Nature：一种软骨鱼的第一个基因组序列

象鲨(Callorhinchus milii)是澳大利亚南部和新西兰温带水域的一种本地软骨鱼，生活在200米到500米深处，在春季迁移到浅水中进食。

本期Nature发表了这种鱼的基因组序列。与其他脊椎动物基因组所做比较显示，它是所有已知脊椎动物（包括腔棘鱼）中演化最慢的基因组。

基因组分析表明，它有一个不同寻常的适应性免疫系统，缺少CD4受体和一些相关的细胞因子，这说明软骨鱼拥有一个原始的有颌类适应性免疫系统。其基因组中也没有编码分泌的钙结合性磷蛋白的基因，这与软骨鱼没有骨头的事实是一致的。

Nature doi:10.1038/nature12826

Elephant shark genome provides unique insights into gnathostome evolution

Byrappa Venkatesh，  Alison P. Lee，  Vydianathan Ravi，  Ashish K. Maurya，  Michelle M. Lian， Jeremy B. Swann，  Yuko Ohta，  Martin F. Flajnik，  Yoichi Sutoh，  Masanori Kasahara，  Shawn Hoon，  Vamshidhar Gangu，  Scott W. Roy，  Manuel Irimia，  Vladimir Korzh，  Igor Kondrychyn， Zhi Wei Lim，  Boon-Hui Tay，  Sumanty Tohari，  Kiat Whye Kong，  Shufen Ho，  Belen Lorente-Galdos，  Javier Quilez，  Tomas Marques-Bonet，  Brian J. Raney

The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates was accompanied by major morphological and physiological innovations， such as hinged jaws， paired fins and immunoglobulin-based adaptive immunity. Gnathostomes subsequently diverged into two groups， the cartilaginous fishes and the bony vertebrates. Here we report the whole-genome analysis of a cartilaginous fish， the elephant shark (Callorhinchus milii). We find that the C. milii genome is the slowest evolving of all known vertebrates， including the ‘living fossil’ coelacanth， and features extensive synteny conservation with tetrapod genomes， making it a good model for comparative analyses of gnathostome genomes. Our functional studies suggest that the lack of genes encoding secreted calcium-binding phosphoproteins in cartilaginous fishes explains the absence of bone in their endoskeleton. Furthermore， the adaptive immune system of cartilaginous fishes is unusual： it lacks the canonical CD4 co-receptor and most transcription factors， cytokines and cytokine receptors related to the CD4 lineage， despite the presence of polymorphic major histocompatibility complex class II molecules. It thus presents a new model for understanding the origin of adaptive immunity.

Nat Commun：飞蝗荣登最大动物基因组榜首，支招摆脱蝗灾防控困扰

来自中国科学院动物研究所、深圳华大基因研究院等单位的科研人员成功破译了迄今为止最大的动物基因组–飞蝗全基因组序列图谱，为揭示蝗灾暴发机制，开发可持续性治理策略及新的控制方法提供了宝贵的遗传资源，也为推进飞蝗成为研究人类疾病和行为的生物医学模型奠定了重要基础。最新研究成果于2014年1月14日在《自然o通讯》（Nature Communications）杂志上在线发表。

飞蝗基因组大小约6.5GB，是人类基因组的两倍多，约是果蝇基因组的30倍，是目前科学家成功破译的最大动物基因组。在迄今为止被破译的近百个动物物种中，不乏个体外观较大的动物如小须鲸、藏羚羊、东北虎、白鳍豚，但超乎人们想象的是，个体如此之小的蝗虫竟拥有如此庞大的基因组。动物体形大小与基因组大小并不成比例，这是当今生物学界的一个未解之谜。

在本研究中，科研人员发现飞蝗之所以拥有如此巨大的基因组是由于自身转座因子的扩增以及这些因子相对缓慢的损失速度导致的，一般飞蝗基因组中转座因子损失的速度明显慢于其他昆虫。此外，在飞蝗基因组中，他们发现至少60%的区域存在着大量重复序列，约有2,639个重复序列家族，然而位于前十的重复序列家族总数仅占整个基因组序列的10%，这表明在飞蝗基因组中没有占据主导地位的家族基因。

飞蝗具有聚群和长距离迁徙能力。数以亿计的飞蝗能够突然且不可预计的形成蝗群，它们能够以每天数百千米的速度飞行甚至是穿越海洋。为了探究飞蝗强大的迁徙能力，科研人员发现与脂肪转移和抗氧化剂保护有关的基因发生了显著拷贝数扩增。这些基因包括7个PAT家族蛋白，11个脂肪酸结合蛋白，9个半胱氨酸抗氧化剂蛋白，12个谷胱甘肽巯基转移酶基因。此外，这些家族基因的部分基因在飞蝗飞行前后的脂肪体组织中发生了差异性表达，这说明这些家族基因可能在飞蝗飞行过程中扮演了重要的角色。由于飞行是昆虫消耗能量最大的运动之一，参与脂肪代谢的基因的扩增表明飞蝗已经形成了高效的能量供应系统，从而满足其在长距离飞行中高强度的能量消耗。

