第第9章：章：1.有哪些因素会导致有哪些因素会导致DNA突变和损伤？突变和损伤？2. DNA突变和损伤其修复机制突变和损伤其修复机制,每种修复机制中设计涉每种修复机制中设计涉及的关键蛋白或酶有哪些，他们的主要作用是什么。及的关键蛋白或酶有哪些，他们的主要作用是什么。第第10章章:1.同源重组的两个主要的模型是什么？同源重组的两个主要的模型是什么？2.同源重组过程中的关键步骤有哪些？同源重组过程中的关键步骤有哪些？3.大肠杆菌中在同源重组过程中涉及的关键蛋白有哪些，大肠杆菌中在同源重组过程中涉及的关键蛋白有哪些，它们的主要作用是什么？它们的主要作用是什么？Chapter 11上一节内容回顾上一节内容回顾Site-Specific Recombination & Transposition of DNAChapter 11Although DNA replication, repair, homologous recombination occur with high fidelity to ensure the genome identity between generations, there are genetic processes that rearrange DNA sequences and thus lead to a more dynamic genome structure.Chapter 11GenomeStable:Dynamic:DNA replicationrepair homologous recombinationConservative site-specific recombination (CSSR)Transpositional recombination (Transposition) Impact on the chromosome structure and functionKey mechanism:RecombinaseRecognize GatherCleavageRejoinInverse or moveChapter 11aaTwo classes of genetic recombination for DNA rearrangement:Conservative site-specific recombination (CSSR): recombination between two defined sequence elementsTranspositional recombination (Transposition): recombination between specific sequences and nonspecific DNA sitesChapter 11Figure 11-1Conservative site-specific recombinationTranspositional recombinationChapter 11OUTLINE1. Conservative Site-Specific Recombination.2. Biological Roles of Site-Specific Recombination3. Transposition4. Examples of Transposable Elements and Their Regulation5. V(D)J RecombinationChapter 11Topic 1 Conservative Site-Specific Recombination(CSSR)CSSR is recombination between two defined sequence elements1.Exchange of non-homologous sequences at specific DNA sites(what) 2.Mediated by proteins that recognize specific DNA sequences. (how)Chapter 111-1 CSSR occurs at specific DNA sequences in the target DNAnCSSR (conserved site-specific recombination) is responsible for many reactions in which a defined segment of DNA is rearranged. Chapter 11Conservative Site-Specific Recombination1.specific DNA sites in the target DNA2.Site-Specific RecombinaseFigure 11-2 Integration of genome into the chromosome of the host cell.Chapter 11CSSR can generate three different types of DNA rearrangementsFigure 11-3Chapter 11Recombination site Structures involved in CSSR :1.Recognition sequences2.Crossover region: asymmetricPolarity Inverted repeatDirect repeatFigure 11-4 Structures involved in CSSRChapter 111-2 Site-specific recombinases cleave and rejoin DNA using a covalent protein-DNA intermediatenTherere two families of conservative site-specific recombinases: 1. Serine Recombinases 2. Tyrosine RecombinasesChapter 11Figure 11-5 Covalent-intermediate mechanism used by the serine and tyrosine recombinasesChapter 11n蛋白质蛋白质-DNA共价中间体中，蛋白质和共价中间体中，蛋白质和DNA之间之间的共价连接保留了断裂的磷酸二酯键的能量。这的共价连接保留了断裂的磷酸二酯键的能量。这样样DNA链可以通过逆转断裂过程被重新连接。链可以通过逆转断裂过程被重新连接。n这种机制的特性提供了保守性位点特异性重组，这种机制的特性提供了保守性位点特异性重组，被称为被称为“保守保守”是因为反应中被断开的每个是因为反应中被断开的每个DNA键都被重组酶重新连接起来，而键都被重组酶重新连接起来，而DNA在被重组酶在被重组酶断开并重新连接的过程中不需要其他的能量。断开并重新连接的过程中不需要其他的能量。n这种机制也常见于这种机制也常见于DNA拓扑异构酶和拓扑异构酶和Spo11，后，后者运用这种机制在减数分裂期间诱导者运用这种机制在减数分裂期间诱导DNA双链断双链断裂引发同源重组。裂引发同源重组。