Chapter 14 Chromosomal Rearrangements and Changes in Chromosome Number Reshape Eukaryotic Genomes

1. Chapter 14Chromosomal Rearrangements and Changes in Chromosome Number Reshape Eukaryotic Genomes

2. Outline of Chapter 14 • Rearrangements of DNA sequences within and between chromosomes • Deletions • Duplications • Inversions • Translocations • Movements of transposable elements • Changes in chromosome number • Aneuploidy: monosomy and trisomy • Monoploidy • Polyploidy

4. Deletions remove genetic material from genome Fig. 13.2

5. Phenotypic consequences of heterozygosity • Homozygosity for deletion is often but not always lethal • Heterozygosity for deletion is often detrimental Fig. 13.3

6. Deletion heterozygotes affect mapping distances • Recombination between homologues can only occur if both carry copies of the gene • Deletion loop formed if heterozygous for deletion • Identification of deletion location on chromosome • Genes within can not be separated by recombination Fig. 13.4 a

7. Deletion loops in polytene chromosomes Fig. 13.4 b

8. Deletions in heterozygotes can uncover genes • Pseudodominance shows a deletion has removed a particular gene Fig. 13.5

9. Deletions can be used to locate genes • Deletions to assign genes to bands on Drosophila polytene chromosomes Complementation tests crossing deletion mutants with mutant genes of interests • Deletion heterozygote reveals chromosomal location of mutant gene Fig. 13.6

10. Deletions to locate genes at the molecular level • Labeled probe hybridizes to wild-type chromosome but not to deletion chromosome Fig. 13.7 a

11. Molecular mapping of deletion breakpoints by Southern blotting Fig. 13.7 b, c

12. Duplications add material to the genome Fig. 13.8 a,b

13. 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. 13.8 c

14. Duplications can affect phenotype • Novel phenotypes • More gene copies • Genes next to duplication displaced to new environment altering expression Fig. 13.9

15. Unequal crossing over between duplications increases or decreases gene copy number Fig. 13.10

16. Fig. 13.10

17. Summary of duplication and deletion effects on phenotpye • Alter number of genes on a chromosome and may affect phenotype of heterozygote • Heterozygosity create one or three gene copies and create imbalance in gene product altering phenotypes (some lethal) • Genes may be placed in new location that modifies its expression • Deletions and duplications drive evolution by generating families of tandemly repeated genes

18. Inversions reorganize the DNA sequence of a chromosome • Produced by half rotation of chromosomal regions after double-stranded break • Also rare crossover between related genes in opposite orientation or transposition Fig. 13.11a,b

19. An inversion can affect phenotype if it disrupts a gene Fig. 13.11 c

20. Inversion heterozygotes reduce the number of recombinant progeny • Inversion loop in heterozygote forms tightest possible alignment of homologous regions Fig. 13.12

21. Gametes produced from pericentric and paracentric inversions are imbalanced Fig. 13.13

22. Pericentric inversion Paracentric inversion (cont’d) (cont’d) Fig. 13.13 cont’d

23. Inversions suppress recombination • 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. • Dominant mutation has an easily distinguished phenotpye (e.g., curly wing)

24. Translocations attach on part of a chromosome to another • Translocation – part of one chromosome becomes attached to nonhomologous chromosome • Reciprocal translocation – two different parts of chromosomes switch places Fig. 13.15 a

25. Robertsonian translocations can reshape genomes • Reciprocal exchange between acrocentric chromosomes generate large metacentric chromosome and small chromosome • Tiny chromosome may be lost from organism Fig. 13.16

26. Leukemia patients have too many blood cells Fig. 13.17

27. Heterozygosity for translocations diminishes fertility and results in pseudolinkage Fig. 13.18 a.b

28. Three possible segregation patterns in a translocation heterozygote from the cruciform configuration Fig. 13.18 c Pseudolinkage – because only alternate segregation patterns produce viable progeny, genes near breakpoints act as if linked

29. Semisterility results from translocation heterozygotes • < 50% of gametes arise from alternate segregation and are viable Fig. 13.18 d

30. Translocation Down syndrometranslocation of chromosome 21 is small and thus produces viable gamete, but with phenotypic consequence Fig. 13.19

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

32. Retroposons generate an RNA that encodes a reverse transciptase like enzyme • Two types • Poly-A tail at 3’ end of RNA-like DNA strand • Long terminal repeat (LTRs) oriented in same direction on either end of element Fig. 13.23 a

33. Fig. 13.23 b

34. The process of LTR transposition Fig. 13.23

35. Transposons encode transposase enzymes that catalyze events of transposition Fig. 13.24 a

36. P elements in Drosophila • 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 • P strains of Drosophila have many copies of P elements • M strains have no copies • Hybrid dysgenesis – defects including sterility, mutation, and chromosomal breakage from cross between P and M strains • Promotes movement of P elements to new positions

38. Genomes often contain defective copies of transposable elements • Many TEs sustain deletions during transposition or repair • If promoter needed for transcription deleted, TE can not transpose again • Most SINES and LINES in human genome are defective TEs • Nonautonomous elements – need activity of nondeleted copies of same TE for movement • Autonomous elements – move by themselves

39. TEs can generate mutations in adjacent genesspontaneous mutations in white gene of Drosophila Fig. 13.25

40. TEs can generate chromosomal rearrangements and relocate genes Fig. 13.26

41. The loss or gain of one or more chromosomes results in aneuploidy

42. Autosomal aneuploidy is harmful to the organism • Monosomy usually lethal • Trisomies – highly deleterious • Trisomy 18 – Edwards syndrome • Trisomy 13 – Patau syndrome • Trisomy 21 – Down syndrome

43. Humans tolerate X chromosome aneuploidy because X inactivation compensates for dosage Fig. 13.27

44. Mitotic nondisjunction • Failure of two sister chromatids to separate during mitotic anaphase • Generates reciprocal trisomic and monosomic daughter cells • Chromosome loss • Produces one monosomic and one diploid daughter cell Fig. 13.28 a

45. Mosaics – aneuploid and normal tissues that lie side-by-side • Aneuploids give rise to aneuploid clones Fig. 13.28 b

46. Gynandromorph in Drosophila results from female losing one X chromosome during first mitotic division after fertilization Fig. 13.29

47. Euploid individuals contain only complete sets of chromosomes

48. Monoploid organisms contain a single copy of each chromosome and are usually infertile • Monoploid plants have many uses • Visualize recessive traits directly • Introduction of mutations into individual cells • Select for desirable phenotpyes (herbicide resistance) • Hormone treatment to grow selected cells

49. Fig. 13.30

50. Treatment with colchicine converts back to diploid plants that express desired phenotypes Fig. 13.30 c