型变是一种依赖于密度的非遗传多型性，是蝗虫的一个重要特征，它涉及到一系列的生物和表型特性，包括身体颜色、形态、行为、生理、免疫反应及其它方面的变化。群体密度的增加可引发蝗虫从散居向群居的转变，导致蝗虫大量地聚集到一起，这种变化可快速发生、具有可逆性，并且在不同的亚种中转变的速度迥异。在本次研究中，科研人员首次揭示出两型转变的深层次原因，并表明型变与飞蝗周边及中枢神经系统中参与微管动力调控的多分子进程有关。科研人员表示调控神经可塑性的基因在表达量、DNA甲基化以及可变剪切方面均发生了明显变化。这些基因可能在控制飞蝗形成大的群体过程中发挥重要功能。

此外，科研人员还发现数百个潜在的杀虫剂目标基因，包括半胱氨酸环配体门控离子通道，G蛋白偶联受体以及一些致死基因，对今后控制蝗虫灾害提供了新的思路。飞蝗喜欢禾本科植物作为食物来源，研究人员发现飞蝗身体中的代谢解毒酶类（糖苷键转移酶）的基因数目在所有已测序昆虫中最为丰富，这类酶能够降解禾本科植物中存在的特定次生代谢物，为解释飞蝗以禾本科植物为食的原因提供了重要的科研依据。

Nature Communications   doi:10.1038/ncomms3957

The locust genome provides insight into swarm formation and long-distance flight

Xianhui Wang,Xiaodong Fang, Pengcheng Yang,Xuanting Jiang,Feng Jiang,Dejian Zhao, Bolei Li,Feng Cui,Jianing Wei,Chuan Ma,Yundan Wang,Jing He,Yuan Luo,  Zhifeng Wang,Xiaojiao Guo,Wei Guo,Xuesong Wang,Yi Zhang,Meiling Yang,Shuguang Hao et al.

Locusts are one of the world’s most destructive agricultural pests and represent a useful model system in entomology. Here we present a draft 6.5?Gb genome sequence of Locusta migratoria, which is the largest animal genome sequenced so far. Our findings indicate that the large genome size of L. migratoria is likely to be because of transposable element proliferation combined with slow rates of loss for these elements. Methylome and transcriptome analyses reveal complex regulatory mechanisms involved in microtubule dynamic-mediated synapse plasticity during phase change. We find significant expansion of gene families associated with energy consumption and detoxification, consistent with long-distance flight capacity and phytophagy. We report hundreds of potential insecticide target genes, including cys-loop ligand-gated ion channels, G-protein-coupled receptors and lethal genes. The L. migratoria genome sequence offers new insights into the biology and sustainable management of this pest species, and will promote its wide use as a model system.

MMB1116: FastPCR Software for PCR, In Silico PCR, and Oligonucleotide Assembly and Analysis

by Ruslan Kalendar, David Lee, Alan H. Schulman

 

Abstract

This chapter introduces the software FastPCR as an integrated tools environment for PCR primer and probe design. It also predicts oligonucleotide properties based on experimental studies of PCR efficiency. The software provides comprehensive facilities for designing primers for most PCR applications and their combinations, including standard, multiplex, long-distance, inverse, real-time, group-specific, unique, and overlap extension PCR for multi-fragment assembly in cloning, as well as bisulphite modification assays. It includes a program to design oligonucleotide sets for long sequence assembly by the ligase chain reaction. The in silico PCR primer or probe search includes comprehensive analyses of individual primers and primer pairs. It calculates the melting temperature for standard and degenerate oligonucleotides including LNA and other modifications, provides analyses for a set of primers with prediction of oligonucleotide properties, dimer and G/C-quadruplex detection, and linguistic complexity, and provides a dilution and resuspension calculator. The program includes various bioinformatics tools for analysis of sequences with CG or AT skew, of CG content and purine–pyrimidine skew, and of linguistic sequence complexity. It also permits generation of random DNA sequence and analysis of restriction enzymes of all types. It finds or creates restriction enzyme recognition sites for coding sequences and supports the clustering of sequences. It generates consensus sequences and analyzes sequence conservation. It performs efficient and complete detection of various repeat types and displays them. FastPCR allows for sequence file batch processing, which is essential for automation. The FastPCR software is available for download at http://primerdigital.com/fastpcr.html and online version at http://primerdigital.com/tools/pcr.html.

doi: 10.1007/978-1-62703-764-8_18

MMB1116: Quick and Clean Cloning

 

Fig. 1 Principle of the QC cloning strategy.
( a ) DNA fragments containing known and unknown flanking sequences are amplified by PCR using a primer homologous to an adaptor sequence (primer 1 and sequence A) attached to the end of the unknown sequence (U) and a primer homologous to a region of the known sequence (primer 2 and region K2). In addition to specific products, PCR amplification can yield nonspecific products (ns) and primer dimers.
( b ) Fragments are cloned via homology between sequences present in both the insert and the vector: sequences A and sequence K1 (also called the catching sequence, CS). Since primer 2 used for PCR amplification of the insert does not overlap with region K1, nonspecific products and primer dimers cannot be cloned

