1. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 14-1 Powerpoint to accompany Genetics: From Genes to Genomes Third Edition Hartwell ● Hood ● Goldberg ● Reynolds ● Silver ● Veres Chapter 14 Prepared by Malcolm Schug University of North Carolina Greensboro

2. 14-2 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Chromosomal Rearrangements and Changes in Chromosome Number Reshape Eukaryotic Genomes

3. 14-3 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Outline of Chapter 14 Rearrangements of DNA sequences within and between chromosomes Rearrangements of DNA sequences within and between chromosomes Deletions Deletions Duplications Duplications Inversions Inversions Translocations Translocations Movements of transposable elements Movements of transposable elements Changes in chromosome number Changes in chromosome number Aneuploidy: monosomy and trisomy Aneuploidy: monosomy and trisomy Monoploidy Monoploidy Polyploidy Polyploidy

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5. 14-5 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

6. 14-6 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Deletions remove genetic material from genome. Fig. 14.2

7. 14-7 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Phenotypic consequences of heterozygosity Homozygosity for deletion is often but not always lethal. Homozygosity for deletion is often but not always lethal. Heterozygosity for deletion is often detrimental. Heterozygosity for deletion is often detrimental. Fig. 14.3

8. 14-8 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Deletion heterozygotes affect mapping distances. Recombination between homologues can only occur if both carry copies of the gene. Recombination between homologues can only occur if both carry copies of the gene. Deletion loop formed if heterozygous for deletion Deletion loop formed if heterozygous for deletion Identification of deletion location on chromosome Identification of deletion location on chromosome Genes within can not be separated by recombination. Genes within can not be separated by recombination. Fig. 14.4 a

9. 14-9 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Deletions in heterozygotes can uncover genes. Pseudodominance shows a deletion has removed a particular gene. Pseudodominance shows a deletion has removed a particular gene. Fig. 14.5

10. 14-10 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Polytene chromosomes in Drosophila salivary glands can be used to map deletions. Interphase chromosomes replicate 10 times. Interphase chromosomes replicate 10 times. Each chromosome consists of 210 (1024) double helices. Each chromosome consists of 210 (1024) double helices. Reproducible bands provide detailed physical guide to gene mapping. Reproducible bands provide detailed physical guide to gene mapping. Total of about 5000 bands ranging from 3kb to 150kb Total of about 5000 bands ranging from 3kb to 150kb

11. 14-11 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Deletion heterozygotes form visible deletion loops in Drosophila polytene chromosomes.

12. 14-12 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Deletions can be used to locate genes. Deletions to assign genes to bands on Drosophila polytene chromosomes Deletions to assign genes to bands on Drosophila polytene chromosomes Complementation tests crossing deletion mutants with mutant genes of interests Complementation tests crossing deletion mutants with mutant genes of interests Deletion heterozygote reveals chromosomal location of mutant gene. Deletion heterozygote reveals chromosomal location of mutant gene. Fig. 14.8

13. 14-13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display In situ hybridization is a tool for locating genes on chromosomes. A probe containing the white gene hybridizes to the tip of the wild-type X chromosome of Drosophila. A probe containing the white gene hybridizes to the tip of the wild-type X chromosome of Drosophila.

14. 14-14 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Deletions to locate genes at the molecular level Labeled probe hybridizes to wild-type chromosome but not to deletion chromosome. Fig. 14.9 b

15. 14-15 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Metaphase cell hybridizes with the probe for DiGeorge syndrome caused by a microdeletion on chromosome 22. Green signal is an internal control at 22q13. Green signal is an internal control at 22q13. Red signal is at DiGeorge region at 22q11.2. Red signal is at DiGeorge region at 22q11.2.

