基因是DNA Genes are DNA（清华大学课件） 英文版.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Chapter 1,Genes are DNA,DNA,是遗传物质,DNA,为双螺旋,DNA,的复制是半保留的,通过碱基配对进行核酸杂交,突变改变了,DNA,的序列,突变集中于热点,顺反子是单个,DNA,片断,多重等位基因的种类,DNA,的物理交换导致重组,遗传密码是三联体,细菌的基因和蛋白是共线性的,顺式作用点和反式作用分子,遗传信息可由,DNA,或者,RNA,提供,本章,主要内容,Figure 1.1 A brief history of genetics.,1.1,Introduction,Genes are DNA,Avirulent,mutants,of a virus have lost the capacity to infect a host cell productively,that is,to make more virus.,Transfection,of,eukaryotic,cells is the acquisition of new genetic markers by incorporation of added DNA.,Transforming principle,is DNA that is taken up by a bacterium and whose expression then changes the properties of the recipient cell.,1.2,DNA is the genetic material,Figure 1.2 The transforming principle is DNA.,1.2,DNA is the genetic material,Figure 1.3 The genetic material of phage T2 is DNA.,1.2,DNA is the genetic material,Figure 1.4,Eukaryotic,cells can acquire a new phenotype as the result of,transfection,by added DNA.,1.2,DNA is the genetic material,Antiparallel,strands of the double helix are organized in opposite orientation,so that the 5 end of one strand is aligned with the 3 end of the other strand.,Base pairing,describes the specific(complementary)interactions of adenine with,thymine,or of cytosine with,thymine,in a DNA double helix(the former is replaced by adenine with,uracil,in double helical RNA).,Complementary,base pairs are defined by the pairing reactions in double helical nucleic acids(A with T in DNA or with U in RNA,and C with G).,Supercoiling,describes the coiling of a closed duplex DNA in space so that it crosses over its own axis.,1.3,DNA is a double helix,Figure 1.5 A,polynucleotide,chain consists of a series of 5,-3,sugar-phosphate links that form a backbone from which the bases protrude,1.3,DNA is a double helix,Figure 1.6 The double helix maintains a constant width because,purines,always face,pyrimidines,in the complementary A-T and G-C base pairs.The sequence in the figure is T-A,C-G,A-T,G-C.,1.3,DNA is a double helix,Figure 1.7 Flat base pairs lie perpendicular to the sugar-phosphate backbone.,1.3,DNA is a double helix,Figure 1.8 The two strands of DNA form a double helix.,1.3,DNA is a double helix,DNA,polymerases,are enzymes that synthesize a daughter strand(s)of DNA(under direction from a DNA template).May be involved in repair or replication.,DNAases,are enzymes that attack bonds in DNA.,Endonucleases,cleave bonds within a nucleic acid chain;they may be specific for RNA or for single-stranded or double-stranded DNA.,Exonucleases,cleave nucleotides one at a time from the end of a,polynucleotide,chain;they may be specific for either the 5 or 3 end of DNA or RNA.,Parental strands,of DNA are the two complementary strands of duplex DNA before replication.,1.4,DNA replication is,semicon,-,servative,Replication fork,is the point at which strands of parental duplex DNA are separated so that replication can proceed.,Ribonucleases,are enzymes that degrade RNA.,Exo,(,ribo,)nucleases work progressively,typically degrading one base at a time from the 3 end toward the 5 end.Endo(,ribo,)nucleases make single cuts within the RNA chain.,RNA,polymerases,are enzymes that synthesize RNA using a DNA template(formally described as DNA-dependent RNA,polymerases,).,RNAases,are enzymes that degrade RNA.,Semiconservative,replication,is accomplished by separation of the strands of a parental duplex,each then acting as a template for synthesis of a complementary strand.,1.4,DNA replication is,semicon,-,servative,Figure 1.9 Base pairing provides the mechanism for replicating DNA.,1.4,DNA replication is,semicon,-,servative,Figure 1.10 Replication of DNA is,semiconservative,.,1.4,DNA replication is,semicon,-,servative,Figure 1.11 The replication fork is the region of DNA in which there is a transition from the unwound parental duplex to the newly replicated daughter duplexes.,1.4,DNA replication is,semiconservative,Denaturation,of DNA or RNA describes its conversion from the double-stranded to the single-stranded state;separation of the strands is most often accomplished by heating.,Hybridization,is the pairing of complementary RNA and DNA strands to give an RNA-DNA hybrid.,Melting,of DNA means its,denaturation,.,Melting temperature,of DNA is the mid-point of the transition when duplex DNA to denatured by heating to separate into single strands.,Renaturation,is the,reassociation,of denatured complementary single strands of a DNA double helix.,1.5,Nucleic acids hybridize by base pairing,Figure 1.12 Base pairing occurs in duplex DNA and also in intra-and inter-molecular interactions in single-stranded RNA(or DNA).,1.5,Nucleic acids hybridize by base pairing,Figure 1.13 Denatured single strands of DNA can,renature,to give the duplex form.,1.5,Nucleic acids hybridize by base pairing,Figure 1.14 Filter hybridization establishes whether a solution of denatured DNA(or RNA)contains sequences complementary to the strands immobilized on the filter.,1.5,Nucleic acids