Abstract

Identification of unknown sequences that flank known sequences of interest requires PCR amplification of DNA fragments that contain the junction between the known and unknown flanking sequences. Since amplified products often contain a mixture of specific and nonspecific products, the quick and clean (QC) cloning procedure was developed to clone specific products only. QC cloning is a ligation-independent cloning procedure that relies on the exonuclease activity of T4 DNA polymerase to generate single-stranded extensions at the ends of the vector and insert. A specific feature of QC cloning is the use of vectors that contain a sequence called catching sequence that allows cloning specific products only. QC cloning is performed by a one-pot incubation of insert and vector in the presence of T4 DNA polymerase at room temperature for 10 min followed by direct transformation of the incubation mix in chemo-competent Escherichia coli cells.

doi: 10.1007/978-1-62703-764-8_3

Cell Metab：科学家发现糖尿病的新致病原因

Exeter Medical Schoo大学研究人员日前揭示了新生儿糖尿病的两个新的遗传原因。他们完成的这项研究发表在Cell Metabolism杂志上，进一步揭示了β细胞在胰腺中如何形成。

研究小组发现，对胰腺发育重要的两个特定基因的基因突变后，可引起新生儿糖尿病。这些发现将新生儿糖尿病的遗传原因数量增至20个。论文主要作者Sarah Flanagan表示：我们非常自豪能够给予参与研究的家庭解答，为什么他们的孩子有糖尿病。

新生儿糖尿病在孩子不到半岁时诊断，而其中一些患者增加了并发症，如肌肉无力和学习困难有或无癫痫。我们的新基因发现是关于β细胞在胰腺如何形成，这对研究操纵干细胞治愈疾病产生了重大影响。

研究英国糖尿病协会主任Alasdair Rankin说：除了进一步揭示新生儿糖尿病的遗传原因，新研究还提供答案给父母，为什么孩子会有这种罕见的疾病，这项工作有助于我们了解胰腺发育。

新生儿糖尿病是由影响胰岛素生成的基因发生变化引起的。这意味着，血糖在体内的水平危险性的升高。Exeter团队招募来自80多个国家的1200多名患者。这项研究集中在147名新生儿糖尿病的年轻人上，经过系统的筛选， 110例患者接受了基因诊断。

至于其余的37例患者，研究人员对人类胰腺发育的重要基因突变进行了筛选。突变发现在11名患者中存在，其中四个分别是两个基因NKX2- 2和MNX1（先前不知会导致新生儿糖尿病）中的一个。

对于其余121名（82％）接受基因诊断的患者，知道糖尿病的原因会导致得到更好的治疗，并给所有患者在将来怀孕时提供新生儿患糖尿病风险的重要信息。

doi:10.1016/j.cmet.2013.11.021

Analysis of Transcription Factors Key for Mouse Pancreatic Development Establishes NKX2-2 and MNX1 Mutations as Causes of Neonatal Diabetes in Man

Sarah E. Flanagan, Elisa De Franco, Hana Lango Allen, Michele Zerah, Majedah M. Abdul-Rasoul, Julie A. Edge, Helen Stewart, Elham Alamiri, Khalid Hussain, Sam Wallis, Liat de Vries, Oscar Rubio-Cabezas, Jayne A.L. Houghton, Emma L. Edghill, Ann-Marie Patch, Sian Ellard, Andrew T. Hattersley

Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.

Source from Bioon

J General Physiol：揭示尼古丁促进机体成瘾的分子机制

近日，刊登在国际杂志The Journal of General Physiology的两项研究成果中，来自国外的研究人员通过研究揭示了尼古丁如何利用人类机体的细胞机器促进人类成瘾，这将帮助研究者们开发新型的疗法来帮助个体实现戒烟。

据CDC信息显示，相比任何一种介质，烟草占据着世界上最大数量的可预防个体的死亡量，尼古丁是烟草中的有效成分，其可以激活名为nAChRs的受体；并不像其它滥用药物一样，尼古丁可以扮演分子伴侣的角色将受体固定于内质网中，从而增加受体在细胞表面的含量，而受体nAChRs在尼古丁成瘾过程中也扮演着重要角色，其可以降低吸烟患者患帕金森疾病的易感性。

包含∝6亚单位的nAChRs受体在许多特殊的大脑区域中含量丰富，研究者使用表达∝6（使用荧光蛋白标记的∝6）的小鼠进行研究揭示了，暴露于一定水平尼古丁中可以上调大脑区域中的∝6 nAChRs受体含量。

另外研究者也发现尼古丁上调∝6 nAChRs受体的能力依赖于COPI囊泡介导的∝6 nAChRs受体从高尔基体到内质网的逆向运输过程；研究者认为，高尔基体-内质网间的循环或许是尼古丁上调其它nAChRs受体的常见机制，通过对该机制进行控制或许可以帮助开发新型的戒烟手段以及帮助患者抵御帕金森疾病的神经保护策略。

COPI polices nicotine-mediated up-regulation of nicotinic receptors

doi:10.1085/jgp.201311136

Rene Anand

Mayans, Aztecs, and indigenous Americans cultivated tobacco for medicinal and religious purposes well over 2,000 years ago. The subsequent trade and industrial-scale production of tobacco have led to its global recreational use with devastating health consequences. It is currently responsible for the greatest number of preventable deaths worldwide by any single agent, estimated to be 5 million per year by the Center for Disease Control and Prevention. The active ingredient of tobacco, nicotine, efficiently permeates the blood brain barrier and activates neuronal nicotinic acetylcholine receptors (nAChRs) in the brain. In addition, nicotine exposure of the brain during childhood and adolescence is likely to increase susceptibility to neuropsychiatric and addiction disorders.

