1. LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson © 2011 Pearson Education, Inc. Lectures by Erin Barley Kathleen Fitzpatrick The Chromosomal Basis of Inheritance 遺傳的染色體學說 Chapter 15

2. Overview: Locating Genes Along Chromosomes Mendel’s “hereditary factors” were genes Today we can show that genes are located on chromosomes The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene © 2011 Pearson Education, Inc.

3. Figure 15.1

4. Concept 15.1: Mendelian inheritance has its physical basis in the behavior of chromosomes Mitosis and meiosis were first described in the late 1800s The chromosome theory of inheritance states: –Mendelian genes have specific loci (positions) on chromosomes –Chromosomes undergo segregation and independent assortment The behavior of chromosomes during meiosis can account for Mendel’s laws of segregation and independent assortment © 2011 Pearson Education, Inc.

5. Figure 15.2 P Generation F 1 Generation Yellow-round seeds ( YYRR ) Green-wrinkled seeds ( yyrr )  Meiosis Fertilization Gametes Y Y R R Y R y y r y r All F 1 plants produce yellow-round seeds ( YyRr ). Meiosis Metaphase I Anaphase I Metaphase II R R R R R R R R R R R R rr r r rr r r r r r r YY Y Y Y Y Y Y Y Y Y Y y y y y y y y y y y y y Gametes LAW OF SEGREGATION The two alleles for each gene separate during gamete formation. LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation. 12 21 1/41/4 1/41/4 1/41/4 1/41/4 YR yr Yr yR F 2 Generation 3 3 Fertilization recombines the R and r alleles at random. Fertilization results in the 9:3:3:1 phenotypic ratio in the F 2 generation. An F 1  F 1 cross-fertilization 9 : 3 : 1 r

6. Figure 15.2a P Generation Yellow-round seeds ( YYRR ) Green-wrinkled seeds ( yyrr )  Meiosis Fertilization Gametes Y Y R R Y R y y r y r r

7. Figure 15.2b F 1 Generation All F 1 plants produce yellow-round seeds ( YyRr ). Meiosis Metaphase I Anaphase I Metaphase II R R R R R R R R R R R R r r r r r r r r r r r r YY Y Y Y Y Y Y Y Y Y Y yy y y y y y y y y y y Gametes LAW OF SEGREGATION The two alleles for each gene separate during gamete formation. LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation. 12 21 1/41/4 1/41/4 1/41/4 1/41/4 YR yr Yr yR

8. Figure 15.2c F 2 Generation 3 Fertilization recombines the R and r alleles at random. Fertilization results in the 9:3:3:1 phenotypic ratio in the F 2 generation. An F 1  F 1 cross-fertilization 9 : 3 : 1 LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT 3

9. Morgan’s Experimental Evidence: Scientific Inquiry The first solid evidence associating a specific gene with a specific chromosome came from Thomas Hunt Morgan, an embryologist 胚胎發育學者 Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors © 2011 Pearson Education, Inc.

10. Morgan’s Choice of Experimental Organism Several characteristics make fruit flies a convenient organism for genetic studies –They produce many offspring –A generation can be bred every two weeks –They have only four pairs of chromosomes © 2011 Pearson Education, Inc.

11. Morgan noted wild type 野生型, or normal, phenotypes that were common in the fly populations Traits alternative to the wild type are called mutant phenotypes 突變型 © 2011 Pearson Education, Inc.

12. Figure 15.3

13. Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) –The F 1 generation all had red eyes –The F 2 generation showed the 3:1 red:white eye ratio, but only males had white eyes Morgan determined that the white-eyed mutant allele must be located on the X chromosome Morgan’s finding supported the chromosome theory of inheritance © 2011 Pearson Education, Inc.

14. Figure 15.4 All offspring had red eyes. P Generation F 1 Generation F 2 Generation F 1 Generation P Generation Eggs Sperm X X X Y ww ww ww ww ww ww ww ww ww ww ww w w w w ww RESULTS EXPERIMENT CONCLUSION

15. Figure 15.4a All offspring had red eyes. P Generation F 1 Generation F 2 Generation RESULTS EXPERIMENT

16. Figure 15.4b F 2 Generation P Generation Eggs Sperm X ww CONCLUSION X X Y ww ww ww ww ww ww ww ww ww ww w w w w w w F 1 Generation

17. Concept 15.2: Sex-linked genes exhibit unique patterns of inheritance In humans and some other animals, there is a chromosomal basis of sex determination © 2011 Pearson Education, Inc.