Chapter 111-3 Serine recombinases introduce DSB in DNA and then swap strands to promote recombinationnFirst , the serine recombinases cleave all four strandsnSecond, DNA swap occursnFinally, the serine recombinases are liberated and they seal the DNA strandsChapter 11Recombination by a serine recombinaseFigure 11-6Chapter 111-4 Tyrosine recombinases break and rejoin one pair of DNA strands at a timenIn contrast to the serine recombinases, the tyrosine recombinases cleave and rejoin two DNA strands first, and only then cleave and rejoin the other two strands.Chapter 11Recombination by a tyrosine recombinaseFigure 11-7Chapter 111-5 Structure of tyrosine recombinases bound to DNA reveal the mechanism of DNA exchangenCre is a tyrosine recombinase.nCre is an phage P1-encoded protein, functioning to circularize the linear phage genome during infection.nThe recombination sites of Cre is lox sites. Cre-lox is sufficient for recombination.Chapter 11Figure 11-9 Mechanism of site-specific recombination by the Cre recombinase.Chapter 11Topic 2 Biological roles of site-specific recombinationChapter 111.Many phage insert their DNA into the host chromosome during infection using this recombination mechanism. Example: l l phage2.Alter gene expression. Example: Salmonella Hin recombinase3.Maintain the structural integrity of circular DNA molecules during cycles of DNA replication. Example: resolvase that resolves dimer to monomer.Chapter 11nAll reactions depend critically on the assembly of the recombinase protein on the DNA and bring together of the two recombination sites.nSome recombination requires only the recombinase and its recognition sequence for such an assembly; some requires accessory proteins including Architectural Proteins that bind specific DNA sequences and bend the DNA.The general themes of site-specific recombinationChapter 11 2-1 l l integrase promotes the integration and Excision of a Viral Genome into the Host Cell ChromosomenBacteriophage l infects a host bacterium and would establish a lysogen ,which requires the integration of phage DNA into host chromosomen To integrate, l Int catalyzes recombination between two specific sitesattachment (att) sitesn attP site is on the phage DNA and attB site is on the bacterial genomen lInt is a tyrosine recombinase, and the mechanism of strand exchange follows the pathway described above for the Cre proteinChapter 11 l l genome integration. Recombination always occurs at exactly the same sequence within two recombination sites, one on the phage DNA, and the other on the bacterial DNA.Chapter 11Int (l(l-encoded integrase)Xis (l l-encoded excisionase) IHF ( (integration host factor encoded by bacteria)Figure 11-10Chapter 11tyrosine recombinaseInt binding site C- Int binding site H-IHF binding site X-Xis binding site P- Int binding siteCrossover regionsPhage genomeBacterial genomeIHF binding to the H site bends the DNA to allow one molecue of lInt to bind both the P1 and C1site. Figure 11-11Chapter 11 Phage l l excision requires a new DNA-binding proteinnPhage l l excision requires an architectural protein called Xis, which is phage-encoded.nXis binds to the integrated attR sites to stimulate excision and to inhibit integration.Chapter 112-2 The Hin recombinase inverts a segment of DNA allowing expression of alternative genesn The Salmonella Hin recombinase inverts a segment of the bacterial chromosome to allow expression of two alternative sets of genes.nHin recombinase is an example of programmed rearrangements in bacterianIn the case of Hin inversion, recombination is used