 

Nicotine exploits a COPI-mediated process for chaperone-mediated up-regulation of its receptors

doi:10.1085/jgp.201311102

Brandon J. Henderson¹, Rahul Srinivasan¹, Weston A. Nichols¹, Crystal N. Dilworth¹, Diana F. Gutierrez¹, Elisha D.W. Mackey¹, Sheri McKinney¹, Ryan M. Drenan², Christopher I. Richards³, and Henry A. Lester¹

Chronic exposure to nicotine up-regulates high sensitivity nicotinic acetylcholine receptors (nAChRs) in the brain. This up-regulation partially underlies addiction and may also contribute to protection against Parkinson’s disease. nAChRs containing the α6 subunit (α6* nAChRs) are expressed in neurons in several brain regions, but comparatively little is known about the effect of chronic nicotine on these nAChRs. We report here that nicotine up-regulates α6* nAChRs in several mouse brain regions (substantia nigra pars compacta, ventral tegmental area, medial habenula, and superior colliculus) and in neuroblastoma 2a cells. We present evidence that a coat protein complex I (COPI)-mediated process mediates this up-regulation of α6* or α4* nAChRs but does not participate in basal trafficking. We show that α6β2β3 nAChR up-regulation is prevented by mutating a putative COPI-binding motif in the β3 subunit or by inhibiting COPI. Similarly, a COPI-dependent process is required for up-regulation of α4β2 nAChRs by chronic nicotine but not for basal trafficking. Mutation of the putative COPI-binding motif or inhibition of COPI also results in reduced normalized Förster resonance energy transfer between α6β2β3 nAChRs and εCOP subunits. The discovery that nicotine exploits a COPI-dependent process to chaperone high sensitivity nAChRs is novel and suggests that this may be a common mechanism in the up-regulation of nAChRs in response to chronic nicotine.

Source from 生物谷

PNAS：揭示感冒病毒引发感染的分子机制

一般情况下我们一年会患2-3次感冒，但是普通感冒病毒感染机体的分子机制并不是完全清楚。近日，来自维也纳大学等处的研究者就清楚地解析了普通感冒病毒感染机体的分子机制，相关研究刊登于国际杂志PNAS上。

感冒病毒（鼻病毒）是一种较小的球形颗粒病毒，病毒包裹的遗传物质缠绕在蛋白质外壳（病毒衣壳）上，研究者在文章中揭示了病毒RNA释放衣壳以及有效感染人类机体的分子机制。

研究者Dieter Blaas说道，我们在文章中揭示了感冒病毒感染宿主细胞的分子结构，以及病毒RNA释放和复制的细节。研究者发现病毒RNA的构象以及其与病毒内在的衣壳间的相互作用不断发生着变化。

鼻病毒也会引发脊髓灰质炎和甲型肝炎的发生，该病毒属于微小核醣核酸病毒科，这项研究也为揭示其它疾病，比如甲肝等疾病的发病机理提供了一定思路。然而关于鼻病毒感染的很多机制目前仍不清楚，研究者表示，后期还需要进行大量研究工作来揭示病毒引发疾病的细节，这对于未来开发抵御病毒的药物或者新型疗法非常重要，本文也为后期的研究提供了一定的研究基础。

Uncoating of common cold virus is preceded by RNA switching as determined by X-ray and cryo-EM analyses of the subviral A-particle

doi:10.1073/pnas.1312128110

Angela Pickl-Herka,1,2, Daniel Luqueb,c,1, Laia Vives-Adriánd, Jordi Querol-Audíd, Damià Garrigae,3, Benes L. Trusf, Nuria Verdaguerd,4, Dieter Blaasa,4, and José R. Castónb,4

During infection, viruses undergo conformational changes that lead to delivery of their genome into host cytosol. In human rhinovirus A2, this conversion is triggered by exposure to acid pH in the endosome. The first subviral intermediate, the A-particle, is expanded and has lost the internal viral protein 4 (VP4), but retains its RNA genome. The nucleic acid is subsequently released, presumably through one of the large pores that open at the icosahedral twofold axes, and is transferred along a conduit in the endosomal membrane; the remaining empty capsids, termed B-particles, are shuttled to lysosomes for degradation. Previous structural analyses revealed important differences between the native protein shell and the empty capsid. Nonetheless, little is known of A-particle architecture or conformation of the RNA core. Using 3D cryo-electron microscopy and X-ray crystallography, we found notable changes in RNA–protein contacts during conversion of native virus into the A-particle uncoating intermediate. In the native virion, we confirmed interaction of nucleotide(s) with Trp38 of VP2 and identified additional contacts with the VP1 N terminus. Study of A-particle structure showed that the VP2 contact is maintained, that VP1 interactions are lost after exit of the VP1 N-terminal extension, and that the RNA also interacts with residues of the VP3 N terminus at the fivefold axis. These associations lead to formation of a well-ordered RNA layer beneath the protein shell, suggesting that these interactions guide ordered RNA egress.

