variation in chromosome structure and number

1. 1 VARIATION IN CHROMOSOME STRUCTURE AND NUMBER Chapter 8

2. 2 GENETIC VARIATION Genetic variation Includes genetic differences between members of the same species Due to alterations of the genetic material �Mutations� Also includes genetic variation between members of different species

3. 3 GENETIC VARIATION Sources of genetic variation Single gene mutations Small changes occurring within a particular gene Chromosome mutations �Chromosomal aberrations� Substantial change in chromosome structure Genome mutations Change in chromosome number

4. 4 CHROMOSOME STRUCTURE The composition of a chromosome can be changed Can have major phenotypic effects on the organism Cause of several genetic diseases May appear normal, but have a high likelihood of producing offspring with genetic abnormalities Important force in the evolution of new species

5. 5 CHROMOSOME STRUCTURE Most members of the same species have very similar chromosomes Sex chromosomes often differ Humans have 46 chromosomes Drosophila have 8 chromosomes etc.

6. 6 CHROMOSOME STRUCTURE Chromosomes can vary considerably in size and shape Various features used for identification Size Centromere location Banding patterns

7. 7 CHROMOSOME STRUCTURE Centromere location differs between chromosomes At the middle in a metacentric chromosome Near the middle in a submetacentric chromosome Near an end in an acrocentric chromosome At an end in a telocentric chromosome

8. 8 CHROMOSOME STRUCTURE Centromere is never exactly in the center of a chromosome Short arm is designated �p� �Petite� Long arm is designated �q�

9. 9 CHROMOSOME STRUCTURE Chromosomes are lined up on a karyotype Short arms on top Numbered in descending order of size Chromosome 1 is the largest, etc. Sex chromosomes are an exception

10. 10 CHROMOSOME STRUCTURE Stained chromosomes produce characteristic banding patterns Several different staining procedures are used e.g., G banding with Giemsa dye Treatment with mild heat of proteolytic enzymes partially degrades chromosomal proteins Chromosomes are them exposed to Giemsa dye Some regions bind the dye heavily to produce a heavy band Other regions bind the dye poorly to produce a light band

11. 11 CHROMOSOME STRUCTURE Giemsa-stained chromosomes possess characteristic banding patterns ~300 G bands during metaphase ~2,000 G bands during prophase

12. 12 CHROMOSOME STRUCTURE Chromosome banding patterns are useful Individual chromosomes can be distinguished from each other Especially helpful if they have similar sizes and centromere locations Chromosomal rearrangements are more easily detected May reveal evolutionary relationships among chromosomes of closely related species

13. 13 CHROMOSOME STRUCTURE Chromosome structure can be altered in two primary ways Change in the total amount of genetic material within a chromosome Rearrangement of genetic material within a chromosome

14. 14 CHROMOSOME STRUCTURE Chromosomal rearrangements Deficiency (deletion) Duplication Inversion Translocation Simple Reciprocal

15. 15 CHROMOSOME STRUCTURE Chromosomal deficiency Often the result of chromosome breakage Chromosome breaks in one or more places Fragment without a centromere lost and degraded Terminal or interstitial deficiency

16. 16 CHROMOSOME STRUCTURE Chromosomal deficiency Can result from improper recombination Recombination at incorrect locations between homologous chromosomes Results in a duplication and a deficiency

17. 17 CHROMOSOME STRUCTURE Chromosomal deficiencies tend to be detrimental Consequences depend on size and genes involved Larger deletions tend to be more harmful Many examples of significant phenotypic influences e.g., Cri-du-chat syndrome, Angelman syndrome, Prader-Willi syndrome, various cancers, etc.

