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Nackley AG Shabalina SA Tchivileva IE Satterfield K Korchynskyi O Makarov SS Maixner W Diatchenko L 《Science (New York, N.Y.)》2006,314(5807):1930-1933
Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous position, code for differences in COMT enzymatic activity and are associated with pain sensitivity. Haplotypes divergent in synonymous changes exhibited the largest difference in COMT enzymatic activity, due to a reduced amount of translated protein. The major COMT haplotypes varied with respect to messenger RNA local stem-loop structures, such that the most stable structure was associated with the lowest protein levels and enzymatic activity. Site-directed mutagenesis that eliminated the stable structure restored the amount of translated protein. These data highlight the functional significance of synonymous variations and suggest the importance of haplotypes over single-nucleotide polymorphisms for analysis of genetic variations. 相似文献
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Holmes EC Lipman DJ Zamarin D Yewdell JW 《Science (New York, N.Y.)》2006,313(5793):1573; author reply 1573
Obenauer et al. (Research Articles, 17 March 2006, p. 1576) reported that the influenza A virus PB1-F2 gene is evolving under strong positive selection, as documented by an extremely high ratio of the number of nonsynonymous nucleotide substitutions to the number of synonymous substitutions (dN/dS). However, we show that this observation is likely to be an artifact related to the location of PB1-F2 in the +1 reading frame of the PB1 gene. 相似文献
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《农业科学学报》2016,(12)
The mitogen-activated protein kinase(MAPK), a key signal transduction component in the MAPK cascade pathway, regulates a variety of physiological activities in eukaryotes. However, little is known of the role MAPK plays in phytopathogenic fungi. In this research, we cloned the MAPK gene STK1 from the northern corn leaf blight pathogen Setosphaeria turcica and found that the gene shared high homology with the high osmolality glycerol(HOG) MAPK gene HOG1 of Saccharomyces cerevisiae. In addition, gene knockout technology was employed to investigate the function of STK1. Gene knockout mutants(KOs) were found to have altered hyphae morphology and no conidiogenesis, though they did show similar radial growth rate compared to the wild-type strain(WT). Furthermore, microscope observations indicated that STK1 KOs did not form normal appressoria at 48 h post-inoculation on a hydrophobic surface. STK1 KOs had reduced virulence, a significantly altered Helminthosporium turcicum(HT)-toxin composition, and diminished pathogenicity on the leaves of susceptible inbred corn OH43. Mycelium morphology appeared to be significantly swollen and the radial growth rates of STK1 KOs declined in comparison with WT under high osmotic stress. These results suggested that STK1 affects the hyphae development, conidiogenesis, and pathogenicity of S. turcica by regulating appressorium development and HT-toxin biosynthesis. Moreover, the gene appears to be involved in the hypertonic stress response in S. turcica. 相似文献
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钙依赖蛋白激酶(CDPK或CPK)在植物生长和发育、逆境信号刺激及其对病原物的防御反应过程中发挥着非常重要的作用。本研究利用梨树全基因组数据,采用生物信息学的方法,在全基因组水平上对梨树CDPK基因家族进行系谱进化关系、基因结构、共线性关系及表达情况等分析。结果表明,梨树基因组中共存在31个CDPK基因,命名为PbCDPK1~PbCDPK31。系谱分析结果表明,这些CDPK基因归属于4个亚家族。共线性分析检测到12对CDKP基因间存在显著的共线性关系,其中10对由最近一次发生的全基因组复制事件形成。非同义/同义置换率的比率(dN/dS)说明CDPK基因在功能上进化得非常保守。荧光定量PCR结果发现,5个梨树CDPK基因对干旱逆境有响应。试验结果可为进一步开展梨树CDPK基因家族的功能鉴定和分子进化机制的研究提供参考。 相似文献
