转座子,转座机制

1、 Bacterial TransposonsA transposable element 转座因子 moves from one DNA address to anotherOriginally discovered in maize, transposons have been found in all kinds of organisms Bacteria Plants HumansDiscovery of Bacterial Transposons Phage coat is made of protein Always has the same volume 同体积 DNA is mu

2、ch denser than protein DNA密度大More DNA in phage, denser phage 若DNA含量 高，其密度就大Extra DNAs that can inactivate a gene by inserting into it were the first transposons discovered in bacteria 发现gal基因的失活是因为插入了一段野生型基因中没有的 DNA，这就是转座子These transposons are called insertion sequences (ISs) 插入序列Insertion Sequences

3、Insertion sequences are the simplest type of bacterial transposon IS是最简单的细菌转座子They contain only the elements necessary for their own transposition 仅包含满足自身转座需要的因子： Short inverted repeats at their ends末端短的反向重复序列 At least 2 genes coding for an enzyme, transposase that carries out transposition由至少两个基因编码

4、的转座酶 Transposition involves: Duplication of a short sequence in the target DNA复制 靶DNA的一段短序列 One copy of this sequence flanks the insertion sequence on each side after transposition转座后插入序列 侧翼各有一个拷贝Generating Host DNA Direct RepeatsComplex TransposonsThe term “selfish DNA” implies that insertion seque

5、nces and other transposons replicate at the expense of their hosts, providing no value in return 插入序列或者其它转座子是自私的Some transposons do carry genes that are valuable to their hosts, antibioticresistance is among most familiar 但有的转座子可 以为宿主提供有益的东西，如抗生素抗性基因Antibiotic Resistance and TransposonsTransposition

6、 MechanismsTransposons are sometimes called “jumping genes”, DNA doesnt always leave one place for another 转座子也被叫作跳跃基因（但有误导）When it does, nonreplicative transposition 非复制式 转座 “Cut and paste” Both strands of original DNA move together from 1 place to another without replicating Transposition frequent

7、ly involves DNAreplication 1 copy remains at original site New copy inserts at the new site Replicative transposition 复制式转座 “Copy and paste”Replicative Transposition of Tn323-11Detailed Tn3 TranspositionNonreplicative Transposition Eukaryotic TransposonsTransposons have powerful selective forces on

8、their side 转座子会赋予寄主强大的选择压Transposons carry genes that are an advantage to their hosts 转座子携带有利的基因 Their host can multiply at the expense of completing organisms 因此寄主能在竞争中繁殖自己 Can multiply the transposons along with rest of their DNA 并与寄主DNA的其它部分一起繁殖转座子If transposons do not have host advantage, can re

9、plicate themselves within their hosts 即使对宿主不利，它们可以自私的复制Examples of Transposable ElementsVariegation in the color of maize kernels is caused by multiple reversions of an unstable mutation in the C locus, responsible for kernel color 玉米籽粒色班是由 C位点的非稳定突变的多次回复突变引起的， C位点控制籽粒的颜色 Mutation and its reversion

10、result from Ds(dissociation) element Ds因子 Transposes into the C gene转座到C基因中 Mutates it 使其突变 Transposes out again, revert to wild type 再从C基 因中转座出去，回复成野生型Ds and Ac of Maize Ds cannot transpose on its own Ds自身并不能发生转座Must have help from an autonomous transposon, Ac (for activator) 必须由自主因子 Ac才能转座 Ac supp

11、lies transposase提供转座酶 Ds is an Ac element with most of its middle removed Ds因子或多或少缺失 Ac因子中的一部分片段 Ds needs A pair of inverted terminal repeats一对末端反向重复序列 Adjacent short sequences that Ac transposase can recognize 与其相连的一段短的可以被 Ac转座酶所识别的序列Transposable Elements in MaizeStructures of Ac and DsP ElementsTh

12、e P-M system of hybrid dysgenesis in Drosophila is caused by conjunction of 2 factors 果蝇杂种败育的P-M系统是由两个相连的因子引起的 : Transposable element (P) contributed by the male父本 提供的转座因子P M cytoplasm contributed by the female allows transposition of the P element 母本提供的M细胞质，这种细胞质能使P因子发生转座Hybrid offspring of P males

13、 and M females suffer multiple transpositions of P element P系雄性和M系雌性杂交后代中P因子多次发生转座Damaging chromosomal mutations are caused that render the hybrids sterile 转座引起染色体的损伤突变，导致杂种后代不育Rearrangement of Immunoglobulin Genes免疫球蛋白基因的重排Mammalian genes use a process that closely resembles transposition for与转座相似的

14、过程产生 : B cell antibodies B细胞抗体 T cell receptors T细胞受体Recombinases involved in these processes have similar structures 两个过程中的重组酶也很相似Antibody StructureImmune SystemEnormous diversity of immune system is generated by 3 basic mechanisms产生10亿种抗体 与外来物质发生作用，这些免疫系统通过 3个基本机制产生了巨大的多样性 : Assembling genes for a

15、ntibody light chains and heavy chains from 2 or 3 component parts 2个或3个部分被用于组装抗体的重链和轻链 Joining the gene parts by an imprecise mechanism that can delete bases or add extra bases 通过减少甚至增加碱基对的非精确连接机制来重组基因的各部分从而改变基因 Causing a high rate of somatic mutations, probably during proliferation of a clone if im

16、mune cells 可能在免疫细胞的增殖过程中引起体细胞的高额突变，产生差异轻微的基因Rearrangement of Antibody Light Chain GeneAntibody Heavy Chain Coding RegionsRecombination Signals 重组信号 The recombination signal sequences(RSSs) in V(D)J recombination consist of重 组信号序列包括: Heptamer 7聚体 Nonamer 9聚体 Separated by 12-bp or 23-bp spacers 间隔12bp

17、或者23bpRecombination occurs only between a 12 signal and a 23 signal 重组只能发生在 12信号和23信号之间Guarantees that only 1 of each coding region is incorporated into the rearranged gene 以确保重组基因中仅整合每个编码区中的一个The Recombinase Recombination-activating gene (RAG-1)stimulated V(D)J joining activity in vivoAnother gene

18、tightly liked to RAG-1 also works in V(D)J joining, RAG-2These genes, RAG-1 and RAG-2, are expressed only in pre-B and pre-T cellsMechanism of V(D)J RecombinationRAG1 and RAG2 introduce single-strand nicks into DNA adjacent to either a 12 signal or 23 signal 在DNA单链上切口Results in transesterification w

19、here newly created 3-OH group转酯反应发生Hairpins then break in an imprecise way that allows joining of coding regions with loss of bases or gain of extra bases 形成发夹结构以非精确的方式断裂，通过碱基的增减连接编码区重组信号序列 Retrotransposons 反转录转座子 Retrotransposons replicate through anRNA intermediate 反转录转座子通过一个 RNA中间体进行复制Retrotransposons resemble retroviruses类似 于反转录病毒 Retroviruses can cause tumors in vertebrates引起脊椎动物的肿瘤 Some retroviruses cause diseases such asAIDS 或者爱滋Before studying retrot