18. 18 CHROMOSOME STRUCTURE Chromosomal deficiency Cri-du-chat syndrome Deficiency in short arm of chromosome 5 Single copy of deficiency sufficient for an array of abnormalities Severe mental retardation Unique facial anomalies Unusual cat-like cry

19. 19 CHROMOSOME STRUCTURE Chromosomal deficiencies can be detected through a variety of techniques Cytological Genetic Molecular

20. 20 CHROMOSOME STRUCTURE Cytological detection of deficiencies Many deficiencies are large enough to be seen with a light microscope e.g., Cri-du-chat, Prader-Willi, etc. Fairly small deletions are often difficult to detect with simple microscopy In situ hybridization can aid in detection

21. 21 CHROMOSOME STRUCTURE Genetic detection of deficiencies Helpful when a mutation causes a phenotypic effect Alleles with deletions cannot revert back to wild-type through spontaneous mutations Requires large populations of experimental organisms Sometimes revealed through pseudodominance Allele opposite deletion is phenotypically expressed Individual is hemizygous for the recessive allele

22. 22 CHROMOSOME STRUCTURE Duplications result in extra genetic material Usually caused by abnormal events in recombination Crossing over generally occurs at analogous sites in homologous chromosomes Crossovers sometimes occur at misaligned sites Results in one chromosome with a deletion and one chromosome with a duplication

23. 23 CHROMOSOME STRUCTURE Gene duplications Generally happen as rare, sporadic events during the evolution of species Multiple copies of genes can evolve into a family of genes with specialized functions

24. 24 CHROMOSOME STRUCTURE Gene duplications Consequences tend to be correlated with size Small duplications are less likely to have harmful effects than comparable deletions Having one copy of a gene appears less harmful than having three copies

25. 25 CHROMOSOME STRUCTURE Relatively few well-defined syndromes result from gene duplications e.g., Charcot-Marie-Tooth disease Caused by a small duplication in the short arm of chromosome 17 Relatively common peripheral neuropathy Characterized by numbness in the hands and feet

26. 26 CHROMOSOME STRUCTURE Sabra Colby Tice (1914) Discovered a fly with a reduced number of facets in the eye �Bar eyes� X-linked trait Shows incomplete dominance

27. 27 CHROMOSOME STRUCTURE Charles Zeleny (1921) Identified rare mutants in a true-breeding stock of bar-eyed flies Flies had even fewer facets �Ultra-bar� (�double-bar�) Also displayed incomplete dominance

28. 28 CHROMOSOME STRUCTURE Calvin Bridges (1930s) Investigated the bar/ultra-bar phenomenon at the cytological level Viewed chromosomes in cells of the Drosophila salivary gland Replicate many times to form giant polytene chromosomes Banding pattern is easy to see in great detail Very small changes in chromosome structure can be detected Can even detect duplication or deletion of a single gene

29. 29 CHROMOSOME STRUCTURE Calvin Bridges (1930s) Hypothesis Cytological examination of polytene chromosomes may reveal information concerning the nature of the bar and ultra-bar phenotypes

30. 30 CHROMOSOME STRUCTURE Calvin Bridges (1930s) Starting materials True-breeding bar-eyed Drosophila strain True-breeding wild-type Drosophila strain

31. 31 CHROMOSOME STRUCTURE Calvin Bridges (1930s) Experimental design Identify rare mutants within the bar-eyed strain Ultra-bar mutants Wild-type revertants

32. 32 CHROMOSOME STRUCTURE Calvin Bridges (1930s) Experimental design Dissect salivary glands from larva of wild-type and bar-eyed strains Dissect salivary glands from larva of bar-revertant (wild-type) strain and ultra-bar mutant strain Stain, squash, and view the banding patterns of these polytene chromosomes

33. 33 CHROMOSOME STRUCTURE Calvin Bridges (1930s) The data Banding patterns correlate with phenotypes

34. 34 CHROMOSOME STRUCTURE Calvin Bridges (1930s) Interpreting the data The bar phenotype is caused by a gene duplication Region 16A of the X chromosome A misaligned crossover in this region produces both ultra-bar and bar-revertant alleles

35. 35 CHROMOSOME STRUCTURE Calvin Bridges (1930s) Interpreting the data Gene duplication and triplication are also associated with a phenomenon known as position effect A female bar homozygote has four copies of the gene A female ultra-bar heterozygote has four copies of the gene The ultra-bar heterozygote has fewer facets (45) than the bar homozygote (70) The positioning of the three copies next to each other increases the severity of the defect Caused by effects on the level of gene expression

36. 36 CHROMOSOME STRUCTURE Most small chromosomal duplications have no phenotypic effect Vitally important Provide raw material for the addition of more genes into a species� chromosomes Can lead to the formation of a gene family

