02 第一章 基因是DNA（Genes are DNA）.ppt

第1页：Chapter 1 Genes are DNA

Chapter 1 Genes are DNA

第2页：第1章内容提要：本章主要内容

• 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

第3页：A brief history of genetics

Figure 1.1 A brief history of genetics.

第4页：Genes are DNA

Genes are DNA

第5页：Key terms: Avirulent mutants of a virus

Avirulent mutants of a virus

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

Transfection of eukaryotic cells is the acquisition of new genetic markers by incorp or at ion of added DNA.

Transforming principle

Transforming principle is DNA that is taken up by a bacterium and whose expression then changes the properties of the recipient cell.

第6页：The transforming principle is DNA

Figure 1.2 The transforming principle is DNA.

第7页：The genetic material of phage T2 is DNA

Figure 1.3 The genetic material of phage T2 is DNA.

第8页：Eukaryotic cells can acquire a new phenotype

Figure 1.4 Eukaryotic cells can acquire a new phenotype as the result of transfection by added DNA.

第9页：Key terms: Antiparallel strands of the double

Antiparallel strands of the double helix

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

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

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

Supercoiling describes the coiling of a closed duplex DNA in space so that it crosses over its own axis.

第10页：A poly nucleotide chain consists of a series

Figure 1.5 A poly nucleotide chain consists of a series of 5′-3′sugar-phosphate links that form a backbone from which the bases protrude.

第11页：The double helix maintains a constant width

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.

第12页：Flat base pairs lie perpendicular to

Figure 1.7 Flat base pairs lie perpendicular to the sugar-phosphate backbone.

第13页：The two strands of DNA form a double helix

Figure 1.8 The two strands of DNA form a double helix.

第14页：Key terms: DNA polymerases, DNAases, Endonucleases

DNA polymerases

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

DNAases are enzymes that attack bonds in DNA.

Endonucleases

Endonucleases cleave bonds within a nucleic acid chain; they may be specific for RNA or for single-stranded or double-stranded DNA.

Exonucleases

Exonucleases cleave nucleotides one at a time from the end of a poly nucleotide chain; they may be specific for either the 5′ or 3′ end of DNA or RNA.

Parental strands of DNA

Parental strands of DNA are the two complementary strands of duplex DNA before replication.

第15页：Key terms: Replication fork, Ribo nucleases, RNA

Replication fork

Replication fork is the point at which strands of parental duplex DNA are separated so that replication can proceed.

Ribo nucleases

Ribo nucleases 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

RNA polymerases are enzymes that synthesize RNA using a DNA template (formally described as DNA-dependent RNA polymerases).

RNAases

RNAases are enzymes that degrade RNA.

Semiconservative replication

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.

第16页：Base pairing provides the mechanism

Figure 1.9 Base pairing provides the mechanism for replicating DNA.

第17页：Replication of DNA is semiconservative

Figure 1.10 Replication of DNA is semiconservative.

第18页：The replication fork is the region of DNA

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.

第19页：Key terms: Denatur at ion of DNA or RNA

Denatur at ion of DNA or RNA

Denatur at ion 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

Hybridization is the pairing of complementary RNA and DNA strands to give an RNA-DNA hybrid.

Melting of DNA

Melting of DNA means its denatur at ion.

Melting temperature of DNA

Melting temperature of DNA is the mid-point of the transition when duplex DNA to denatured by heating to separate into single strands. Renatur at ion is the reassoci at ion of denatured complementary single strands of a DNA double helix.

第20页：Base pairing occurs in duplex DNA and also

Figure 1.12 Base pairing occurs in duplex DNA and also in intra-and inter-molecular interactions in single-stranded RNA (or DNA).

第21页：Denatured single strands of DNA can renature

Figure 1.13 Denatured single strands of DNA can renature to give the duplex form.

第22页：Filter hybridization establishes whether a soluti

Figure 1.14 Filter hybridization establishes whether a soluti on of denatured DNA (or RNA) contains sequences complementary to the strands immobilized on the filter.

第23页：Key terms: Background levelof mutation, Deletions

Background levelof mutation

Background levelof 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

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.

第24页：Key terms: Leaky mutants, Point mutations

Leaky mutants

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).

Point mutations

Point mutations are changes involving single base pairs.

Spontaneous mutations

Spontaneous mutations occur as the result of natural effects, due either to mistakes in DNA replication or to environmental damage.

Mutagens increase the rate of mutation by inducing changes in DNA sequence, directly or indirectly.

Revertantsare derived by reversi on of a mutant cell or organism.

第25页：Key terms: Suppression, Suppressor (extragenic)

Suppression

Suppression describes the occurrence of changes that eliminate the effects of a mutation without reversing the original change in DNA.