Source from 生物谷

FASEB J：科学家解释年龄增长相关肥胖发生的机制

发表在2014年1月的FASEB Journal杂志上的一项最新研究中，科学家证实随着年龄的增长，棕色脂肪的产热活动减少。

棕色脂肪是“好”脂肪，坐落在我们的脖子的背部，帮助燃烧“坏的”白色脂肪。此外，研究人员还发现了一个可能的代谢开关，可以重新激活棕色脂肪。

Junko Sugatanii博士表示：研究是关于PAF / PAFR如何通过调控动物以及人类的棕色脂肪中β3 -AR生成信号控制UCP1的水平，研究可发现新的治疗靶点来治疗与肥胖症相关的代谢紊乱。

为了获得这一发现，科学家分析了两组小鼠。第一组血小板活化因子受体（PAFR）基因敲除小鼠。第二组是正常小鼠。与野生型同窝小鼠相比，PAFR缺陷的小鼠随着年龄增长发展了更严重的肥胖状态，具有更高的身体和附睾脂肪量。

从PAFR基因敲除小鼠模型结果显示，PAFR缺乏会导致褐色脂肪组织（BAT）功能障碍，从而诱发肥胖的发展，由于BAT产热作用受损。该研究阐明了PAF/PAF受体介导抗肥胖相关的分子机制，将有助发现肥胖症和相关病症如糖尿病，高血压，心脏疾病，癌症，不育和溃疡等治疗的新靶标。

 

Antiobese function of platelet-activating factor: increased adiposity in platelet-activating factor receptor-deficient mice with age
doi:10.1096/fj.13-233262

Junko Sugatani*,^†,¹, Satoshi Sadamitsu*, Masahiko Yamaguchi*, Yasuhiro Yamazaki*, Ryoko Higa*, Yoshiki Hattori*, Takahiro Uchida*, Akira Ikari*, Wataru Sugiyama^‡, Tatsuo Watanabe^†‡, Satoshi Ishii^§, Masao Miwa* and Takao Shimizu^‖

Platelet-activating factor receptor (PAFR)-deficient mice developed a more severe obese state characterized by higher body mass (～25%) and epididymal fat mass (～55%) with age than that of wild-type (WT) littermates. PAFR-deficient mice did not show changes in the expression of critical genes involved in anabolic and catabolic metabolism in adipose, liver, and muscle tissues between 6 and 36 wk. However, a 38-81% reduction in β3/β1-adrenergic receptor (AR) and uncoupling protein 1 (UCP1) mRNA and protein levels was observed in the interscapular brown adipose tissue (BAT) of PAFR-deficient mice. Whereas a single injection of the β3-adrenergic agonist, CL-316,243 (25 μg/kg) increased temperatures in the brown fat and rectums of WT mice, this increase in temperature was markedly suppressed in PAFR-deficient mice. Acetyl-CoA:lyso-platelet-activating factor (PAF) acetyltransferase, which is involved in PAF biosynthesis, and the PAF receptor were predominantly localized in BAT macrophages, whereas brown adipocytes possessed the enzyme and functional PAF receptors. The stimulation of brown adipocytes by PAF induced the expression of β3-AR mRNA and protein (1.5- and 1.9-fold, respectively), but not that of UCP1. These results indicate that obesity in PAFR-deficient mice resulted from impaired BAT activity and suggest that the antiobese function of PAF occurs through β3-AR/UCP1 expression in BAT.—Sugatani, J., Sadamitsu, S., Yamaguchi, M., Yamazaki, Y., Higa, R., Hattori, Y., Uchida, T., Ikari, A., Sugiyama, W., Watanabe, T., Ishii, S., Miwa, M., Shimizu, T. Antiobese function of platelet-activating factor: increased adiposity in platelet-activating factor receptor-deficient mice with age.

Source from 生物谷

Cell:转座子“跳跃”过程调控机制

[转载自生物谷]

“跳跃基因”的正式名称应该为转座子或转座元件，是一段能够插入到基因组新位置的DNA片段。人类基因组包含了大量古老的跳跃基因的垃圾片段，由于细胞要抑制跳跃基因的胡作非为，细胞进化出了针对转座子的调控机制。近期发表在Cell杂志上的文章揭示了调控跳跃基因的新机制。

大多数跳跃基因都会产生突变并不再”跳跃”，但是有一个基因例外–L1基因。该基因成功的复制自己，占据了人类DNA的20%。尽管很多拷贝发生突变，还是有很多拷贝处于活跃状态，这引起了遗传学家的兴趣。

Lixin Dai博士称人类细胞进化出限制跳跃基因活性的机制，因为它们越活跃就越容易破坏重要的基因，造成严重影响。Dai博士领导研究团队研究了L1的调控机制，发现两种类型的L1蛋白与RNA形成核糖核蛋白复合物，L1就是依靠该复合物进行”跳跃”。

为了进一步研究跳跃基因的调控机制，科学家分析了与该核糖核蛋白相互作用的蛋白，发现有37个蛋白与核糖核蛋白相互作用，于是科学家选择了两个蛋白进行进一步的研究。一个是UPF1，与质量控制有关，该蛋白监控RNA，会销毁发生错误的RNA。Dai博士称，当抑制UPF1功能的时候细胞会产生更多的L1的RNA和蛋白质。