to help the bacteria evade the host immune systemnHin is a serine recombinase which promotes inversion Chapter 11fljB encodes H2 flagellinfljA encodes a transcriptional repressor of H1 flagellinFigure 11-13 DNA inversion by the Hin recombinase of Salmonella.Chapter 11Hin recombination requires a DNA enhancernHin recombination requires a DNA enhancer in addition to the hix sites.nEnhancer function requires the bacterial Fis protein. n the enhancer-Fis complex activates the catalytic steps of recombination. n Hin-catalyzed inversion is not highly regulated, rather, inversion occurs stochastically.Chapter 11AFis: factor for inversion stimulation, contact with Hin to form the invertasome（倒位体）（倒位体）ENSURE THAT recombination occurs on same DNA molecule.Figure 11-14Chapter 112-3 Recombinase converts multimeric circular DNA molecules into monomersnCircular DNA molecules sometimes form dimers and even higher multimeric forms during the process of homologous recombination. nSite-specific recombinases (sometimes called resolvases) can resolve dimers and larger multimers into monomers.Chapter 11Figure 11-15 Circular DNA molecules can form multimersChapter 11n Xer recombinase is a tyrosine.n Xer catalyzes the monomerization of bacterial chromosomes and of many bacterial plasmids.nXer is a heterotetramer, containing two subunits of XerC and two subunits of XerD.n XerC and XerD recognize different sequence.n The directional regulation of Xer-mediated recombination is achieved through the interaction between the Xer recombinase and a cell diversion protein called FtsK .Chapter 11Xer recombinaseBox 11-2 Fig1 The dimer only resolves when XerD is activated by the presence of FtsKChapter 11Topic 3 Transposition (转座转座)nTransposition is a specific form of genetic recombination that moves certain genetic elements from one DNA site to another.nThese mobile genetic elements are called transposable elements or transposons.n Movement occurs through recombination between the DNA sequences at the ends of the transposons and a sequence in the host DNA with little sequence selectivity.Chapter 11 3-1 Some genetic elements move to new chromosomal locations by transpositionFigure 11-16 Transposition of a mobile genetic element to a new site in host DNAChapter 11The transposons can insert within genes or regulatory sequence of a gene, which results in the completely disruption of gene function. They can also insert within the regulatory sequences of a gene where their presence may lead to changes in how that gene is expressed.Transposable elements are present in the genomes of all life-forms. (1) transposon-related sequences can make up huge fractions of the genome of an organism. (2) the transposon content in different genomes is highly variable.Chapter 11Transposition in genome: occurrence and distributionGreen: mostly composed of transposon-related sequences.Purple: cellular genes.Figure 11-17 Chapter 113-2 There are three principle classes of transposable elementsChapter 11怎么怎么来的来的Chapter 11 3-2-1 DNA transposons carry a transposase gene, flanked by recombination sitesnRecombination sites are at the two ends of the transposon and are inverted repeated sequences varying in length from 25 to a few hundred bp.nThe recombinase responsible for transposition are usually called transposases or integrases.nSometimes