37. 37 CHROMOSOME STRUCTURE Gene families Two or more genes that are similar to each other Derived from the same ancestral gene Over time, the two copies accumulate different mutations Genes remain similar, but not identical Multiple occurrences produce a family of many similar genes

38. 38 CHROMOSOME STRUCTURE Gene families Genes derived from a single ancestral gene are termed homologous Homologous genes within a single species are termed paralogues Constitute a gene family

39. 39 CHROMOSOME STRUCTURE Globin gene family Found in humans Also found in numerous related species Encode polypeptides that function in oxygen binding e.g., Hemoglobin polypeptides

40. 40 CHROMOSOME STRUCTURE Globin gene family Composed of 14 homologous genes Originally derived from a single ancestral globin gene

41. 41 CHROMOSOME STRUCTURE Globin gene family Ancestral globin gene first duplicated about 800 million years ago Subsequent duplication have produced a total of 14 genes on three different human chromosomes Gene families are important in the evolution of traits

42. 42 CHROMOSOME STRUCTURE Globin gene family All globin polypeptides are subunits of proteins playing a role in oxygen binding The accumulation of different mutations in the various family members has created globins specialized in their functions e.g., Myoglobin is better at binding and storing oxygen in muscle cells e.g., Hemoglobin is better at binding and transporting oxygen via the red blood cells

43. 43 CHROMOSOME STRUCTURE Globin gene family The accumulation of different mutations in the various family members has created globins specialized in their functions Different globing genes are expressed at different stages of human development Differences reflect the differences in oxygen transport needs during embryonic, fetal, and postpartum stages of life e-globin and z-globin are expressed in very early embryonic stages g-globin genes exhibit maximal expression during the second and third trimesters of gestation After birth, g-globin genes are turned off and the b-globin gene is turned on

44. 44 CHROMOSOME STRUCTURE Chromosomal inversion Contains a segment that has been flipped to the opposite orientation Pericentric inversions include the centromere within the inverted region The centromere lies outside of paracentric inversions

45. 45 CHROMOSOME STRUCTURE Chromosomal inversion The total amount of genetic material is unchanged Genes within the inverted region are generally transcribed correctly Most inversions have no phenotypic consequences

46. 46 CHROMOSOME STRUCTURE Chromosomal inversion Rare inversions can result in an altered phenotype Break points within genes can alter the function of the gene e.g., Hemophilia (type A) can be caused by an inversion disrupting the gene for factor VIII Inversion (or translocation) can reposition a gene in a way that alters its normal level of gene expression �Position effect�

47. 47 CHROMOSOME STRUCTURE Chromosomal inversions Surprisingly common ~2% of the human population carry inversions detectable with a light microscope Generally phenotypically normal Some produce offspring with genetic abnormalities

48. 48 CHROMOSOME STRUCTURE Inversion heterozygote Carries two different chromosomes in a set Carries one normal chromosome Carries one chromosome with an inversion Generally phenotypically normal High probability of producing gametes abnormal in their total genetic content With a large inversion, perhaps 1/3 or more of the gametes are abnormal Due to crossing over within the inverted region

49. 49 CHROMOSOME STRUCTURE Inversion heterozygote Pairs of homologous sister chromatids synapse with each other during meiosis I Inversion loop must form in inversion heterozygote Permits homologous genes on both chromosomes to align next to each other Crossovers with the inversion loop produce highly abnormal chromosomes

50. 50 CHROMOSOME STRUCTURE Pericentric inversion heterozygote Single crossover between sister chromatids within the inverted region Two abnormal chromosomes produced Both contain a deleted segment and a duplicated segment Phenotypic abnormalities in offspring likely These types of inversions can be important in the formation of new species

51. 51 CHROMOSOME STRUCTURE Paracentric inversion heterozygote Single crossover between sister chromatids within the inverted region Two abnormal chromosomes produced One possesses two centromeres �Dicentric chromosome� (with a dicentric bridge) Acentric fragment also produced Lacks a centromere

52. 52 CHROMOSOME STRUCTURE Paracentric inversion heterozygote Acentric fragment will be lost and degraded in subsequent cell divisions The dicentric chromosome may break within the dicentric bridge Occurs if the two centromeres move toward opposite poles Net result is two chromosomes with deletions

