教程讲稿遗传学and function of a gene

1、Chapter 7 Anatomy and Function of a Gene: Dissection Through Mutation Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-1 Outline of Chapter 7 What mutations are ? How often mutations occur ? What events cause mutations ? How mutations affect survival and evol

2、ution ? Mutations and gene structure ? Experiments using mutations demonstrate a gene is a ? discrete region of DNA. Mutations and gene function ? Genes encode proteins by directing assembly of amino ? acids Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-2

3、What are mutations? Mutations are heritable changes in DNA ? sequences. Forward mutation changes wild - type to a ? different allele Reverse mutation (reversion) causes mutation to ? revert back to wild - type Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-

4、3 Classification of mutations by their effect on DNA Substitution one nitrogenous base is replaced by one ? of the other three bases. Deletion block of one or more DNA pairs is lost. ? Insertion block of one or more DNA pairs is added. ? Inversion 180 ? rotation of a DNA segment. ? Reciprocal transl

5、ocation parts of nonhomologous ? chromosomes change places. Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-4 A Purines G Pyrimidines C T Purines A T Pyrimidines T A Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-5

6、Fig. 7.2 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-6 Fig. 7.2 Mutation rates from wild-type to recessive alleles for five coat color genes in mice Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-7 Fig. 7.3 Gene

7、ral observations of mutation rates Mutations affecting phenotype occur very ? rarely. The mutation rate varies from gene to gene. ? Ranges from less than 10 - 9 to more than 10 - 3 per gene per ? gamete The average rate is 2 - 12 ? 10 - 6 ? The average rate in bacteria is 10 - 8 to 10 - 7 ? The rate

8、 of forward mutation is almost always ? higher than the rate of reverse mutation. Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-8 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-9 Luria - Delbr ck fluctuation test

9、In 1943, Salvador Luria ? and Max Delbr ck . To examine the origin of ? bacterial resistance to bacteriophage . Cold Spring Harbor Laboratory, 1940s Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-10 Fig. 7.4 Copyright ? The McGraw-Hill Companies, Inc. Permi

10、ssion required to reproduce or display 7-11 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-12 Replica plating verifies preexisting mutations Fig. 7.5 a Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-13 Fig. 7.5b Co

11、pyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-14 Interpretation of Luria - Delbr ck fluctuation test and replica plating Mutations do not arise in particular genes as a direct ? response to environmental change. Mutations occur randomly at any time. ? Bacter

12、ial resistance arises from mutations that exist ? before exposure to bacteriocide . After exposure to bacteriocide , the bacteriocide ? es a selective agent killing off nonresistant cells, allowing only the preexisting resistant cells to survive. Copyright ? The McGraw-Hill Companies, Inc. Permissio

13、n required to reproduce or display 7-15 Where do mutations come from? Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-16 Deamination removes NH2 ? Hydrolysis of a purine ? base, A or G occurs group. Can change C to U, inducing a substitution of C - G 1000 ti

14、mes an hour in every human cell. to T - A after replication Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-17 Fig. 7.6 a,b UV light produces ? thymine dimers . X rays break the DNA backbone. ? Copyright ? The McGraw-Hill Companies, Inc. Permission required

15、to reproduce or display 7-18 Fig. 7.6 c, d Oxidation from free radicals formed by irradiation damages individual bases Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-19 Fig. 7.6 e Mistakes during replication alter genetic information 10 - 6 error rate for D

16、NA polymerase in vitro . ? With efficient DNA mismatch repair, errors during ? replication in the cells are exceedingly rare, less than once in 10 9 base pairs. Proofreading enzymes correct errors made during ? replication. DNA polymerase has 3 - to - 5 exonuclease activity which ? recognizes mismat

17、ched bases and excises it. In bacteria, methyl - directed mismatch repair finds errors ? on newly synthesized strands and corrects them. Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-20 Unequal crossing over creates one homologous chromosome with a duplica

18、tion and the other with a deletion Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-21 7.8 a Transposable elements move around the genome and are not susceptible to excision or mismatch repair Fig. 7.8 b Copyright ? The McGraw-Hill Companies, Inc. Permission

19、required to reproduce or display 7-22 The instability of certain trinucleotide repeats causes mutations Huntington disease : expansion of CAG repeats in the ? HD gene. Fragile X syndrome : expansion of CGG repeats in ? FMR - 1 gene. Genetics and Society Fig. B(1) Copyright ? The McGraw-Hill Companie