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《东北农业大学学报(英文版)》2020,(2)
Salmonella gallinarum has shown multiple drug resistance (MDR),especially high level fluoroquinolone (FQ) resistance in recent years.To determine whether the active efflux system was responsible for high-level FQ resistance,this research studied AcrAB efflux pump in Salmonella gallinarum on molecular level.The resistant strains were induced by standard strain C79-13 with ciprofloxacin in vitro.With carbonylcyanide-p-chlorophenyl hydrazone (CCCP) as an energy inhibitor,efflux inhibition test initially showed the potential impact of efflux pump on drug resistance.Sequence analysis of acrA gene indicated that gene mutation of AcrAB efflux pump was not definitely associated with MDR and drug resistance level of Salmonella gallinarum.Detected by competitive RT-PCR,the mRNA expression of acrA and acrB genes in the resistant strains significantly increased (p0.01) compared with that of the control strain C79-13.The mRNA expression level of acrB gene (increased from 1.6-to 2.9-folds) was consistent with that of acrA gene (increased from 1.6-to 2.8-folds),which increased with the drug resistance level.However,gene mutation of acrA gene showed no correlation with its mRNA expression level,indicating that gene mutation did not affect the expression of AcrAB pump itself.The results suggested that the overexpression rather than the gene mutation of AcrAB efflux pump was an important factor causing the high level drug resistance of Salmonella gallinarum. 相似文献
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螯虾次目功能基因密码子偏好性研究 总被引：1，自引：0，他引：1
以螯虾次目功能基因组中的208个蛋白质编码基因序列为数据来源,应用CodonW 14软件对螯虾次目功能基因中密码子组成、同义密码子使用频率、密码子3个位置的G+C含量、有效密码子数等进行分析。结果显示,螯虾次目密码子第三位的G+C含量明显高于第一/二位,表现出对以G或C碱基结尾的密码子的偏好性使用,并确定了9个螯虾次目最优密码子。上述研究结果为今后螯虾次目新基因的发现、功能基因表达调控研究、蛋白质结构和功能预测、以及与其他虾类的比较基因组学研究、螯虾分子标记育种等提供了理论基础。 相似文献
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为了初步探究蕙兰磷脂酰乙醇胺结合蛋白(phosphatidyl ethanolamine-binding proteins, PEBP)基因的特征与功能,以蕙兰花蕾期叶片为材料,利用反转录PCR(RT-PCR)结合cDNA末端快速扩增(RACE)技术克隆基因,使用在线生物信息学工具进行蛋白结构与功能预测,通过R语言和3个在线软件(CodonW、CHIPS和CUSP)分析该基因的密码子偏好性。结果表明,克隆得到的蕙兰PEBP基因包含531 bp长度的开放阅读框(ORF),对应编码氨基酸176个。该基因命名为CfPEBP(登录号MT795710)。生物信息学分析表明,CfPEBP分子式为C882H1366N254O260S5,分子量为19 848.39 u;等电点为 6.42;具有15个磷酸化位点。CfPEBP蛋白无信号肽结构域,具有PEBP功能域。进化树分析结果表明,CfPEBP蛋白与春兰FT进化距离最近,同源性为100%。分析显示,CfPEBP的密码子偏好性表现较弱;依据同义密码子相对使用度(RSCU)分析较强偏性密码子有GGC、AGA、AGU、AAG、CCA、CUC(RSCU≥2.00)。18个物种PEBP基因RSCU值分析表明,蕙兰HQ164434、文心兰KJ909968、文心兰EU583502、石斛MF063061、香蕉KF853468、牵牛AB154823的密码偏好性较强,均有25个以上RSCU值>1. 00的密码子。PEBP家族基因对于GGC、AGG、AGA、AGC、AGU、UGC、GAG、AAG、UAC、GCC、CCA、CUC的偏好性超过其他密码子。CfPEBP基因在蕙兰盛花期叶中相对表达量最高,花蕾期花蕾和盛花期花葶中表达量次之,其他组织几乎不表达。本研究为蕙兰PEBP家族基因功能的进一步研究提供了基础。 相似文献
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甘南牦牛H-FABP基因CDS区多态性及生物信息学分析 总被引：1，自引：0，他引：1
应用PCR产物混合样本DNA池法检测甘南牦牛心脏型脂肪酸结合蛋白(H-FABP)基因CDS区多态性,并应用生物信息学方法分析甘南牦牛H-FABP蛋白质特性.结果表明:甘南牦牛H-FABP基因CDS区序列与九龙牦牛相同,而与普通牛对比在第3外显子存在*76G>A的同义突变;甘南牦牛H-FABP氨基酸序列没有明显的疏水性区域,也未形成跨膜螺旋区及信号肽,推测其主要在细胞质中发挥生物学作用;甘南牦牛H-FABP基因编码产物二级结构是以α-螺旋和β-折叠为主的mixed型;氨基酸序列与普通牛、山羊、马、人、小鼠、大鼠、鸡、草雀及绿鸭9个物种间同源性较高,与其实际亲缘关系远近一致. 相似文献
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Hong D Gupta R Ancliff P Atzberger A Brown J Soneji S Green J Colman S Piacibello W Buckle V Tsuzuki S Greaves M Enver T 《Science (New York, N.Y.)》2008,319(5861):336-339