53. 53 CHROMOSOME STRUCTURE Translocations Chromosomal rearrangements A portion of a chromosome is attached to a non-homologous chromosome

54. 54 CHROMOSOME STRUCTURE Ends of normal chromosomes possess telomeres Contain specialized DNA repeat sequences Prevent attachment of chromosomal DNA to chromosome ends Some agents cause chromosomes to break Broken ends lack telomeres DNA repair enzymes may join them together Abnormal chromosomes are formed A translocation results

55. 55 CHROMOSOME STRUCTURE Translocations Can be formed by crossover between nonhomologous chromosomes No change in the total amount of genetic material �Reciprocal translocation� �Balanced translocation�

56. 56 CHROMOSOME STRUCTURE Balanced translocations Usually no phenotypic consequences Amount of genetic material is normal Rarely, phenotype can be altered due to position effects Inheritance can result in an unbalanced translocation Generally associated with phenotypic abnormalities Can be lethal

57. 57 CHROMOSOME STRUCTURE Unbalanced translocations Cause of familial Down syndrome Majority of chromosome 21 is attached to chromosome 14 Individual has three copies of most of the genes on chromosome 21 Characteristics similar to the more common form of Down syndrome Three copies of chromosome 21

58. 58 CHROMOSOME STRUCTURE Familial Down syndrome Example of a Robertsonian translocation Most common type of chromosome rearrangement in humans Centromeric regions of two nonhomologous acrocentric chromosomes become fused Breaks at extreme ends of short arms Small acentric fragments are lost Larger chromosomal segments fuse at centromeric regions Chromosome formed is metacentric or submetacentric

59. 59 CHROMOSOME STRUCTURE Individuals with balanced translocations Greater risk of producing gametes with unbalanced combinations of chromosomes Depends on meiosis I segregation pattern

60. 60 CHROMOSOME STRUCTURE Segregation of balanced translocations Homologous regions pair Translocation cross is formed

61. 61 CHROMOSOME STRUCTURE Segregation of balanced translocations Based on segregation of centromeres Three possible ways Alternate Adjacent-1 Adjacent-2 Rarest

62. 62 CHROMOSOME NUMBER Chromosome number can be altered in two ways Variation in the number of sets of chromosomes Euploid variation Variation in the number of a particular chromosome within a set Aneuploidy

63. 63 CHROMOSOME NUMBER Phenotypes of all species are influenced by thousands of genes ~35,000 genes in a single set of human chromosomes Most genes are expressed only in certain cell types or during certain times in development Intricate coordination is required in the expression of these genes Proper development often requires two copies of each gene per cell

64. 64 CHROMOSOME NUMBER Aneuploidy Alteration in the number of a particular chromosome within a set Commonly causes an abnormal phenotype Due to an alteration in the amount of gene product produced i.e., 150% if three copies, 50% if one copy, etc.

65. 65 CHROMOSOME NUMBER Aneuploidy Harmful effects first discovered in Jimson weed Datura stramonium Various trisomies had morphologically different capsules Many other morphologically distinguishable traits Many detrimental

66. 66 CHROMOSOME NUMBER Aneuploidy Causes abnormal phenotypes in humans Tolerated best with sex chromosomes Remember X inactivation?

67. 67 CHROMOSOME NUMBER Down syndrome Generally caused by trisomy 21 Affected by maternal age

68. 68 CHROMOSOME NUMBER Euploid organisms Chromosome number is an exact multiple of a chromosome set e.g., Haploid, diploid (2n), triploid (3n), etc. Polyploid = three or more sets Euploid variation can occur Occasionally in animals Quite frequently in plants

69. 69 CHROMOSOME NUMBER Variations in euploidy Occur naturally in a few animal species e.g., Honeybees Females are diploid Males (drones) are haploid (monoploid) Produced from unfertilized eggs

70. 70 CHROMOSOME NUMBER Variations in euploidy A few vertebrate polyploid animals have been discovered Certain amphibians and reptiles Separate diploid and polyploid species

71. 71 CHROMOSOME NUMBER Variations in euploidy can occur in certain tissues within an animal Diploid animals sometimes produce polyploid tissues e.g., Human liver cells can vary greatly in ploidy 3n, 4n, 8n, etc. �Endopolyploidy� Biological significance poorly understood Enhanced production of certain gene products?

