讲义文稿遗传学chapter05linkage recombination and mappping of genes

1、Chapter 5 Linkage, Recombination, and the Mapping of Genes on Chromosomes 5-1 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Outline of Chapter 5 Genetic linkage and meiotic recombination ? Genes linked together on the same chromosome usually ? assort togethe

2、r. Linked genes may become separated through recombination. ? Genetic mapping ? The frequency with which genes become separated reflects ? the physical distance between them. Mitotic recombination ? Rarely, recombination occurs during mitosis. ? In eukaryotes mitotic recombination produces genetic ?

3、 mosaics. 5-2 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Independent assortment Genes on different chromosomes A a B b Gametes A a B B A a b b AB: Ab: aB: ab=1: 1: 1: 1 5-3 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or di

4、splay Genetic linkage Two genes on the same chromosome segregate together. A B a b Gametes A A B B a b a b AB: Ab: aB: ab=2: 0: 0: 2 5-4 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Genetic linkage and recombination on the X chromosome in Drosophila w + : b

5、rick-red eyes w : white eyes y + : brown body y : yellow body Y: Y chromosome Fig. 5.2 5-5 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 5.3 5-6 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Parental and recombi

6、nant classes are opposite of one another ? in these two crosses. Similar percentages of recombinant and parental types show ? that the frequency of recombination is independent of the arrangement of alleles. 5-7 Fig. 5.3 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or

7、 display For genes w and y : Recombinant frequency (RF) = Recombinant classes/Total classes 5-8 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Autosomal Genes Can Also Exhibit Linkage Linked genes are not inherited in a 9:3:3:1 ratio. ? Testcrosses with one p

8、arent homozygous for recessive ? alleles of both genes can help determine if linked. Parental class outnumbers recombinant class ? demonstrates linkage. 5-9 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display b + : brown body color b : black body color c + : strai

9、ght edges in wing c : curved edges in wing 5-10 Fig. 5.4 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Gene b and gene c are linked on the same chromosome b c + c b + Gametes c b + c b c + b + b c + Recombinant classes Parental classes 23% 77% 5-11 Copyright

10、 ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Reciprocal exchanges between homologous chromosomes during meiosis are the physical basis of recombination 1909 Frans Janssens observed chiasmata , regions ? in which nonsister chromatids of homologous chromosomes cross o

11、ver each other during prophase of the first meiotic division. Chiasmata T. H. Morgan suggested these were sites of ? chromosome breakage and exchange resulting in genetic recombination. 5-12 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Crossing - over leads

12、 to separation of linked genes A B B A x a b a b Gametes a b B Parental A Recombinant b A a B 5-13 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Experimental evidence of reciprocal chromosomal exchange in genetic recombination 1931 Genetic recombination depe

13、nds on the ? reciprocal exchange of parts between maternal and paternal chromosomes. Harriet Creighton and Barbara McClintock studied corn. ? Curtis Stern studied fruit flies. ? Physical markers to keep track of specific chromosome parts ? Genetic markers were points of reference to determine if ? p

14、articular progeny were result of recombination. 5-14 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Genetic recombination between car and Bar genes on the Drosophila X chromosome 5-15 Fig. 5.6 Copyright ? The McGraw-Hill Companies, Inc. Permission required to

15、 reproduce or display Chiasmata mark the sites of recombination Fig. 5.7 a-c 5-16 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 5.7 d-f 5-17 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Summary of linkage and r

16、ecombination In dihybrid crosses, departures from a 1:1:1:1 ? ratio of F1 gametes indicate that the two genes are linked on the same chromosome. A non - 2:0:0:2 segregation pattern of F2 ? progenies indicates genetic recombination. 5-18 Copyright ? The McGraw-Hill Companies, Inc. Permission required

17、 to reproduce or display Genes close together on the same chromosome are linked and ? do not segregate independently. Linked genes lead to a larger number of parental class than ? expected in double heterozygotes . Mechanism of recombination is crossing over. ? Chiasmata are the visible signs of cro

18、ssing over. ? The farther away genes are the greater the opportunity for ? chiasmata to form. Recombination frequencies reflect physical distance between ? genes. Recombination frequencies between two genes vary from 0% to ? 50%. Linkage is never 100%. No matter how tightly two genes are ? linked, y

19、ou will find some recombination if you observe enough individuals. 5-19 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 5-20 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Human colorblindness and two forms of hemophili

20、a are X-linked traits 5-21 Fig. 5.26 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Pedigrees of colorblindness and hemophilia inheritance Fig. 5.1 5-22 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Genetic mapping: L

21、ocating genes along a chromosome For two genes linked on one chromosome: The probability of separation during transmission ? increases when their distance increases. We can use data about how often genes separate to ? map their relative locations. 5-23 Copyright ? The McGraw-Hill Companies, Inc. Per

22、mission required to reproduce or display Recombination Frequencies for Pairs of Genes Reflect Distance Between Them Alfred H. Sturtevant proposed that percentage ? of recombination, or recombination frequency (RF) reflects the physical distance separating two genes. RF = Recombinant classes/Total cl

23、asses 5-24 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display 1 map unit ( m.u . ), or 1 centimorgan ( cM ) = 1% RF (1% recombinant progeny) Fig. 5.8 5-25 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Mapping Genes by Com