另一个蛋白是PCNA，该蛋白帮助DNA复制。科学家发现PCNA能够与核糖核蛋白复合物中L1蛋白的一段重要序列结合，当科学家改变该结合序列后，L1不再”跳跃”。 Dai博士称，UPF1的作用是抑制L1活性，而PCNA看起来更像是协助L1进行跳跃。

Dai博士称我们的研究揭示了跳跃基因和细胞之间的博弈，表明细胞如何抑制跳跃基因的活性。我们将继续研究跳跃基因和细胞之间的”军备竞赛”。

doi: 10.1016/j.cell.2013.10.021

Affinity Proteomics Reveals Human Host Factors Implicated in Discrete Stages of LINE-1 Retrotransposition

Martin S. Taylor, John LaCava, Paolo Mita, Kelly R. Molloy, Cheng Ran Lisa Huang, Donghui Li, Emily M. Adney, Hua Jiang, Kathleen H. Burns, Brian T. Chait, Michael P. Rout, Jef D. Boeke, Lixin Dai.

LINE-1s are active human DNA parasites that are agents of genome dynamics in evolution and disease. These streamlined elements require host factors to complete their life cycles, whereas hosts have developed mechanisms to combat retrotransposition’s mutagenic effects. As such, endogenous L1 expression levels are extremely low, creating a roadblock for detailed interactomic analyses. Here, we describe a system to express and purify highly active L1 RNP complexes from human suspension cell culture and characterize the copurified proteome, identifying 37 high-confidence candidate interactors. These data sets include known interactors PABPC1 and MOV10 and, with in-cell imaging studies, suggest existence of at least three types of compositionally and functionally distinct L1 RNPs. Among the findings, UPF1, a key nonsense-mediated decay factor, and PCNA, the polymerase-delta-associated sliding DNA clamp, were identified and validated. PCNA interacts with ORF2p via a PIP box motif; mechanistic studies suggest that this occurs during or immediately after target-primed reverse transcription.