72. 72 CHROMOSOME NUMBER Variations in euploidy can occur in certain tissues within an animal Diploid animals sometimes produce polyploid tissues e.g., Chromosomes in Drosophila salivary glands undergo repeated rounds of mitosis without cell division ~9 Doublings ? 500 copies of each chromosome Polytene chromosomes are produced Provides a unique opportunity to study chromosome structure and gene organization

73. 73 CHROMOSOME NUMBER Drosophila polytene chromosomes Drosophila possess 8 chromosomes per diploid cell Homologous chromosomes synapse and replicate Polytene structure is formed Centromeres of all four types of chromosomes are attached to the chromocenter

74. 74 CHROMOSOME NUMBER Drosophila polytene chromosomes Lend themselves to microscopic examination Can be seen during interphase 100-200 times larger than an average metaphase chromosome Normal chromosomes are not visible in interphase

75. 75 CHROMOSOME NUMBER Drosophila polytene chromosomes Exhibit a characteristic banding pattern Each dark band is a chromomere ~5,000 bands total More compact than interband regions Over 95% of DNA is in these bands

76. 76 CHROMOSOME NUMBER Drosophila polytene chromosomes Allow the study of the organization and functioning of interphase chromosomes in great detail Duplications, deletions, and other rearrangements readily detectable Expression patterns of particular genes can be correlated with changes in the compaction of certain bands

77. 77 CHROMOSOME NUMBER Variations in euploidy Common in plants 30 � 35% of ferns and angiosperms are polyploid Important in agriculture Many food plants are polyploid e.g., Fruits and grains Often display outstanding agricultural characteristics Often larger and more robust

78. 78 CHROMOSOME NUMBER Variations in euploidy Wheat (Triticum aestivum) is hexaploid Arose from the union of three closely related diploid species �Allohexaploid�

79. 79 CHROMOSOME NUMBER Variations in euploidy Polyploid ornamental plants often produce larger flowers than their diploid counterparts

80. 80 CHROMOSOME NUMBER Variations in euploidy Some polyploids have an even number of chromosome sets e.g., 4n, 6n, etc. Produce balanced gametes Equal segregation during meiosis I Fertile

81. 81 CHROMOSOME NUMBER Variations in euploidy Some polyploids have an odd number of chromosome sets e.g., 3n, 5n, etc. Produce highly aneuploid gametes Unequal segregation during meiosis I Generally sterile

82. 82 CHROMOSOME NUMBER Variations in euploidy Sterility is generally a detrimental trait Can be desirable agriculturally e.g., Seedless bananas and watermelons are triploid

83. 83 CHROMOSOME NUMBER Variations in euploidy Triploid domestic bananas are derived from ancestral diploid species Small black spots in the center are degenerate seeds Asexually propagated through cuttings

84. 84 CHROMOSOME NUMBER Variations in euploidy Triploid varieties of flowering plants have been developed Unweakened by seed bearing Increased blooms

85. 85 CHROMOSOME NUMBER Variations in chromosome number are fairly widespread Generally have a significant phenotypic impact Various causes Nondisjunction Improper segregation of chromosomes during anaphase Interspecies crosses

86. 86 CHROMOSOME NUMBER Nondisjunction May occur during meiosis �Meiotic nondisjunction May occur during mitosis �Mitotic nondisjunction�

87. 87 CHROMOSOME NUMBER Meiotic nondisjunction Can occur during meiosis I All resulting gametes are aberrant (aneuploid) Can occur during meiosis II Half of the resulting gametes are aberrant (aneuploid)

88. 88 CHROMOSOME NUMBER Meiotic nondisjunction Complete nondisjunction occurs in rare cases Diploid gamete is produced Chromosome number is not reduced Fertilization with a normal haploid gamete produce a triploid individual

89. 89 CHROMOSOME NUMBER Mitotic nondisjunction Improper segregation of chromosomes may happen after fertilization Part of the organism will contain cells genetically different from the rest of the organism �Mosaicism� Size and location or mosaic region depend on timing of nondisjunction