they carry a few additional genes. Example, many bacterial DNA transposons carry antibiotic resistance gene.Chapter 11Transposons exist as both autonomous and nonautonomous elementsnAutonomous transposons: carry a pair of terminal inverted repeats and a transposase gene; function independentlynNonautonomous transposons: carry the terminal inverted repeats but not the functional transposase; need the transposase encoded by autonomous transposons to enable transposition3-2-2 Viral-like retrotransposons and retroviruses carry terminal repeat sequences and two genes important for recombination1.Inverted terminal repeat sequences for recombinase binding are embedded within long terminal repeats (LTRs), being organized on the two ends of the elements as direct repeats.2.Reverse transcriptase (RT;反转录酶反转录酶), using an RNA template to synthesize DNA.3.Integrase (整合酶整合酶) or the transposase(转座酶转座酶)Chapter 113-2-3 Poly-A retrotransposons look like genesnDo not have the inverted terminal repeats. nOn end is called 5 UTR (untranslated region), the other end is 3 UTR followed by a stretch of A-T base pairs called the poly-A sequence. Flanked by short target site duplication.nCarry two genes. ORF1 encodes an RNA-binding proteins. ORF2 encodes a protein with both reverse transcriptase (RT) and endonuclease activity. Truncated elements lacking complete 5 UTR?Chapter 113-3 DNA transposition by a cut-and-paste mechanism nThe movement of a DNA transposon by a non-replicative mechanism called cut-and-paste transposition.1.First , transposase binds to the inverted terminal repeats at the end of the transposon and brings the two ends of the transposon DNA together to generate a stable protein-DNA complex called the synaptic complex or transpososome.Chapter 112. Next, the transposon DNA is excised from its original location in the genome.3. Then, the 3-OH ends of the transopon DNA attack the DNA phosphodiester bonds at the site of the new insertion, this DNA segment is called the target DNA.4. At last, the transposon DNA is covalently joined to the DNA at the target site by DNA strand tranfer. This reaction introduced a nick into the target DNA.Chapter 11Chapter 11Figure 11-19 The cut-and-paste mechanism of transposition.转座酶断裂转座酶断裂DNA链的位链的位置在转座子置在转座子DNA和它所和它所插入的宿主序插入的宿主序列间的连接处，列间的连接处，叫叫flanking host DNA。1.Two introduced nick are filled by a DNA repair polymerase (encoded by the host cell) and a DNA ligase2.Filling in the gap gives rise to the target site duplications that flank transposonsThe intermediate in cut-and-paste transposition is finished by gap repairChapter 111. An enzyme other than transposase can be used to cleave the nontransfered strand2. The transposase itself cleave the nontransfered strand by using an unusual DNA transesterification(转酯基转酯基) mechanism3. DNA cleavage via a transesterification reaction can also occur between two ends of the transposon 3-4 There are multiple mechanisms for cleaving the nontransferred strand during DNA transpositionChapter 11FIGURE12-21 Three mechanisms for cleaving the nontransferred strand.3-5 DNA transposition by a replicative mechanismnFirst, the transposase protein is assembled on the two ends of the transposon DNA to generate a transpososome.nThen, DNA is cleaved at the ends of the transposon DNA.Figure 11-22Chapter 11n Then, the 3OH ends of the