Understanding cancer pathogenesis requires knowledge of not only the specific contributory genetic mutations but also the cellular framework in which they arise and function. Here we explore the clonal evolution of a form of childhood precursor-B cell acute lymphoblastic leukemia that is characterized by a chromosomal translocation generating a TEL-AML1 fusion gene. We identify a cell compartment in leukemic children that can propagate leukemia when transplanted in mice. By studying a monochorionic twin pair, one preleukemic and one with frank leukemia, we establish the lineal relationship between these "cancer-propagating" cells and the preleukemic cell in which the TEL-AML1 fusion first arises or has functional impact. Analysis of TEL-AML1-transduced cord blood cells suggests that TEL-AML1 functions as a first-hit mutation by endowing this preleukemic cell with altered self-renewal and survival properties. 相似文献
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二酰甘油酰基转移酶1（DGAT1）在乳脂合成过程中发挥重要作用,但水牛DGAT1基因第17外显子遗传多态性及其与产奶性状的关联性还不清楚。本文采用PCR-SSCP结合DNA测序方法对48头德宏水牛和93头产奶杂交水牛（F1: 摩拉水牛×德宏水牛）的第17外显子进行了多态性检测并结合乳成分数据进行了关联分析。在水牛DGAT1基因第17外显子发现1个SNP位点,即c.1350C＞G,其为同义替换。该SNP位点在德宏乳用和非乳用水牛中群体遗传组成相近,且不同基因型个体间的乳糖率、乳脂率及乳蛋白率无显著差异（P>0.05）。表明该SNP对水牛乳糖率、乳脂率及乳蛋白率等无显著影响。序列比对显示,水牛、普通牛、瘤牛、山羊和绵羊DGAT1基因第17外显子间仅存在1个编码氨基酸差异,揭示其具有较高的保守性。 相似文献
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为探究关岭牛TBC1D7(TBC1 domain family,member 7)基因单核苷酸多态性(single nucleotide polymorphism sites,SNPs)对其生长性状的影响。以贵州关岭牛为试验对象,构建DNA混合池,采用PCR扩增后直接测序法对关岭牛TBC1D7基因进行SNPs检测,并对其进行生物信息学分析。结果显示:关岭牛TBC1D7基因蛋白质编码区(CDS)全长882 bp,编码氨基酸293个,形成了一种不稳定的可溶性蛋白。该蛋白中不存在跨膜区域且不存在信号肽,为非分泌蛋白。蛋白中存在6个潜在的N-糖基化位点,二级结构主要由α-螺旋和无规则卷曲构成;在关岭牛TBC1D7基因CDS区共发现了4个同义突变位点,分别为c.402T>C、c.414A>G、c.609C>T和c.648T>C。4个突变位点均导致关岭牛TBC1D7基因mRNA二级结构、自由能和基因频率发生变化。本实验筛查到关岭牛TBC1D7基因4个SNPs位点,表明关岭牛TBC1D7基因多态性丰富,为进一步研究TBC1D7基因变异和关岭牛生长发育性状的相关性提供理论基础。 相似文献
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[目的]利用生物信息学方法分析基因的功能,[方法]通过生物信息学数据库和因特网上的软件进行分析,对小麦液泡膜Na+/H+反转运蛋白基因TaNHX1的理化性质、结构与功能进行了预测。[结果]TaNHX1基因编码的蛋白是一种相对分子质量为59.7 kD、等电点pI为8.13的疏水性稳定蛋白,富含Leu、Phe、Lle、Gly、Ser、Val、Ala等氨基酸。TaNHX1基因编码的氨基酸序列内含有一段氨氯吡嗪咪的结合域的高度保守序列FF-YLLPI。同源性比较发现TaNHX1与AeNHX1、TiNHX1的亲缘关系很近,分别是99%和97%,推测他们可能为同源基因,具有相似的生物学功能。[结论]该研究为进一步探讨TaNHX1的生物学功能奠定了基础。 相似文献
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Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock 总被引：1，自引：0，他引：1
Lithium is commonly used to treat bipolar disorder, which is associated with altered circadian rhythm. Lithium is a potent inhibitor of glycogen synthase kinase 3 (GSK3), which regulates circadian rhythm in several organisms. In experiments with cultured cells, we show here that GSK3beta phosphorylates and stabilizes the orphan nuclear receptor Rev-erbalpha, a negative component of the circadian clock. Lithium treatment of cells leads to rapid proteasomal degradation of Rev-erbalpha and activation of clock gene Bmal1. A form of Rev-erbalpha that is insensitive to lithium interferes with the expression of circadian genes. Control of Rev-erbalpha protein stability is thus a critical component of the peripheral clock and a biological target of lithium therapy. 相似文献
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为了研究波形蛋白在介导猪繁殖与呼吸综合征病毒(PRRSV)感染细胞过程中的作用,利用RT-PCR方法从PRRSV非易感细胞系猪肾细胞系PK-15细胞中扩增目的基因,克隆入pET-28a(+)载体,转化大肠杆菌BL21(DE3)中进行诱导表达。表达的重组猪波形蛋白经SDS-PAGE和Western blot鉴定和纯化后免疫新西兰大白兔制备多克隆抗体。利用病毒抑制试验检测重组猪波形蛋白及多克隆抗体在PRRSV感染Marc-145细胞过程中的作用。结果表明,成功扩增猪波形蛋白基因并克隆入pET-28a载体,经诱导后得到高效表达,纯化后免疫兔子产生高价血清抗体(105)。病毒阻断结果表明,猪波形蛋白及多克隆抗体均能阻断PRRSV感染Marc-145细胞。这为以波形蛋白为基础的PRRSV受体阻断抑制剂的研究提供了实验依据。 相似文献