16. 14-16 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Duplications add material to the genome. Fig. 14.11 a,b

17. 14-17 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Duplication loops form when chromosomes pair in duplication heterozygotes. In prophase I, the duplication loop can assume different configurations that maximize the pairing of related regions. Fig. 14.11 c

18. 14-18 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Duplications can affect phenotype. Novel phenotypes Novel phenotypes More gene copies More gene copies Genes next to duplication displaced to new environment altering expression Genes next to duplication displaced to new environment altering expression Fig. 14.12

19. 14-19 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Unequal crossing over between duplications increases or decreases gene copy number. Fig. 14.13

20. 14-20 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Summary of duplication and deletion affect on phenotype Alter number of genes on a chromosome and may affect phenotype of heterozygote Alter number of genes on a chromosome and may affect phenotype of heterozygote Heterozygosity creates one or three gene copies and creates imbalance in gene product altering phenotypes (some lethal). Heterozygosity creates one or three gene copies and creates imbalance in gene product altering phenotypes (some lethal). Genes may be placed in new location that modifies its expression. Genes may be placed in new location that modifies its expression. Deletions and duplications drive evolution by generating families of tandemly repeated genes. Deletions and duplications drive evolution by generating families of tandemly repeated genes.

21. 14-21 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Inversions reorganize the DNA sequence of a chromosome. Produced by half rotation of chromosomal regions after double-stranded break Produced by half rotation of chromosomal regions after double-stranded break Also rare crossover between related genes in opposite orientation or transposition Also rare crossover between related genes in opposite orientation or transposition Fig. 14.14a,b

22. 14-22 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display An inversion can affect phenotype if it disrupts a gene. Fig. 14.14 c

23. 14-23 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Inversion heterozygotes reduce the number of recombinant progeny. Inversion loop in heterozygote forms tightest possible alignment of homologous regions. Inversion loop in heterozygote forms tightest possible alignment of homologous regions. Fig. 14.15

24. 14-24 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Gametes produced from pericentric and paracentric inversions are imbalanced. Fig. 14.16

25. 14-25 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Pericentric inversion Paracentric inversion (cont’d) (cont’d) Fig. 14.16 cont’d

26. 14-26 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Inversions suppress recombination. Balancer chromosomes carry both a dominant marker D and inversions (brackets) that prevent recombination with experimental chromosome. Balancer chromosomes carry both a dominant marker D and inversions (brackets) that prevent recombination with experimental chromosome. Heterozygous parent will transmit balancer or experimental chromosome. Heterozygous parent will transmit balancer or experimental chromosome. Dominant mutation has an easily distinguished phenotype (e.g., curly wing). Dominant mutation has an easily distinguished phenotype (e.g., curly wing).

27. 14-27 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Translocations attach one part of a chromosome to another. Translocation – part of one chromosome becomes attached to nonhomologous chromosome Translocation – part of one chromosome becomes attached to nonhomologous chromosome Reciprocal translocation – two different parts of chromosomes switch places Reciprocal translocation – two different parts of chromosomes switch places Fig. 14.18 a

28. 14-28 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Robertsonian translocations can reshape genomes. Reciprocal exchange between acrocentric chromosomes generate large metacentric chromosome and small chromosome. Reciprocal exchange between acrocentric chromosomes generate large metacentric chromosome and small chromosome. Tiny chromosome may be lost from organism. Tiny chromosome may be lost from organism. Fig. 14.19

29. 14-29 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Leukemia patients have too many blood cells. Fig. 14.20

30. 14-30 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Heterozygosity for translocations diminishes fertility and results in pseudolinkage. Fig. 14.21 a.b

31. 14-31 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Three possible segregation patterns in a translocation heterozygote from the cruciform configuration Pseudolinkage – because only alternate segregation patterns produce viable progeny, genes near breakpoints act as if linked Fig. 14.21 c

32. 14-32 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Semisterility results from translocation heterozygotes. Semisterility results from translocation heterozygotes. < 50% of gametes arise from alternate segregation and are viable. < 50% of gametes arise from alternate segregation and are viable. Fig. 14.21 d

33. 14-33 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Translocation Down syndrome Translocation of chromosome 21 is small and thus produces viable gamete, but with phenotypic consequence. Fig. 14.22