20、s, Inc. Permission required to reproduce or display 7-23 Fragile X Syndrome Moderate to severe mental retardation, second only to Down ? syndrome. Affects about one in 4,000 males and one in 8,000 females. ? Normal FMR patient X chromosome X chromosome Genetics and Society Copyright ? The McGraw-Hil

21、l Companies, Inc. Permission required to reproduce or display 7-24 Fig. A, B(2) Mutagens induce mutations H. J. Muller first discovered that X rays increase ? mutation rate in fruitflies . Exposed male Drosophila to large doses of X rays. ? Mated males to females with balancer X chromosome. ? (domin

22、ant Bar eyed mutation and multiple inversions) Could assay more than 1000 genes at once on the X ? chromosome. Mutagen: any physical or chemical agent that raises ? the frequency of mutations above the spontaneous rate. Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or

23、display 7-25 Muller s experiment Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-26 Fig. 7.9 Mutagens alter DNA using different mechanisms Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-27 Fig. 7.10 a Fig. 7.10 b Co

24、pyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-28 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-29 Fig. 7.10 b Fig. 7.10 b Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-30

25、 Fig. 7.10 c Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-31 Consequences of mutations Germ line mutations passed on to next ? generation and affect the evolution of species. Somatic mutations affect the survival of an ? individual. Cell cycle mutations m

26、ay lead to cancer. ? Because of potential harmful affects of ? mutagens to individuals, tests have been developed to identify carcinogens. Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-32 The Ames test Developed by Bruce Ames. ? Used to determine if a chem

27、ical is a mutagen. ? Examine if a chemical can induce his + ? revertants of his - mutants of Salmonella typhimurium . Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-33 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7

28、-34 DNA Damage Repair Light repair: photoreactivation or ? photorepair Excision repair: removal of damaged bases or ? nucleotides Methyl-directed mismatch repair: corrects ? errors in DNA replication binational repair ? SOS repair: error-prone ? Copyright ? The McGraw-Hill Companies, Inc. Permission

29、 required to reproduce or display 7-35 Light repair Photolyase enzyme to remove thymine dimers. Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-36 Base Excision Repair Important for the removal of uracil caused by cytosine deamination. Fig. 7.11 Copyright ?

30、The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-37 Nucleotide Excision Repair Fig. 7.12 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-38 Methyl - directed mismatch repair Fig. 7.13 Copyright ? The McGraw-Hill Companies, Inc. P

31、ermission required to reproduce or display 7-39 Xeroderma pigmentosum First described in 1874 by Hebra and Kaposi. ? A rare disorder transmitted in an autosomal recessive manner. ? Symptoms include dry and pigmented skin, photosensitivity, ? premature skin aging, and malignant tumor development. Due

32、 to hypersensitivity to ultraviolet (UV) radiation resulting ? from the lack of a key enzyme in nucleotide excision repair system. Fig. 7.15 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-40 What mutations tell us about gene structure ? Copyright ? The McGr

33、aw-Hill Companies, Inc. Permission required to reproduce or display 7-41 Complementation testing Complementation group : A collection of mutations that do not complement each other. Complementation testing tells us whether two mutations ? are in the same or different genes. Copyright ? The McGraw-Hi

34、ll Companies, Inc. Permission required to reproduce or display 7-42 Fig. 7.18 a Five complementation groups (genes) for eye color. bination mapping demonstrates distance between genes and alleles. Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-43 Fig. 7.18

35、b,c A gene is a linear sequence of nucleotide pairs Seymour Benzer , late 1950s. ? If a gene is a linear set of nucleotides, ? bination between homologous chromosomes carrying different mutations within the same gene should generate a wild - type allele. Worked on T4 bacteriophage rII - mutants. ? C

36、opyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-44 bination within a gene could generate a wild - type allele Fig. 7.19 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-45 Fine structure map of rII gene region Fig. 7.2

37、1 c Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-46 Benzer s experiments demonstrate that a ? gene is a linear sequence of nucleotide pairs that mutate independently and bine with each other. Some regions of chromosomes mutate at a ? higher rate than othe

38、rs hot spots . Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-47 What mutations tell us about gene function ? Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-48 The One Gene, One Enzyme Hypothesis George Beadle and

39、Edward Tatum, 1940s. ? Isolated mutagen induced mutants that disrupted ? synthesis of arginine , an amino acid required for Neurospora growth. Prototroph wild - type that needs no supplement; can ? synthesize all required growth factors. Auxotroph needs supplement to grow on minimal media. ? Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-49 Neurospora crassa Life Cycle Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 7-50 Fig. 5.14 b Fig. 7.23 a Copyright ? The McGraw-Hill Companies, Inc. Permission required