trsnsposon DNA are joined to the target sites by the DNA strand transfer reaction, which generate a doubly branched DNA moleculen At last, The two DNA branches within this intermediate have the structure of a replication fork, and the DNA synthesis is proceededn This replication reaction generates two copies of the transposon DNAFigure 11-22Chapter 113-6 Viral-like retrotransposons and retroviruses move using an RNA intermediatenRecombination for retroelements involves an RNA intermediate.1.A cycle of transposition starts with transcription of the retrotransposon (or retroviral) DNA sequence into RNA by cellular RNA polymerase. Transcription initiates at a promoter sequence within one of the LTRs.2. The RNA is then reverse transcribed to generate the cDNAChapter 113. The cDNA is recognized by Integrase and recombinate with a new target DNA site4. Integrase assembles on the ends of this cDNA and cleaves a few nucleotides off the 3 ends of each strand 5. Integrase catalyzes the insertion of cleaved 3 ends into a DNA target site in the host cell genome using the DNA strand transfer reaction.6. Gap repair reaction generates target-site duplications.Chapter 11Figure 11-23Chapter 11Mechanism of retroviral integration and transposition of viral-like retrotransposons.RNA没有携带全长的没有携带全长的LTR序列，序列，在逆转录过在逆转录过程中，有两个内部引程中，有两个内部引物合成和两个单链转物合成和两个单链转换反应（见框换反应（见框11-3）。）。3-7 DNA transposases and retroviral integrases are members of a protein superfamilynMany different tranposases and integrases carry a catalytic domain that has a common three-dimensional shapenThis domain contains two Asp (D) and a Glu (E) nThe tranposase/integrase proteins use this same site to catalyze both the DNA cleavage and the DNA strand transfernTranposases and integrases are only active when assembled into a synaptic complex, also called a transpososome, on DNAChapter 11Tn5 tranposase Mu tranposase RSV integraseFIGURE 12-24 Similarities of catalytic domains of transposases and integrases. 3-8 Poly-A Retrotransposition move by a “reverse splicing” mechanism The Poly-A Retrotransposons use an RNA intermediate but us e a mechanism different than that used by the viral-like elements. This mechanism is called target site primed reverse transcription 1. First, the DNA of an integrated element is transcripted by a cellular RNA polymerase 2. Then, newly synthesized RNA is exported to cytoplasm to produce ORF1 and ORF2 proteins Chapter 113. The protein-RNA complex then reenters the nuclease and associates with the cellular DNA. (The ORF2 protein has both a DNA endonuclease activity and a reverse transcriptase activity.)4.The endonuclease initiates the intergration reaction by introducing a nick in the chromosomal DNA ( ploy T). 5. The 3OH DNA end generated by the nicking action then serves as the primer for reverse transcription of the element RNA.Chapter 11Figure 11-26Chapter 11Transposition of a poly-A retrotransposon by target site-primed reverse transcriptionFigure 11-26Topic 4 Examples of transposable enements and their regulationnTwo types of regulation appear as recurring themes:1.Transposons control the number of their copies present in a given cell.2.Trnasposons control target site choice.Chapter 114-1 IS4-family transposons are compact elements with multiple mechanisms for copy number controlnTn10 transposes via the cut-and