截止2013年10月已发表动物基因组信息收录

中文名	拉丁名	发表时间	刊物	科、属	基因组大小
秀丽隐杆线虫	Caenorhabditis elegans	1998.12	Science	小杆总科、Caenorhabditis亚属	97M
黑腹果蝇	Drosophila melanogaster	2000.03	Science	果蝇科、果蝇属	180M
冈比亚按蚊	Anopheles gambiae	2002.10	Science	蚊科、按蚊属	280M
小家鼠	Mus musculus	2002.12	Nature	鼠科	2.5 G
红鳍东方豚	Fugu rubripes	2002.12	Science	鲀科、东方鲀属	380M
玻璃海鞘	Ciona intestinalis	2002.12	Science	海鞘纲	150M
线虫	Caenorhabditis briggsae	2003.11	PLoS Biology	Caenorhabditis亚属	104M
大鼠	Rattus norvegicus	2004.04	Nature	啮齿目、鼠科	2.75 G
黑斑鲀	Tetraodon nigroviridis	2004.10	Nature	鲀科	340M
家蚕	Bombyx mori	2004.12	Science	鳞翅目、蚕蛾科	428.7 M
鸡	Gallus sonneratii	2004.12	Nature	雉科、原鸡属	1.06G
拟暗果蝇	Drosophila pseudoobscura	2005.01	Genome research	果蝇科、果蝇属	139M
克氏锥虫	Trypanosoma cruzi	2005.07	Science	锥虫属	67M
黑猩猩	Pan troglodytes	2005.09	Nature	猩猩科、黑猩猩属	2.7G
狗	Canis familiaris	2005.12	Nature	犬科、犬属	2.5 G
意蜂	Apis mellifera	2006.10	Nature	昆虫纲	236M
海胆	Strongylocentrotus purpuratus	2006.11	Science	海胆纲	1G
姥鲨	Callorhinchus milii	2007.04	Plos Biology	软骨鱼纲、银鲛目	0.91G
猕猴	Macaca mulatta	2007.04	Science	猴科、猕猴属	2.87G
短尾负鼠	Monodelphis domestica	2007.05	Nature	负鼠科、短尾负鼠属	3.4G
青鳉鱼	Oryzias latipes	2007.06	Nature	青鳉属	700M
伊蚊	Aedes aegypti	2007.06	Science	蚊科、伊蚊属	1376M
马来线虫	Brugia malayi	2007.07	Science	线虫纲	90M
海葵	Nematostella vectensis	2007.07	Science	海葵目	357M
12种果蝇基因组进化分析(10种新)	D.sechellia,D.simulans	2007.11	Nature	果蝇科、果蝇属
猫	Felis catus	2007.11	Genome Research	猫科、猫属	2.7G
赤拟谷盗	Tribolium castaneum	2008.04	Nature	鞘翅目、拟步行虫科、拟谷盗属	204M
鸭嘴兽	Ornithorhynchus anatinus	2008.05	Nature	鸭嘴兽科、鸭嘴兽属	1.84G
文昌鱼	Branchiostoma floridae	2008.06	Nature	文昌鱼科、文昌鱼属	520M
丝盘虫	Trichoplax adhaerens	2008.08	Nature	丝盘虫科、丝盘虫属	104M
根结线虫	Meloidogyne incognita	2008.08	Nature Biotechnology	线虫属	86M
古猛犸象	Mammuthus primigenius	2008.11	Nature	象科、猛犸象属	4.7G
牛	Bos taurus	2009.04	Science	牛科、牛属	2.87 G
裂吸虫	Schistosoma mansoni	2009.07	Nature	血吸虫属	360M
血吸虫	Schistosoma japonicum	2009.07	Nature	血吸虫属	397M
马	Equus caballus	2009.11	Science	马科、马属	2.7G
熊猫	Ailuropoda melanoleura	2010.01	Nature	熊科、大熊猫属	2.25G
金小蜂	Nasonia vitripennis, N. giraulti, N. longicornis	2010.01	Science	膜翅目、金小蜂科	295M
豌豆蚜虫	Acyrthosiphon pisum.	2010.02	PLoS Biology		517M
水螅	Hydra	2010.03	Nature	水螅科、水螅属	1.05G
非洲爪蟾	Xenopus tropicalis	2010.04	Science	负子蟾科、非洲爪蟾属	1.7 G
珍珠鸟	Taeniopygia guttata	2010.04	Nature	文鸟科、梅花雀属	1.2G
人类体虱	Pediculus humanus humanus	2010.07	PNAS	人虱属	110M
海绵	Amphimedon queenslandica	2010.08	Nature	多空动物门	190M
蚂蚁	Camponotus floridanus ,Harpegnathos saltator	2010.08	Science	蚁科	C. floridanus240 Mb; H. saltator330 Mb
火鸡	Meleagris gallopavo	2010.09	PLoS Biology	吐绶鸡科、吐绶鸡属	1.1 Gb
库蚊	Culex quinquefasciatus	2010.10	Nature	蚊科、库蚊属	540M
异体住囊虫	Oikopleura	2010.11	Science	脊索动物门、被囊动物亚门	148M
红毛猩猩	Pongo abelii 、Pongo pygmaeus	2011.01	Nature	猩猩科	3.09G
阿根廷蚁	Linepithema humile	2011.01	PNAS	蚁科	250.8M
红色收割蚁	Pogonomyrmex barbatus	2011.01	PNAS	蚁科	250–284 M
火蚁	Solenopsis invicta	2011.01	PNAS	蚁科	484.2M
水蚤	Daphnia pulex	2011.02	Science	甲壳纲，鳃足亚纲，水蚤科	200M
大头切叶蚁	Atta cephalotes	2011.02	PLoS Genetics	蚁科	300M
旋毛虫	Trichinella spiralis	2011.02	Nature Genetics	毛形科、毛形属	64M
袋獾	Sarcophilus harrisii	2011.06	PNAS	袋獾属	3.3G
顶切叶蚁	Acromyrmex echinatior	2011.06	Genome Research	顶切叶蚁属	313M
鹿角珊瑚	Acropora digitifera	2011.07	Nature	珊瑚虫纲	420M
巨蟒	Python molurus bivittatus	2011.07	Genome Biology	爬行纲	1.4G
大西洋鳕鱼	Gadus morhua	2011.08	Nature	鳕形目、鳕属	830M
澳大利亚袋鼠	Macropus eugenii	2011.08	Genome Biology	有袋目、袋鼠科	2.9G
绿蜥蜴	Anolis carolinensis	2011.09	Nature	爬行纲、有鳞目	1.78G
裸鼹鼠	Heterocephalus glaber	2011.10	Nature	啮齿目\裸鼹鼠属	2.6G
食蟹猴和中国恒河猴	Macaca fascicularis,Macaca mulatta lasiota	2011.10	Nature Biotechnology	猴科、猕猴属	2.85G
