An HJ, Andrews-Pfannkoch C, Baldwin D, Ballew RM, Basu A, Baxendale J, Bayraktaroglu L, Beasley EM, Beeson KY, Benos PV, Berman BP, Bhandari D, Bolshakov S, Borkova D, Botchan MR, Bouck J, Brokstein P, Brottier P, Burtis KC, Busam DA, Butler H, Cadieu E, Center A, Chandra I, Cherry JM, Cawley S, Dahlke C, Davenport LB, Davies P, de Pablos B, Delcher A, Deng Z, Mays AD, Dew I, Dietz SM, Dodson K, Doup LE, Downes M, Dugan-Rocha S, Dunkov BC, Dunn P, Durbin KJ, Evangelista CC, Ferraz C, Ferriera S, Fleischmann W, Fosler C, Gabrielian AE, Garg NS, Gelbart WM, Glasser K, Glodek A, Gong F, Gorrell JH, Gu Z, Guan P, Harris M, Harris NL, Harvey D, Heiman TJ, Hernandez JR, Houck J, Hostin D, Houston KA, Howland TJ, Wei MH, Ibegwam C, Jalali M, Kalush F, Karpen GH, Ke Z, Kennison JA, Ketchum KA, Kimmel BE, Kodira CD, Kraft C, Kravitz S, Kulp D, Lai Z, Lasko P, Lei Y, Levitsky AA, Li J, Li Z, Liang Y, Lin X, Liu X, Mattei B, McIntosh TC, McLeod MP, McPherson D, Merkulov G, Milshina NV, Mobarry C, Morris J, Moshrefi A, Mount SM, Moy M, Murphy B, Murphy L, Muzny DM, Nelson DL, Nelson DR, Nelson KA, Nixon K, Nusskern DR, Pacleb JM, Palazzolo M, Pittman GS, Pan S, Pollard J, Puri V, Reese MG, Reinert K, Remington K, Saunders RD, Scheeler F, Shen H, Shue BC, Siden-Kiamos I, Simpson M, Skupski MP, Smith T, Spier E, Spradling AC, Stapleton M, Strong R, Sun E, Svirskas R, Tector C, Turner R, Venter E, Wang AH, Wang X, Wang ZY, Wassarman DA, Weinstock GM, Weissenbach J, Williams SM, WoodageT, Worley KC, Wu D, Yang S, Yao QA, Ye J, Yeh RF, Zaveri JS, Zhan M, Zhang G, Zhao Q, Zheng L, Zheng XH, Zhong FN, Zhong W, Zhou X, Zhu S, Zhu X, Smith HO, Gibbs RA, Myers EW, Rubin GM, Venter JC (- 185) Ref: Science, 287:2185, 2000 : PubMed ESTHER: Adams_2000_Science_287_2185 PubMedSearch: Adams 2000 Science 287 2185 PubMedID: 10731132 Gene_locus related to this paper: drome-1vite, drome-2vite, drome-3vite, drome-a1z6g9, drome-abhd2, drome-ACHE, drome-b6idz4, drome-BEM46, drome-CG5707, drome-CG5704, drome-CG1309, drome-CG1882, drome-CG1986, drome-CG2059, drome-CG2493, drome-CG2528, drome-CG2772, drome-CG3160, drome-CG3344, drome-CG3523, drome-CG3524, drome-CG3734, drome-CG3739, drome-CG3744, drome-CG3841, drome-CG4267, drome-CG4382, drome-CG4390, drome-CG4572, drome-CG4582, drome-CG4851, drome-CG4979, drome-CG5068, drome-CG5162, drome-CG5355, drome-CG5377, drome-CG5397, drome-CG5412, drome-CG5665, drome-CG5932, drome-CG5966, drome-CG6018, drome-CG6113, drome-CG6271, drome-CG6283, drome-CG6295, drome-CG6296, drome-CG6414, drome-CG6431, drome-CG6472, drome-CG6567, drome-CG6675, drome-CG6753, drome-CG6847, drome-CG7329, drome-CG7367, drome-CG7529, drome-CG7632, drome-CG8058, drome-CG8093, drome-CG8233, drome-CG8424, drome-CG8425, drome-CG9059, drome-CG9186, drome-CG9287, drome-CG9289, drome-CG9542, drome-CG9858, drome-CG9953, drome-CG9966, drome-CG10116, drome-CG10163, drome-CG10175, drome-CG10339, drome-CG10357, drome-CG10982, drome-CG11034, drome-CG11055, drome-CG11309, drome-CG11319, drome-CG11406, drome-CG11598, drome-CG11600, drome-CG11608, drome-CG11626, drome-CG11935, drome-CG12108, drome-CG12869, drome-CG13282, drome-CG13562, drome-CG13772, drome-CG14034, drome-nlg3, drome-CG14717, drome-CG15101, drome-CG15102, drome-CG15106, drome-CG15111, drome-CG15820, drome-CG15821, drome-CG15879, drome-CG17097, drome-CG17099, drome-CG17101, drome-CG17191, drome-CG17192, drome-CG17292, drome-CG18258, drome-CG18284, drome-CG18301, drome-CG18302, drome-CG18493, drome-CG18530, drome-CG18641, drome-CG18815, drome-CG31089, drome-CG31091, drome-CG32333, drome-CG32483, drome-CG33174, drome-dnlg1, drome-este4, drome-este6, drome-GH02384, drome-GH02439, drome-glita, drome-KRAKEN, drome-lip1, drome-LIP2, drome-lip3, drome-MESK2, drome-nrtac, drome-OME, drome-q7k274, drome-Q9VJN0, drome-Q8IP31, drome-q9vux3 Abstract The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity. | |||||||
|