90. 90 CHROMOSOME NUMBER Mitotic nondisjunction Bilateral gynandromorph of Drosophila melanogaster Began as an XX individual X chromosome was lost in the first mitotic division Left half is XX and female Right half is XO and male

91. 91 CHROMOSOME NUMBER Changes in euploidy can occur by various different mechanisms Complete nondisjunction Results in autopolyploidy Increase in number of sets within a single species Result of interspecies crosses Generally between close evolutionary relatives More common Results in allopolyploidy Possess sets of chromosomes from different species

92. 92 CHROMOSOME NUMBER Autopolyploid individuals possess additional sets of chromosomes from the same species

93. 93 CHROMOSOME NUMBER Allopolyploidy can produce various combinations Individuals possessing one set of chromosomes from each of two species are termed allodiploid Allopolyploids contain a combination of autopolyploidy and allodiploidy

94. 94 CHROMOSOME NUMBER Individuals possessing one set of chromosomes from each of two species are termed allodiploid Hybrids between two species Such hybrids often possess desirable traits e.g., Traits of both parental species Often sterile Depends on the degree of similarity of the different species� chromosomes May be fertile if the two genomes are very similar

95. 95 CHROMOSOME NUMBER Individuals possessing one set of chromosomes from each of two species are termed allodiploid Roan antelope (Hippotragus equinus) and sable antelope (Hippotragus niger) have similar chromosomes Evolutionarily related chromosomes are homeologous Allodiploid hybrids are fertile

96. 96 CHROMOSOME NUMBER Georgi Karpchenko (1928) First to recognize the relationship between chromosome pairing and fertility Crossed a radish (Raphanus) and a cabbage (Brassica) Both are diploid with 18 chromosomes Allodiploids possessed 18 chromosomes Species are not closely related Chromosomes are distinctly different Cannot synapse in meiosis Hybrids are sterile

97. 97 CHROMOSOME NUMBER Georgi Karpchenko (1928) Crossed a radish (Raphanus) and a cabbage (Brassica) Most hybrids are sterile Rare offspring are produced Karyotyping revealed that they were allotetraploid Contain 36 chromosomes Allotetraploids are fertile

98. 98 CHROMOSOME NUMBER Georgi Karpchenko (1928) Allodiploids are sterile Allotetraploids are fertile

99. 99 CHROMOSOME NUMBER Georgi Karpchenko (1928) Crossed a radish (Raphanus) and a cabbage (Brassica) Some fertile allotetraploids are fertile Sadly, they were useless Possessed the leaves of a radish and the roots of a cabbage Demonstrated that it is possible to artificially produce a new self-perpetuating species

100. 100 CHROMOSOME NUMBER The development of polyploids is of interest among plant breeders Often exhibit desirable traits Various agents have been shown to promote nondisjunction Leads to polyploidy

101. 101 CHROMOSOME NUMBER The drug colchicine is commonly used to promote polyploidy Binds to tubulin in the spindle apparatus Interferes with normal chromosome segregation

102. 102 CHROMOSOME NUMBER Alfred Blakeslee and Amos Avery (1937) First to apply colchicine to plant tissue Able to cause complete nondisjunction Produced autotetraploids Can be propagated asexually from cuttings Tetraploid flowers are capable of sexual reproduction

103. 103 CHROMOSOME NUMBER Several mechanisms can produce variations in chromosome number Some of these processes can occur naturally Figure prominently in speciation and evolution

104. 104 CHROMOSOME NUMBER Individual cells can be mixed together and made to fuse �Cell fusion� Can create new strains of plants Enables crossing of species unable to interbreed naturally

105. 105 CHROMOSOME NUMBER The development of diploid crop strains homozygous for all of their genes is a goal of some plant breeders Two such true-breeding strains can be crossed to produce hybrids heterozygous for many genes Hybrid vigor (heterosis) can result

106. 106 CHROMOSOME NUMBER True-breeding strains can be produced after several rounds of self-fertilization Alternately, monoploids can be used to produce such strains Have been used to improve wheat, rice, corn, barley, and potato

107. 107 CHROMOSOME NUMBER Sipra Guha and Satish Maheshwari (1964) Developed a method to produce monoploid plants directly from pollen grains �Anther culture� Used extensively to produce entirely homozygous diploid strains