paste mechanism, using the DNA hairpin strategy to cleave the nontransfered strands.nTn10 limits its copy number in any given cell by strategies that restrict its transposition frequency. One mechanism is the use of an antisense RNA to control the expression of the transposase gene. nBy this mechanism, cells that carry more copes of Tn10 will transcribe more of the antisense RNA, which in turn will limit expression of the transposase gene. The transposition frequency will, therefore, be very low in such a strain.Chapter 11Tn10nStructure:Mechanism: cut-and-paste mechanismChapter 11Anti-sense RNAAntisense regulation of Tn10 expressionFigure 11-28Chapter 114-2 Tn10 transposition is coupled to cellular DNA replicationnBacteria methylate their DNA at GATC sites and GATC sites are hemimethylated for a few minutes.nIt is during the brief periodwhen the Tn10 DNA is hemimethylatedthat transposition is more likely to occur.nBoth RNA polymerase and transposase bind more tightly to the hemimethylated sequences than to their fully methylated versions. As a result, when the DNA is hemimethylated, the transposase gene is most efficiently expressed, and the transposase protein binds most efficiently to the DNA.Chapter 11Transposition of Tn10 after passage of a replication fork.Figure 11-29Chapter 114-3 Phage Mu is an extremely robust transposonnRobust transposonnTransposition way is similar to retrovirusesnCarry two genes related with transpotion: MuA MuBnRegulation: target immunity to avoid transposing into its own DNA 15kbChapter 11Figure 11-30Early steps of Mu transpositionChapter 11Topic 5 V(D)J recombinationnThe principal mechanism cells use to generate antibodies and T cell receptors with such diversity relies on a specialized set of DNA rearrangement reactions known as V(D)J recombinationChapter 11Overview of the process of V(D)J recombinationChapter 11Figure 11-35The early events in V(D)J recombination occur by a mechanism similar to transposon excisionnRecombination sequences, called recombination signal sequences, flank the gene segments that are assembled by V(D)J recombination.nRecombination always occurs between a pair of recombination signal sequences which are organized as inverted repeats flanking the DNA segments that are destined to be joined.Chapter 11Fig 11-36Recombination signal sequences recognized in V(D)J recombination.nFirst, reconbinase recognizes the recombination signal sequences and pairs the two sites to form a protein-DNA synaptic complex.nThen, the RAG1 proteins within this complex introduce single-stranded breaks in the DNA at each of the junctions between the recombination signal sequence and the gene segment that will be rearranged.nThen, this 3OH DNA end attacks the opposite strand of the DNA double helix, which results in the generation of a hairpin DNA end.Chapter 11The V(D)J recombination pathwayChapter 11Figure 11-37Key Point1. 概念：位点特异性重组概念：位点特异性重组(保守性位点特异性重组保守性位点特异性重组)、DNA 转座、转座子、转座、转座子、 V(D)J重组、自主转座子和重组、自主转座子和非自主转座子等。非自主转座子等。2. 丝氨酸丝氨酸/络氨酸重组酶的重组机制络氨酸重组酶的重组机制3. DNA转座的特点。转座的特点。4. 三种主要转座子的结构特点。三种主要转座子的结构特点。5. DNA转座的剪切转座的剪切-粘贴机制和复制机制。粘贴机制和复制机制。Completely understand two animations about site-specific recombination and transposition of DNA.本章要点 n1.名词：位点特异性重组名词：位点特异性重组(保守性位点特异性重组保守性位点特异性重组)、DNA 转座、转座子、转座、转座子、 V(D)J重组、自主转座子和非自主转座子等。重组、自主转座子和非自主转座子等。