18. The Chromosomal Basis of Sex In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosome Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome The SRY gene on the Y chromosome codes for a protein that directs the development of male anatomical features © 2011 Pearson Education, Inc.

19. Figure 15.5 X Y

20. Females are XX, and males are XY Each ovum contains an X chromosome, while a sperm may contain either an X or a Y chromosome Other animals have different methods of sex determination © 2011 Pearson Education, Inc.

21. Figure 15.6 Parents or Sperm or Egg Zygotes (offspring) 44  XY 44  XX 22  X 22  Y 22  X 44  XX 44  XY 22  XX 22  X 76  ZW 76  ZZ 32 (Diploid) 16 (Haploid) (a) The X-Y system (b) The X-0 system (c) The Z-W system (d) The haplo-diploid system

22. Figure 15.6a Parents or Sperm or Egg Zygotes (offspring) 44  XY 44  XX 22  X 22  Y 22  X 44  XX 44  XY 22  XX 22  X (a) The X-Y system (b) The X-0 system

23. Figure 15.6b 76  ZW 76  ZZ 32 (Diploid) 16 (Haploid) (c) The Z-W system (d) The haplo-diploid system

24. A gene that is located on either sex chromosome is called a sex-linked gene 性聯遺傳基因 Genes on the Y chromosome are called Y- linked genes; there are few of these Genes on the X chromosome are called X- linked genes © 2011 Pearson Education, Inc.

25. Inheritance of X-Linked Genes X chromosome have genes for many characters unrelated to sex, whereas the Y chromosome mainly encodes genes related to sex determination © 2011 Pearson Education, Inc.

26. X-linked genes follow specific patterns of inheritance For a recessive X-linked trait to be expressed –A female needs two copies of the allele (homozygous) –A male needs only one copy of the allele (hemizygous) X-linked recessive disorders are much more common in males than in females © 2011 Pearson Education, Inc.

27. Figure 15.7 Eggs Sperm (a) (b) (c) XNXNXNXN XnYXnY XNXnXNXn XNYXNY XNXnXNXn XnYXnY XnXn Y XNXN Y Y XnXn XnXn XnXn XNXN XNXN XNXN XNXN XNXnXNXn XNYXNY XNYXNY XNYXNYXNYXNY XnYXnY XnYXnY XNXnXNXn XNXnXNXn XNXnXNXn XNXNXNXN XnXnXnXn

28. Some disorders caused by recessive alleles on the X chromosome in humans –Color blindness (mostly X-linked) 色盲 –Duchenne muscular dystrophy 裘馨氏肌肉萎 縮症 蛋白質失養素 (Dystrophin) –Hemophilia 血友病 © 2011 Pearson Education, Inc.

29. X Inactivation in Female Mammals In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development The inactive X condenses into a Barr body If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character © 2011 Pearson Education, Inc.

30. Figure 15.8 Early embryo: X chromosomes Allele for orange fur Allele for black fur Two cell populations in adult cat: Cell division and X chromosome inactivation Active X Inactive X Active X Black fur Orange fur

31. Each chromosome has hundreds or thousands of genes (except the Y chromosome) Genes located on the same chromosome that tend to be inherited together are called linked genes Concept 15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome © 2011 Pearson Education, Inc.

32. How Linkage Affects Inheritance Morgan did other experiments with fruit flies to see how linkage affects inheritance of two characters Morgan crossed flies that differed in traits of body color and wing size © 2011 Pearson Education, Inc.

33. Figure 15.9-1 P Generation (homozygous) Wild type (gray body, normal wings) b  b  vg  vg  b b vg vg Double mutant (black body, vestigial wings) EXPERIMENT

34. Figure 15.9-2 P Generation (homozygous) Wild type (gray body, normal wings) F 1 dihybrid (wild type) TESTCROSS b  b  vg  vg  b  b vg  vg b b vg vg Double mutant (black body, vestigial wings) Double mutant EXPERIMENT

35. Figure 15.9-3 P Generation (homozygous) Wild type (gray body, normal wings) F 1 dihybrid (wild type) Testcross offspring TESTCROSS b  b  vg  vg  b  b vg  vg b b vg vg Double mutant (black body, vestigial wings) Double mutant Eggs Sperm EXPERIMENT Wild type (gray-normal) Black- vestigial Gray- vestigial Black- normal b  vg  b vg b  vgb vg  b  b vg  vg b b vg vgb  b vg vgb b vg  vg b vg