34. 14-34 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Transposable elements move from place to place in the genome. 1930s Marcus Rhoades and 1950s Barbara McClintock – transposable elements in corn 1930s Marcus Rhoades and 1950s Barbara McClintock – transposable elements in corn 1983 McClintock received Nobel Prize 1983 McClintock received Nobel Prize Found in all organisms Found in all organisms Any segment of DNA that involves ability to move from one place to another in genome Any segment of DNA that involves ability to move from one place to another in genome Selfish DNA carrying only information to self-perpetuate Selfish DNA carrying only information to self-perpetuate Most 50 – 10,000 bp Most 50 – 10,000 bp May be present hundreds of time in a genome May be present hundreds of time in a genome LINES, long interspersed element in mammals LINES, long interspersed element in mammals ~ 20,000 copies in human genome up to 6.4kb in length ~ 20,000 copies in human genome up to 6.4kb in length SINES, short interspersed elements in mammals SINES, short interspersed elements in mammals ~ 300,000 copies in human genome ~ 300,000 copies in human genome ~ 7% of genome are LINES and SINES. ~ 7% of genome are LINES and SINES.

35. 14-35 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Retroposons generate an RNA that encodes a reverse transcriptase like enzyme. Two types Two types Poly-A tail at 3’ end of RNA-like DNA strand Poly-A tail at 3’ end of RNA-like DNA strand Long terminal repeat (LTRs) oriented in same direction on either end of element Long terminal repeat (LTRs) oriented in same direction on either end of element Fig. 14.26 a

36. 14-36 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 14.26 b

37. 14-37 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display The process of LTR transposition Fig. 14.26 c

38. 14-38 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Transposons encode transposase enzymes that catalyze events of transposition. Fig. 14.27 a

39. 14-39 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display P elements in Drosophila After excision of P element transposon, DNA exonucleases first widen gap and then repair it. After excision of P element transposon, DNA exonucleases first widen gap and then repair it. Repair uses sister chromatid or homologous chromosome as a template. Repair uses sister chromatid or homologous chromosome as a template. P strains of Drosophila have many copies of P elements. P strains of Drosophila have many copies of P elements. M strains have no copies. M strains have no copies. Hybrid dysgenesis – defects including sterility, mutation, and chromosomal breakage from cross between P and M strains Hybrid dysgenesis – defects including sterility, mutation, and chromosomal breakage from cross between P and M strains Promotes movement of P elements to new positions Promotes movement of P elements to new positions

40. 14-40 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Figure 14.27 b

41. 14-41 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Genomes often contain defective copies of transposable elements. Many TEs sustain deletions during transposition or repair. Many TEs sustain deletions during transposition or repair. If promoter needed for transcription deleted, TE can not transpose again If promoter needed for transcription deleted, TE can not transpose again Most SINES and LINES in human genome are defective TEs. Most SINES and LINES in human genome are defective TEs. Nonautonomous elements – need activity of non- deleted copies of same TE for movement Nonautonomous elements – need activity of non- deleted copies of same TE for movement Autonomous elements – move by themselves Autonomous elements – move by themselves

42. 14-42 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display TEs can generate mutations in adjacent genes spontaneous mutations in white gene of Drosophila Fig. 14.28

43. 14-43 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display TEs can generate chromosomal rearrangements and relocate genes. Fig. 14.29

44. 14-44 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display The loss or gain of one or more chromosomes results in aneuploidy.

45. 14-45 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Chromosomal rearrangements reshape the genome and contribute to evolution. Different sets of Robertsonian translocations between house mouse populations on the island of Madeira that produce sterile hybrids Different sets of Robertsonian translocations between house mouse populations on the island of Madeira that produce sterile hybrids Populations are close to becoming two species after colonizing the island only 600 years ago. Populations are close to becoming two species after colonizing the island only 600 years ago.