hybridize by base pairing,Background level,of mutation describes the rate at which sequence changes accumulate in the genome of an organism.It reflects the balance between the occurrence spontaneous mutations and their,remomval,by repair systems,and is characteristic for any species.,Deletions,are generated by removal of a sequence of DNA,the regions on either side being joined together.result from the action of a,mutagen,(which may act directly on the bases in DNA)or indirectly,but in either case the result is a change in the sequence of DNA.are identified by the presence of an additional stretch of base pairs in DNA.,1.6,Mutations change the sequence of DNA,Leaky,mutants have some residual function,either because the mutant protein is partially active(in the case of a,missense,mutation),or because a small amount of wild-type protein is made(in the case of a nonsense mutation).,Mutagens,increase the rate of mutation by inducing changes in DNA sequence,directly or indirectly.,Point mutations,are changes involving single base pairs.,Revertants,are derived by reversion of a mutant cell or organism.,Spontaneous mutations,occur as the result of natural effects,due either to mistakes in DNA replication or to environmental damage.,1.6,Mutations change the sequence of DNA,Suppression,describes the occurrence of changes that eliminate the effects of a mutation without reversing the original change in DNA.,Suppressor,(,extragenic,)is usually a gene coding a mutant,tRNA,that reads the mutated,codon,either in the sense of the original,codon,or to give an acceptable substitute for the original meaning.,Transition,is a mutation in which one,pyrimidine,is substituted by the other or in which one,purine,is substituted for the other.,Transversion,is a mutation in which a,purine,is replaced by a,pyrimidine,or vice versa.,1.6,Mutations change the sequence of DNA,Figure 1.15 Mutations can be induced by chemical modification of a base.,1.6,Mutations change the sequence of DNA,Figure 1.16 Mutations can be induced by the incorporation of base analogs into DNA.,1.6,Mutations change the sequence of DNA,Back mutation,reverses the effect of a mutation that had inactivated a gene;thus it restores wild type.,Forward mutations,inactivate a wild-type gene.,Hotspot,is a site at which the frequency of mutation(or recombination)is very much increased.,Modified bases,are all those except the usual four from which DNA(T,C,A,G)or RNA(U,C,A,G)are synthesized;they result from,postsynthetic,changes in the nucleic acid.,Neutral substitutions,in a protein are those changes of amino acids that do not affect activity.,Silent mutations,do not change the product of a gene.,1.7 Mutations are concentrated at hotspots,Figure 1.17 Spontaneous mutations occur throughout the,lacI,gene of,E.,coli,but are concentrated at a hotspot.,1.7 Mutations are concentrated at hotspots,Figure 1.18 The,deamination,of 5-,methylcytosine,produces,thymine,(causing C-G to T-A transitions),while the,deamination,of cytosine produces,uracil,(which usually is removed and then replaced by cytosine).,1.7 Mutations are concentrated at hotspots,Figure 1.15 Mutations can be induced by chemical modification of a base.,1.7 Mutations are concentrated at hotspots,Cistron,is the genetic unit defined by the,cis,/trans test;equivalent to,gene,.,Complementation group,is a series of mutations unable to complement when tested in,pairwise,combinations in trans;defines a genetic unit(the,cistron,).,Gene(,cistron,),is the segment of DNA involved in producing a polypeptide chain;it includes regions preceding and following the coding region(leader and trailer)as well as intervening sequences(,introns,)between individual coding segments(,exons,).,One gene,:,one enzyme hypothesis,is the basis of modern genetics:that a gene is a stretch of DNA coding for a single polypeptide chain.,1.8,A,cistron,is a single stretch of DNA,Figure 1.19 Genes code for proteins;dominance is explained by the properties of mutant proteins.A recessive allele does not contribute to the phenotype because it produces no protein(or protein that is nonfunctional).,1.8,A,cistron,is a single stretch of DNA,Figure 1.20 The,cistron,is defined by the complementation test.Genes are represented by bars;red stars identify sites of mutation.,1.8,A,cistron,is a single stretch of DNA,Gain-of-function,mutation represents acquisition of a new activity.It is dominant.,Leaky,mutants have some residual function,either because the mutant protein is partially active(in the case of a,missense,mutation),or because a small amount of wild-type protein is made(in the case of a nonsense mutation).,Loss-of-function,mutation inactivates a gene.It is recessive.Null mutation completely eliminates the function of a gene,usually because it has been physically deleted.,Polymorphism,refers to the simultaneous occurrence in the population of genomes showing allelic variations(as seen either in alleles producing different phenotypes or-for example-in changes in DNA affecting the