36. Figure 15.9-4 P Generation (homozygous) Wild type (gray body, normal wings) F 1 dihybrid (wild type) Testcross offspring TESTCROSS b  b  vg  vg  b  b vg  vg b b vg vg Double mutant (black body, vestigial wings) Double mutant Eggs Sperm EXPERIMENT RESULTS PREDICTED RATIOS Wild type (gray-normal) Black- vestigial Gray- vestigial Black- normal b  vg  b vg b  vgb vg  b  b vg  vg b b vg vgb  b vg vgb b vg  vg 965 944 206 185 1 1 1 1 1 0 1 0 If genes are located on different chromosomes: If genes are located on the same chromosome and parental alleles are always inherited together: : : : : : : : : : b vg

37. Morgan found that body color and wing size are usually inherited together in specific combinations (parental phenotypes) He noted that these genes do not assort independently, and reasoned that they were on the same chromosome © 2011 Pearson Education, Inc.

38. Figure 15.UN01 Most offspring F 1 dihybrid female and homozygous recessive male in testcross or b + vg + b vg b + vg + b vg

39. However, nonparental phenotypes were also produced Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent © 2011 Pearson Education, Inc.

40. Genetic Recombination and Linkage The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination © 2011 Pearson Education, Inc.

41. Recombination of Unlinked Genes: Independent Assortment of Chromosomes Mendel observed that combinations of traits in some offspring differ from either parent Offspring with a phenotype matching one of the parental phenotypes are called parental types Offspring with nonparental phenotypes (new combinations of traits) are called recombinant types, or recombinants A 50% frequency of recombination is observed for any two genes on different chromosomes © 2011 Pearson Education, Inc.

42. Figure 15.UN02 Gametes from green- wrinkled homozygous recessive parent ( yyrr ) Gametes from yellow-round dihybrid parent ( YyRr ) Recombinant offspring Parental- type offspring YR yr Yr yR yr YyRr yyrr Yyrr yyRr

43. Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed He proposed that some process must occasionally break the physical connection between genes on the same chromosome That mechanism was the crossing over of homologous chromosomes © 2011 Pearson Education, Inc.

44. Animation: Crossing Over Right-click slide / select”Play”

45. Figure 15.10 Testcross parents Replication of chromosomes Gray body, normal wings (F 1 dihybrid) Black body, vestigial wings (double mutant) Replication of chromosomes Meiosis I Meiosis II Meiosis I and II Recombinant chromosomes Eggs b  vg  b vg b  vg  b  vg b vg  b vg b  vg  b  vg b vg b vg  Testcross offspring 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Sperm Parental-type offspring Recombinant offspring Recombination frequency 391 recombinants 2,300 total offspring  100  17%  b  vg  b vg  b  vg b vg

46. Figure 15.10a Testcross parents Replication of chromosomes Gray body, normal wings (F 1 dihybrid) Black body, vestigial wings (double mutant) Replication of chromosomes Meiosis I Meiosis II Meiosis I and II Recombinant chromosomes Eggs b  vg  b vg b  vg  b  vg b vg  b vg b  vg  b  vg b vg b vg  Sperm b vg

47. Figure 15.10b Testcross offspring 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Sperm Parental-type offspringRecombinant offspring Recombination frequency 391 recombinants 2,300 total offspring  100  17%  b  vg  b vg  b  vg b vg Eggs Recombinant chromosomes b  vg  b vg b  vg b vg 

48. New Combinations of Alleles: Variation for Normal Selection Recombinant chromosomes bring alleles together in new combinations in gametes Random fertilization increases even further the number of variant combinations that can be produced This abundance of genetic variation is the raw material upon which natural selection works © 2011 Pearson Education, Inc.

49. Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher therecombination frequency 兩基因距離越遠重組率越高 © 2011 Pearson Education, Inc.

50. A linkage map is a genetic map of a chromosome based on recombination frequencies Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency Map units indicate relative distance and order, not precise locations of genes © 2011 Pearson Education, Inc.

51. Figure 15.11 Chromosome Recombination frequencies 9% 9.5% 17% b cn vg RESULTS

52. Genes that are far apart on the same chromosome can have a recombination frequency near 50% Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes © 2011 Pearson Education, Inc.