猪蛔虫	Ascaris suum	2011.10	Nature	蛔虫属	272M
二斑叶螨(棉红蜘蛛)	Tetranychus urticae	2011.11	Nature	叶螨科、叶螨属	90M
帝王蝶	Danaus plexippus	2011.11	Cell	斑蝶属	273M
指猴(夜狐猴)	Daubentonia madagascariensis	2011.12	Genome Biology and Evolution	指猴属	3G
鲶鱼	Ictalurus punctatus	2011.12	BMC Genomics	鲶科、鲶属	1G
埃及血吸虫	Schistosoma haematobium	2012.01	Nature Genetics	血吸虫属	385M
中华肝吸虫	Clonorchis sinensis	2011.10	Genome Biology	线虫纲	516M
鳄鱼	Crocodylus siamensis	2012.01	Genome Biology	爬行纲、鳄目	2.5G
马氏珠母贝	Pinctada fucata	2012.02	DNA Research	珍珠贝科、珠母贝属	1150M
大猩猩	Gorilla gorilla gorilla	2012.03	Nature	猩猩科	3.04G
三刺鱼	Gasterosteus aculeatus	2012.04	Nature	刺鱼目、刺鱼科、刺鱼属	463M
诗神袖蝶	Heliconius melpomene	2012.05	Nature	蛱蝶科、 釉蛱蝶属	269M
倭黑猩猩	Pan paniscus	2012.06	Nature	猩猩科、黑猩猩属	2.7G
虎皮鹦鹉	Melopsittacus undulatus	2012.07	Nature Biotechnology	鹦鹉科、虎皮鹦鹉属	1.2G
牦牛	Bos grunniens	2012.07	Nature Genetics	牛科、牛属	2.66G
北极熊	Ursus maritimus	2012.07	PNAS	熊科、棕熊属	2.53G
间日疟原虫	Plasmodium vivax	2012.08	Nature Genetics	疟原虫科、疟原虫属	Brazil I 28.87Mb; India VII 29.25Mb; Mauritania I 28.43Mb; North Korean 29.65Mb
食蟹猴疟原虫	Plasmodium cynomolgi	2012.08	Nature Genetics	疟原虫科、疟原虫属	26.2Mb
勇地雀	Geospiza fortis	2012.08	GigaScience	地雀属	1.07 Gb
牡蛎	Crassostrea gigas	2012.09	Nature	软体动物门、牡蛎科	559 Mb
姬鹟	Ficedula albicollis	2012.10	Nature	鹟科、姬鹟属	1.13Gb
毛里求斯果蝇	Drosophila mauritiana	2012.10	Genome Research	果蝇科、果蝇属
骆驼	Camelus bactrianus	2012.11	Nature Communications	骆驼科、骆驼属、双峰驼种	2.38Gb
家猪	Sus scrofa	2012.11	Nature	猪科、猪属	2.6Gb
五指山猪	Sus scrofa	2012.11	GigaScience	猪科、猪属	2.6 Gb
帽贝、海蠕虫、淡水水蛭	Lottia gigantea, Capitella teleta, Helobdella robusta	2012.12	Nature	软体动物、腹足纲；环节动物、多毛纲；环节动物、蛭纲、水蛭科	348Mb,324Mb,228Mb
蝙蝠	Pteropus alecto，Myotis davidii	2012.12	Science	狐蝠科；蝙蝠科、鼠耳蝠属	2.00Gb，1.94Gb
家山羊	Capra hircus	2012.12	Nature Biotechnology	牛科、羊亚科、山羊属	2.92G
小菜蛾	Plutella xylostella	2013.01	Nature Genetics	鳞翅目、菜蛾科	343Mb
鸽子	Columba livia	2013.01	Science	鸠鸽科、鸽属	1.3 Gb
树鼩	Tupaia belangeri	2013.02	Nature Communications	树鼩科、树鼩属	3.2Gb
七鳃鳗	Petromyzon marinus	2013.02	Nature Genetics	七鳃鳗科	816Mb
四种绦虫	Echinococcus multilocularis;E. granulosus;Taenia solium ;Hymenolepis microstoma	2013.03	Nature	扁形动物门、绦虫纲	115-141Mb
游隼、猎隼	Falco peregrinus;Falco cherrug	2013.03	Nature	隼科、隼属	1.2Gb
西部锦龟	Chrysemys picta bellii	2013.03	Genome Biology	沼泽龟科、锦龟属	2.59Gb
山松甲虫	Dendroctonus ponderosae Hopkins	2013.03	Genome Biology	鞘翅目、小蠹科	208 Mb
月光鱼	Xiphophorus maculatus	2013.03	Nature Genetics	花鳉科、剑尾鱼属	750–950 Mb
地山雀	Pseudopodoces humilis	2013.03	Genome Biology	山雀科、地山雀属	1.1 Gb
斑马鱼	Danio rerio	2013.04	Nature	鲤科、鱼丹属	1.4 Gb
腔棘鱼	Latimeria chalumnae	2013.04	Nature	矛尾鱼科	2.86 Gb
中华鳖和绿海龟	Pelodiscus sinensis ;Chelonia mydas	2013.04	Nature Genetics	鳖科、中华鳖属；海龟科、海龟属	2.21 Gb;2.24Gb
藏羚羊	Pantholops hodgsonii	2013.05	Nature Communications	牛科、藏羚属	2.75 Gb
绯红金刚鹦鹉	Ara macao	2013.05	PLoS ONE	鹦鹉科、金刚鹦鹉属	1.11–1.16 Gbp
北京鸭	Anas platyrhynchos	2013.06	Nature Genetics	鸭科、鸭属	1.2 Gb
按蚊	Anopheles darlingi	2013.06	Nucleic Acids Research	蚊科、按蚊属	201 Mb
太平洋蓝鳍金枪鱼	Thunnus orientalis	2013.06	PNAS	鲭科、金枪鱼属	800 Mb
地山雀	Parus humilis	2013.07	Nature Communications	山雀科、地山雀属	1.08G
蛭形轮虫	Adineta vaga	2013.07	Nature	轮虫纲	244 Mb
扬子鳄	Alligator sinensis	2013.08	Cell Research	短吻鳄科、短吻鳄属	2.3 Gb
中国仓鼠	Cricetulus griseus	2013.08	Nature Biotechnology	仓鼠科	2.33 Gb
布氏鼠耳蝠	Myotis brandtii	2013.08	Nature Communications	蝙蝠科、鼠耳蝠属	2 Gb
捻转血矛线虫	Haemonchus contortus	2013.08	Genome Biology	毛圆科、血矛属	320 Mb
细粒棘球绦虫	Echinococcus granulosus	2013.09	Nature Genetics	带科、棘球属	151.6 Mb
东北虎	Panthera tigris	2013.09	Nature Communications	猫科、豹属	2.4G
东亚钳蝎	Mesobuthus martensii	2013.10	Nature Communications	钳蝎科、钳蝎属	1.3G