2. CSSR产生哪几种不同类型的产生哪几种不同类型的DNA重排？重排？3.CSSR的重组位点的结构特征如何？的重组位点的结构特征如何？4.CSSR中的重组酶有那两种主要的类型，他们的作用机制分别是什么？中的重组酶有那两种主要的类型，他们的作用机制分别是什么？5.转座因子对插入位点是否有序列选择性，都可以插入到什么位置，会产生什么转座因子对插入位点是否有序列选择性，都可以插入到什么位置，会产生什么样的相应的后果？样的相应的后果？6.转座因子有哪三种基本类型，每种类型转座因子的结构特点和转座机制分别是转座因子有哪三种基本类型，每种类型转座因子的结构特点和转座机制分别是什么？什么？7. 概念：概念：2. 丝氨酸丝氨酸/络氨酸的重组机制络氨酸的重组机制8. DNA转座的特点转座的特点。9 三种主要转座子的结构特点。三种主要转座子的结构特点。10. DNA转座的剪切转座的剪切-粘贴机制和复制机制。粘贴机制和复制机制。思考题思考题n1 名词：位点特异性重组、转座名词：位点特异性重组、转座n2 位点特异性重组，重组位点的结构特点，重组位点特异性重组，重组位点的结构特点，重组酶的两个家族是什么，他们的作用特点是什么酶的两个家族是什么，他们的作用特点是什么n3 转座的类型（复制型和非复制型），根据转座转座的类型（复制型和非复制型），根据转座的的的的DNA 插入的目的序列的不同，会产生什么用插入的目的序列的不同，会产生什么用的不同的后果。的不同的后果。n4 三种基本的的转座因子都是什么，他们的结构三种基本的的转座因子都是什么，他们的结构特征是什么。特征是什么。n5 转座的两种机制是什么，其中剪切转座的两种机制是什么，其中剪切-粘贴的具体粘贴的具体机制如何。机制如何。染色体重排与染色体重排与Y-染色体进化染色体进化1) 人类人类Y-染色体系由染色体系由X-染色体进化而来染色体进化而来.2) 在三亿年前人类祖先与鸟类分开之后在三亿年前人类祖先与鸟类分开之后, X-染染色体发生了第一次倒位色体发生了第一次倒位, 由此开始由此开始Y-染色体的染色体的进化进化. 3) 人类人类Y-染色体共发生了染色体共发生了4次倒位次倒位, 并伴随大量并伴随大量的基因突变与缺失的基因突变与缺失.4) Y染色体产生之际曾含有染色体产生之际曾含有1438个基因，但到个基因，但到目前为止目前为止, , 其中的其中的1393个基因已经消失个基因已经消失, ,只剩只剩下下45个基因个基因 , 平均平均每百万年丢失每百万年丢失4.6个基因个基因.Y染色体上的蛋白质编码基因染色体上的蛋白质编码基因新的研究确认了新的研究确认了X染色体上有染色体上有1098个个蛋白质编码基因蛋白质编码基因，而这，而这1098个基因个基因中只有中只有54个在对应的个在对应的Y染色体上有染色体上有相应功能的等位基因，而且相应功能的等位基因，而且Y染色体染色体比比X染色体小得多，染色体小得多，Y染色体上仅有染色体上仅有大约大约78个基因个基因。Y Y染色体是一个对个体生存染色体是一个对个体生存不必要的染色体不必要的染色体Y Y染色体是惟一一个对个体生存不必要的染色体。染色体是惟一一个对个体生存不必要的染色体。人如果没有人如果没有X X染色体，或者没有其他任何一对常染色体，或者没有其他任何一对常染色体，就无法出生，在胚胎期就会死亡。而没染色体，就无法出生，在胚胎期就会死亡。而没有有Y Y染色体却对个体生存没有关系，比如女性都染色体却对个体生存没有关系，比如女性都没有没有Y Y染色体，却照样可以健康长寿。其他染色染色体，却照样可以健康长寿。其他染色体一般互相依靠，但是它们不依靠体一般互相依靠，但是它们不依靠Y Y染色体。人染色体。人类必须面对一个有可能导致自身灭亡的问题类必须面对一个有可能导致自身灭亡的问题 男性男性Y Y染色体的功能正在逐渐退化，它所掌控的染色体的功能正在逐渐退化，它所掌控的基因正在逐渐减少基因正在逐渐减少。 袋鼠袋鼠Y染色体只有一个基因染色体只有一个基因-SRYAs a result of this process, for humans 95% of Y chromosome is unable to recombine, and Ychromosome contains only 70 to 300 working genes versus more than 1000 for X chromosome. For some other animals, the degradation of Y chromosome is even more severe. For example, the Y chromosome in kangaroos contains only the SRY gene. Y染色体进化四步曲染色体进化四步曲新基因的产生新基因的产生主要有以下新基因的产生主要有以下5种种方式方式:1) 基因加倍之后的基因加倍之后的趋异趋异, 这类基因基本保持原有的基因这类基因基本保持原有的基因功能功能, 但往往获得了新的表达模式但往往获得了新的表达模式. 这是新基因产生的主要方式这是新基因产生的主要方式.2) 结构域结构域洗牌洗牌, 即不同的结构域加倍或重组即不同的结构域加倍或重组, 产生具有产生具有创新功能的基因创新功能的基因. 真核生物约真核生物约19%的基因产生于外显的基因产生于外显子洗牌子洗牌.3) 逆转录及其随后的趋异或逆转录及其随后的趋异或重排重排.4) 基因基因裂变与融合裂变与融合, 由一个基因分裂成两个不同的基因由一个基因分裂成两个不同的基因, 或两个或多个基因融合组成一个新的基因或两个或多个基因融合组成一个新的基因. 原核生物原核生物约约0.5%的基因由此产生的基因由此产生.5) 嬗变嬗变, 由非编码顺序转变为编码顺序由非编码顺序转变为编码顺序.基因组扩张重复顺序的增加高等生物基因组重复顺序的扩张是一个极高等生物基因组重复顺序的扩张是一个极其普遍的现象其普遍的现象, 这些重复顺的扩张主要起因这些重复顺的扩张主要起因于于: 1) 重复顺序之间的不等交换重复顺序之间的不等交换; 2) DNA的转座的转座 3) 逆转录转座逆转录转座基因的进化速率是不相同的 丹麦研究人员发现，人类和黑猩猩丹麦研究人员发现，人类和黑猩猩500500万年前在进化途中分道扬万年前在进化途中分道扬镳后，两者的基因图谱中进化最快的都是与免疫、细胞凋亡和精子发镳后，两者的基因图谱中进化最快的都是与免疫、细胞凋亡和精子发育相关的基因育相关的基因. . 丹麦哥本哈根大学的研究人员对人类和黑猩猩具有对等功能的丹麦哥本哈根大学的研究人员对人类和黑猩猩具有对等功能的1373113731个基因进行了研究，结果发现，在人类和黑猩猩的进化树中，个基因进行了研究，结果发现，在人类和黑猩猩的进化树中，与免疫、细胞凋亡和精子发育相关的基因演变的速度甚至比随机突变与免疫、细胞凋亡和精子发育相关的基因演变的速度甚至比随机突变还要快。换句话说，在自然选择的过程中，这些基因是进化最快的。还要快。换句话说，在自然选择的过程中，这些基因是进化最快的。 研究人员分析，病毒和其他病原体的进化速度很快，人类免疫系研究人员分析，病毒和其他病原体的进化速度很快，人类免疫系统不断受到新出现的病毒的威胁，因此，与抵抗疾病相关的基因进化统不断受到新出现的病毒的威胁，因此，与抵抗疾病相关的基因进化迅速是理所当然的。而与细胞凋亡和精子相关的基因进化快则让研究迅速是理所当然的。而与细胞凋亡和精子相关的基因进化快则让研究人员感到意外。凋亡是细胞死亡的机制之一，是生理性细胞死亡。由人员感到意外。凋亡是细胞死亡的机制之一，是生理性细胞死亡。由于细胞凋亡会减少健康成熟的精子，因此，研究人员推测，与凋亡和于细胞凋亡会减少健康成熟的精子，因此，研究人员推测，与凋亡和精子相关的基因进化快是因为精子细胞自身进化的推动。精子相关的基因进化快是因为精子细胞自身进化的推动。实际应用nAdenovirusnMVA