Suppressor (extragenic)

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 accept able substitute for the original meaning.

Transition

Transition is a mutation in which one pyrimidine is substituted by the other or in which one purine is substituted for the other.

Transversi on

Transversi on is a mutation in which a purine is replaced by a pyrimidine or vice versa.

第26页：Mutations can be induced by chemical modification

Figure 1.15 Mutations can be induced by chemical modification of a base.

第27页：Mutations can be induced by the incorp or at ion

Figure 1.16 Mutations can be induced by the incorp or at ion of base analogs into DNA.

第28页：Key terms: Hotspot, Modified bases, Neutral

Hotspot

Hotspot is a site at which the frequency of mutation (or recombination) is very much increased.

Modified bases

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

Neutral substitutions in a protein are those changes of amino acids that do not affect activity.

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.

Silent mutations do not change the product of a gene.

第29页：Spontaneous mutations occur throughout the lac

Figure 1.17 Spontaneous mutations occur throughout the lac Igene of E. coli, but are concentrated at a hotspot.

第30页：The deamin at ion of 5-methylcytosine produces

Figure 1.18 The deamin at ion of 5-methylcytosine produces thymine (causing C-G to T-A transitions), while the deamin at ion of cytosine produces uracil (which usually is removed and then replaced by cytosine).

第31页：Mutations can be induced by chemical modification

Figure 1.15 Mutations can be induced by chemical modification of a base.

第32页：Key terms: Cistron, Complement at ion group

Cistron

Cistron is the genetic unit defined by the cis/trans test; equivalent to gene.

Complement at ion group

Complement at ion group is a series of mutations unable to complement when tested in pairwise combin at ions 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.

第33页：Genes code for proteins; dominance is explained

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).

第34页：The cistron is defined by the complement at ion

Figure 1.20 The cistron is defined by the complement at ion test. Genes are represented by bars; red stars identify sites of mutation.

第35页：Key terms: Gain-of-functi on mutation, Leaky

Gain-of-functi on mutation

Gain-of-functi on mutation represents acquisition of a new activity. It is dominant.

Leaky mutants

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).

Null mutation completely eliminates the

Null mutation completely eliminates the function of a gene, usually because it has been physically deleted.

Polymorphism

Polymorphism refers to the simultaneous occurrence in the popul at ion of genomes showing allelic vari at ions (as seen either in alleles producing different phenotypes or-for example-in changes in DNA affecting the restriction pattern).

Loss-of-functi on mutation inactivates a gene. It is recessive.

第36页：Genes code for proteins; dominance is explained

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).

第37页：The wlocus has an extensive series of alleles

Figure 1.21 The wlocus has an extensive series of alleles, whose phenotypes extend from wild-type (red) color to complete lack of pigment.

第38页：The ABO blood group locus codes for

Figure 1.22 The ABO blood group locus codes for a galactosyltransferase whose specificity determines the blood group.

第39页：Key terms: Bivalent, Breakage and reunion

Bivalent

Bivalent is the structure containing all four chromatids (two representing each homologue) at the start of meiosis.

Breakage and reunion

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).

Crossing-over

Crossing-over describes the reciprocal exchange of material between chromosomes that occurs during meiosis and is responsible for genetic recombination.

Hybrid DNA

Hybrid DNA is another term for heteroduplex DNA.

Chiasma (pl. chi as mata)is a site at which two homologous chromosomes appear to have exchanged material during meiosis.

第40页：Chiasma formation is responsible for generating

Figure 1.23 Chiasma formation is responsible for generating recombinants.

第41页：Recombination involves pairing

Figure 1.24 Recombination involves pairing between complementary strands of the two parental duplex DNAs.

第42页：Denatured single strands of DNA can renature

Figure 1.13 Denatured single strands of DNA can renature to give the duplex form.

第43页：Key terms: Codon, Genetic, Initiation codon

Codon

Codon is a triplet of nucleotides that represents an amino acid or a termination signal.

Genetic

Genetic code is the correspondence between triplets in DNA (or RNA) and amino acids in protein.

Initiation codon

Initiation codon is a special codon (usually AUG) used to start synthesis of a protein.

ORF

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)

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 accept able substitute for the original meaning.

Termination codon

Termination codon is one of three (UAG, UAA, UGA) that causes protein synthesis to terminate.

Frame shift mutation results from an insertion or deletion that changes the phase of triplets, so that all codons are misread after the site of mutation.

第44页：Frame shift mutations show

Figure 1.25 Frame shift mutations show that the genetic code is read in triplets from a fixed starting point.

第45页：An open reading frame starts with AUG

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.