46. 14-46 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Autosomal aneuploidy is harmful to the organism. Monosomy usually lethal Monosomy usually lethal Trisomies – highly deleterious Trisomies – highly deleterious Trisomy 18 – Edwards syndrome Trisomy 18 – Edwards syndrome Trisomy 13 – Patau syndrome Trisomy 13 – Patau syndrome Trisomy 21 – Down syndrome Trisomy 21 – Down syndrome

47. 14-47 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Humans tolerate X chromosome aneuploidy because X inactivation compensates for dosage. Fig. 14.31

48. 14-48 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Mitotic nondisjunction Mitotic nondisjunction Failure of two sister chromatids to separate during mitotic anaphase Failure of two sister chromatids to separate during mitotic anaphase Generates reciprocal trisomic and monosomic daughter cells Generates reciprocal trisomic and monosomic daughter cells Chromosome loss Chromosome loss Produces one monosomic and one diploid daughter cell Produces one monosomic and one diploid daughter cell Fig. 14.32a

49. 14-49 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Mosaics – aneuploid and normal tissues that lie side-by-side Mosaics – aneuploid and normal tissues that lie side-by-side Aneuploids give rise to aneuploid clones. Aneuploids give rise to aneuploid clones. Fig. 14.32 b

50. 14-50 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Gynandromorph in Drosophila results from female losing one X chromosome during first mitotic division after fertilization. Fig. 14.33

51. 14-51 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Euploid individuals contain only complete sets of chromosomes.

52. 14-52 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Monoploid organisms contain a single copy of each chromosome and are usually infertile. Monoploid plants have many uses: Monoploid plants have many uses: Visualize recessive traits directly Visualize recessive traits directly Introduction of mutations into individual cells Introduction of mutations into individual cells Select for desirable phenotpyes (herbicide resistance) Select for desirable phenotpyes (herbicide resistance) Hormone treatment to grow selected cells Hormone treatment to grow selected cells

53. 14-53 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 14.34 a-b

54. 14-54 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Treatment with colchicine converts back to diploid plants that express desired phenotypes. Fig. 14.34 c

55. 14-55 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Polyploidy has accompanied the evolution of many cultivated plants. 1:3 of flowering plants are polyploid. 1:3 of flowering plants are polyploid. Polyploid often increases size and vigor. Polyploid often increases size and vigor. Often selected for agricultural cultivation Often selected for agricultural cultivation Tetraploids - alfalfa, coffee, peanuts Tetraploids - alfalfa, coffee, peanuts Octaploid - strawberries Octaploid - strawberries Fig. 14.35

56. 14-56 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Triploids are almost always sterile. Triploids are almost always sterile. Result from union of monoploid and diploid gametes Result from union of monoploid and diploid gametes Meiosis produces unbalanced gametes. Meiosis produces unbalanced gametes. Fig. 14.36

57. 14-57 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Tetraploids are often source of new species. Tetraploids are often source of new species. Failure of chromosomes to separate into two daughter cells during mitosis in diploid Failure of chromosomes to separate into two daughter cells during mitosis in diploid Cross between tetraploid and diploid creates triploids – new species, autopolyploids. Cross between tetraploid and diploid creates triploids – new species, autopolyploids. 14.37 a

58. 14-58 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Maintenance of tetraploid species depends on the production of gametes with balanced sets of chromosomes. Maintenance of tetraploid species depends on the production of gametes with balanced sets of chromosomes. Bivalents- pairs of synapsed homologous chromosomes that ensure balanced gametes Bivalents- pairs of synapsed homologous chromosomes that ensure balanced gametes Fig. 14.37 b

59. 14-59 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 14.37 c

60. 14-60 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Some polyploids have agriculturally desirable traits derived from two species. Amphidiploids created by chromosome doubling in germ cells Amphidiploids created by chromosome doubling in germ cells e.g., wheat – cross between tetraploid wheat and diploid rye produce hybrids with desirable traits e.g., wheat – cross between tetraploid wheat and diploid rye produce hybrids with desirable traits Fig. 14.38