24、parisons of Two-point Crosses Fig. 5.9 5-26 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Limitations of two - point crosses Difficult to determine gene order if two genes ? lie very close. Actual distances between genes do not always ? add up. Pairwise cros

25、ses are time - and labor - ? consuming. 5-27 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Three - Point Crosses: A faster and more accurate method to map genes 5-28 Fig. 5.10 a Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or

26、display vg ? b RF=(252+241+131+118)x100/ 4197=17.7 m.u. vg ? pr RF=(252+241+13 +9) x100/ 4197=12.3 m.u. b ? pr RF=(131+118+13+ 9) x100/ 4197=6.4 m.u. 5-29 Fig. 5.10 a Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display vg ? b distance: 17.7 m.u. vg ? pr distance:

27、12.3 m.u. b ? pr distance: 6.4 m.u. Fig. 5.10 b 5-30 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Inferring the location of a crossover event Fig. 5.11 5-31 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display vg ? b dista

28、nce should be adjusted: RF=(252+241+13+9+131+118+13+9)x100/ 4197=18.7 m.u. Original calculation: RF=(252+241+131+118)x100/ 4197=17.7 m.u. Fig. 5.11 5-32 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display The predicted probability of the double crossovers: 12.3% (

29、vg ? pr) x 6.4% (b ? pr)=0.79% The actual probability of the double crossovers: (13+9) / 4197=0.52% Fig. 5.11 5-33 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Chromosomal interference: The phenomenon of chromosomal crossovers not occurring independently. C

30、oefficient of coincidence: The ratio between the actual frequency of double crossovers observed in an experiment and the number of crossovers expected on the basis of independent probabilities. For the three-point cross: 0.52% / 0.79%=0.66 5-34 Copyright ? The McGraw-Hill Companies, Inc. Permission

31、required to reproduce or display Summary of three - point cross analysis Cross true breeding mutant with wild - type. ? Analyze F2 individuals (males if sex linked). ? Parental class most frequent ? Double crossovers least frequent ? Determine order of genes based on parental and ? recombinant class

32、es. Determine genetic distance between each pair of ? recombinants. 5-35 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Genes chained together by linkage are known as linkage groups Fig. 5.13 A genetic map of 5-36 the fruit fly Copyright ? The McGraw-Hill Com

33、panies, Inc. Permission required to reproduce or display Are genetic maps and physical maps correlated? The order of genes in a genetic map is the same as the ? order of those same genes along the DNA molecule of a chromosome. The physical distance (amount of DNA separating ? genes) is not always th

34、e same as the genetic distance between genes. Factors responsible for differences in physical and genetic ? map distances: Double, triple, and even more crossovers ? 50% limit on recombination frequency observable in a cross ? Recombination frequency is not uniform across a chromosome. ? ? Recombina

35、tion hotspots ? Recombination deserts 5-37 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Tetrad Analysis in Fungi Model organisms for understanding the ? mechanism of recombination because all four haploid products of meiosis are contained in ascus . Ascospo

36、res within ascus germinate into ? haploid individuals. Saccharomyces cerevisiae the baker s yeast ? ? Neurospora crassa the bread mold 5-38 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Neurospora crassa Life Cycle 5-39 Fig. 5.14 b Copyright ? The McGraw-Hil

37、l Companies, Inc. Permission required to reproduce or display Saccharomyces cerevisiae Life Cycle Fig. 5.14 a 5-40 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Tetrads are generated from sporulation Diploid MAT a/ ? Starvation Ascus wall Haploid Tetrad 5-41

38、 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Tetrad Analysis Heterozygote (a/ ? bud3 ? :TRP1 /+) A tetrad Haploid (a BUD3 ) ( ? BUD3 ) (a bud3 ? :TRP1) ( ? bud3 ? :TRP1 ) 5-42 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or

39、display Tetrad Dissection Microscope 5-43 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Tetrads can be characterized by the number of parental and recombinant spores they contain. Fig. 5.15 a 5-44 Copyright ? The McGraw-Hill Companies, Inc. Permission requir

40、ed to reproduce or display Fig. 5.15 b,c 5-45 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display When PD=NPD, two genes are unlinked, or linked but lie far apart. Fig. 5.15 d,e 5-46 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or d

41、isplay When PD significantly outnumbers NPD, two genes are linked 5-47 Fig. 5.16 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display How crossovers between linked genes generate different tetrads ? Fig. 5.17 a-c 5-48 Copyright ? The McGraw-Hill Companies, Inc. Per

42、mission required to reproduce or display Fig. 5.17 d-f 5-49 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display How to calculate RF in tetrad analysis? RF = NPD + ? T ? 100 Total tetrads RF = (3+1/2 x 70)/200 X 100= 19 m.u. Fig. 5.16 5-50 Copyright ? The McGraw-Hi

43、ll Companies, Inc. Permission required to reproduce or display Crossover Occurs after Chromosome Replication Fig. 5.18 mod 5-51 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Mitotic recombination Discovered in 1936 by an early Drosophila geneticist, ? Curt S

44、tern. Recombination occurs during mitosis. ? Initiated by DNA breaks caused by replication errors ? or exposures to radiation. Rare events, less than 10 - 6 . ? 5-52 Copyright ? The McGraw-Hill Companies, Inc. Permission required to reproduce or display Twin spots in Drosophila Adjacent patches of tissue that differ both from each other and ? the surrounding tissue