restriction pattern).,1.9 The nature of multiple alleles,Figure 1.19 Genes code for proteins;dominance is explained by the properties of mutant proteins.A recessive allele does not contribute to the phenotype because it produces no protein(or protein that is nonfunctional).,1.9 The nature of multiple alleles,Figure 1.21 The,w,locus has an extensive series of alleles,whose phenotypes extend from wild-type(red)color to complete lack of pigment.,1.9 The nature of multiple alleles,Figure 1.22 The ABO blood group locus codes for a,galactosyltransferase,whose specificity determines the blood group.,1.9 The nature of multiple alleles,Bivalent,is the structure containing all four,chromatids,(two representing each homologue)at the start of meiosis.,Breakage and reunion,describes the mode of genetic recombination,in which two DNA duplex molecules are broken at corresponding points and then rejoined crosswise(involving formation of a length of,heteroduplex,DNA around the site of joining).,Chiasma,(pl.,chiasmata,),is a site at which two homologous chromosomes appear to have exchanged material during meiosis.,Crossing-over,describes the reciprocal exchange of material between chromosomes that occurs during meiosis and is responsible for genetic recombination.,Hybrid DNA,is another term for,heteroduplex,DNA.,1.10 Recombination occurs by physical exchange of DNA,Figure 1.23,Chiasma,formation is responsible for generating recombinants.,1.10 Recombination occurs by physical exchange of DNA,Figure 1.24 Recombination involves pairing between complementary strands of the two parental duplex,DNAs,.,1.10 Recombination occurs by physical exchange of DNA,Figure 1.13 Denatured single strands of DNA can,renature,to give the duplex form.,1.10 Recombination occurs by physical exchange of DNA,Codon,is a triplet of nucleotides that represents an amino acid or a termination signal.,Frameshift,mutation results from an insertion or deletion that changes the phase of triplets,so that all,codons,are misread after the site of mutation.,Genetic code,is the correspondence between triplets in DNA(or RNA)and amino acids in protein.,Initiation,codon,is a special,codon,(usually AUG)used to start synthesis of a protein.,ORF,is an open reading frame;presumed likely to code for a protein.,Reading frame,is one of three possible ways of reading a nucleotide sequence as a series of triplets.,Suppressor,(,extragenic,)is usually a gene coding a mutant,tRNA,that reads the mutated,codon,either in the sense of the original,codon,or to give an acceptable substitute for the original meaning.,Termination,codon,is one of three(UAG,UAA,UGA)that causes protein synthesis to terminate.,1.11 The genetic code is triplet-,Key terms,Figure 1.25,Frameshift,mutations show that the genetic code is read in triplets from a fixed starting point.,1.11,The genetic code is triplet,Figure 1.26 An open reading frame starts with AUG and continues in triplets to a termination,codon,.Blocked reading frames may be interrupted frequently by termination,codons,.,1.11 The genetic code is triplet,Coding region,is a part of the gene that represents a protein sequence.,Leader,of a protein is a short N-terminal sequence responsible for passage into or through a membrane.,RNA splicing,is the process of excising the sequences in RNA that correspond to,introns,so that the sequences corresponding to,exons,are connected into a continuous,mRNA,.,Trailer,is a,nontranslated,sequence at the 3 end of an,mRNA,following the termination,codon,.,Transcription,is synthesis of RNA on a DNA template.,Translation,is synthesis of protein on the,mRNA,template.,1.12 The relationship between coding sequences and proteins,Figure 1.27 The recombination map of the,tryptophan synthetase,gene corresponds with the amino acid sequence of the protein.,1.12,The relationship between coding sequences and proteins,Figure 1.28 RNA is synthesized by using one strand of DNA as a template for complementary base pairing.,1.12 The relationship between coding sequences and proteins,Figure 1.29 The gene may be longer than the sequence coding for protein.,1.12 The relationship between coding sequences and proteins,Figure 1.30 Gene expression is a multistage process.,1.12,The relationship between coding sequences and proteins,Figure 2.10 Interrupted genes are expressed via a precursor RNA.,Introns,are removed when the,exons,are spliced together.The,mRNA,has only the sequences of the,exons,.,1.12,The relationship between coding sequences and proteins,Figure 5.16,Eukaryotic mRNA,is modified by addition of a cap to the 5,end and poly(A)to the 3,end.,1.12,The relationship between coding sequences and proteins,cis,-,configuration describes two sites on the same molecule of DNA.,Trans-,configuration of two sites refers to their presence on two different molecules of DNA(chromosomes).,1.13,cis,-acting sites and,trans,-acting molecules,Figure 1.20 The,cistron,is defined by the complement-,ation,test.Genes are represented by bars;red stars identify sites of