第46页：Key terms: Coding region, Leaderof a protein, RNA

Coding region

Coding region is a part of the gene that represents a protein sequence.

Leaderof a protein

Leaderof a protein is a short N-terminal sequence responsible for passage into or through a membrane.

RNA splicing

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

Trailer is a nontranslated sequence at the 3´end of an mRNA following the termination codon.

Transcription

Transcription is synthesis of RNA on a DNA template.

Translation

Translation is synthesis of protein on the mRNA template.

第47页：The recombination map of the tryptophan

Figure 1.27 The recombination map of the tryptophan synthetase gene corresponds with the amino acid sequence of the protein.

第48页：RNA is synthesized by using one strand of DNA

Figure 1.28 RNA is synthesized by using one strand of DNA as a template for complementary base pairing.

第49页：The gene may be longer than the sequence coding

Figure 1.29 The gene may be longer than the sequence coding for protein.

第50页：Gene expression is a multistage process

Figure 1.30 Gene expression is a multistage process.

第51页：Interrupted genes are expressed via a precursor

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.

第52页：Eukaryotic mRNA is modified by addition of a cap

Figure 5.16 Eukaryotic mRNA is modified by addition of a cap to the 5′end and poly(A) to the 3′end.

第53页：Key terms: cis-configur at ion, Trans-configur

cis-configur at ion

cis-configur at ion describes two sites on the same molecule of DNA.

Trans-configur at ion of two sites

Trans-configur at ion of two sites refers to their presence on two different molecules of DNA (chromosomes).

第54页：The cistron is defined by the complement-ati

Figure 1.20 The cistron is defined by the complement-ati on test. Genes are represented by bars; red stars identify sites of mutation.

第55页：Control sites in DNA provide binding sites

Figure 1.31 Control sites in DNA provide binding sites for proteins; coding regions are expressed via the synthesis of RNA.

第56页：A cis-acting site controls the adjacent DNA but

Figure 1.32 A cis-acting site controls the adjacent DNA but does not influence the other allele.

第57页：A trans-acting mutation in a protein affects

Figure 1.33 A trans-acting mutation in a protein affects both alleles of a gene that it controls.

第58页：Key terms: Central dogm a, Prion, Reverse

Central dogm a

Central dogm a describes the basic nature of genetic information: sequences of nucleic acid can be perpetuated and interconverted by replication, transcription, and reverse transcription, but translation from nucleic acid to protein is unidirectional, because nucleic acid sequences cannot be retrieved from protein sequences.

Prion

Prion is a proteinaceous infectious agent, which behaves as an inheritable trait, although it contains no nucleic acid. Examples are PrPSc, the agent of scrapie in sheep and bovine spongiform encephalopathy, and Psi, which confers an inherited state in yeast.

Reverse transcription

Reverse transcription is synthesis of DNA on a template of RNA; accomplished by reverse transcriptase enzyme.

Scrapie

Scrapie is a infective agent made of protein.

Virion

Virion is the physical virus particle (irrespective of its ability to infect cells and reproduce).

Viroid

Viroid is a small infectious nucleic acid that does not have a protein coat.

第59页：The central dogma states

Figure 1.34 The central dogma states that information in nucleic acid can be perpetuated or transferred, but the transfer of information into protein is irreversible.

第60页：Double-stranded and single-stranded nucleic acids

Figure 1.35 Double-stranded and single-stranded nucleic acids both replicate by synthesis of complementary strands governed by the rules of base pairing.

第61页：The amount of nucleic acid in the genome varies

Figure 1.36 The amount of nucleic acid in the genome varies over an enormous range.

第62页：PSTV RNA is a circular molecule

Figure 1.37 PSTV RNA is a circular molecule that forms an extensive double-stranded structure, interrupted by many interior loops. The severe and mild forms differ at three sites.

第63页：1. Two classic experiments proved

1. Two classic experiments proved that DNA is the genetic material. 2. DNA is a double helix consisting of antiparallel strands in which the nucleotide units are linked by 53 phosphodiester bonds. 3. A stretch of DNA may code for protein.4. A chromosome consists of an uninterrupted length of duplex DNA that contains many genes. 5. A gene may have multiple alleles. Recessive alleles are caused by a loss-of-functi on.

第64页：6. A mutation consists of a change in

6. A mutation consists of a change in the sequence of A·T and G·C base pairs in DNA.7. The natural incidence of mutations is increased by mutagens. 8. Forward mutations occur at a rate of ~106 per locus per gener at ion; back mutations are rarer. 9. Although all genetic information in cells is carried by DNA, viruses have genomes of double-stranded or single-stranded DNA or RNA.