53. Sturtevant used recombination frequencies to make linkage maps of fruit fly genes Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes Cytogenetic maps indicate the positions of genes with respect to chromosomal features © 2011 Pearson Education, Inc.

54. Figure 15.12 Mutant phenotypes Short aristae Black body Cinnabar eyes Vestigial wings Brown eyes Long aristae (appendages on head) Gray body Red eyes Normal wings Red eyes Wild-type phenotypes 104.5 67.057.5 48.5 0

55. Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders Plants tolerate such genetic changes better than animals do © 2011 Pearson Education, Inc.

56. Abnormal Chromosome Number In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy 不分離 ( 細胞分裂時成對的染色體無法分開 ) © 2011 Pearson Education, Inc.

57. Meiosis I Nondisjunction Figure 15.13-1

58. Meiosis I Meiosis II Nondisjunction Non- disjunction Figure 15.13-2

59. Meiosis I Meiosis II Nondisjunction Non- disjunction Gametes Number of chromosomes Nondisjunction of homo- logous chromosomes in meiosis I (a) Nondisjunction of sister chromatids in meiosis II (b) n  1 n  1 n  1 n  1 n  1 n n Figure 15.13-3

60. Aneuploidy 非整倍性 results from the fertilization of gametes in which nondisjunction occurred Offspring with this condition have an abnormal number of a particular chromosome © 2011 Pearson Education, Inc.

61. A monosomic zygote has only one copy of a particular chromosome A trisomic zygote has three copies of a particular chromosome © 2011 Pearson Education, Inc.

62. Polyploidy 多倍體 is a condition in which an organism has more than two complete sets of chromosomes –Triploidy (3n) is three sets of chromosomes –Tetraploidy (4n) is four sets of chromosomes Polyploidy is common in plants, but not animals Polyploids are more normal in appearance than aneuploids © 2011 Pearson Education, Inc.

63. Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure –Deletion 刪除 removes a chromosomal segment –Duplication 重製 repeats a segment –Inversion 倒置 reverses orientation of a segment within a chromosome –Translocation 轉位 moves a segment from one chromosome to another © 2011 Pearson Education, Inc.

64. Figure 15.14 (a) Deletion (b) Duplication (c) Inversion (d) Translocation A deletion removes a chromosomal segment. A duplication repeats a segment. An inversion reverses a segment within a chromosome. A translocation moves a segment from one chromosome to a nonhomologous chromosome. ABCDEFGH ABCEFGH ABCDEFGH ABCDEFGHBC ABCDEFGH ADCBEFGH ABCDEFGH MNOPQR G MNOC HFED ABPQ R

65. Figure 15.14a (a) Deletion (b) Duplication A deletion removes a chromosomal segment. A duplication repeats a segment. BACDEFGH ABCDEFGH ABCDEFGHBC ABCEFGH

66. Figure 15.14b (c) Inversion (d) Translocation An inversion reverses a segment within a chromosome. A translocation moves a segment from one chromosome to a nonhomologous chromosome. ABCDEFGH ADCBEFGH ABC D EFGH MNOPQR G MNOC HFED ABPQ R

67. Human Disorders Due to Chromosomal Alterations Alterations of chromosome number and structure are associated with some serious disorders Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy © 2011 Pearson Education, Inc.

68. Down Syndrome (Trisomy 21) Down syndrome is an aneuploid condition that results from three copies of chromosome 21 It affects about one out of every 700 children born in the United States The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained © 2011 Pearson Education, Inc.

69. Figure 15.15

70. Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes produces a variety of aneuploid conditions Klinefelter syndrome 柯林菲特氏症 is the result of an extra chromosome in a male, producing XXY individuals 臨床症狀為高瘦的身材，青春期後出現男性女 乳現象，鬍鬚及體毛較少，生殖器在成年之前 與常人相同，之後則發育不良，睾丸較小且陰 莖較短，恥毛分布如女性，絕大多數患者均不 育。其智商正常，平均約 90 ，半數的病人早年 會有語言發展遲緩現象。 © 2011 Pearson Education, Inc.

71. Aneuploidy of Sex Chromosomes Monosomy X, called Turner syndrome 透 納氏症, produces X0 females, who are sterile; it is the only known viable monosomy in humans 身材矮小、幼稚型性徵（第二性徵不明 顯）、蹼狀頸與肘外翻的婦女稱之為透納 氏症。百分之 99% 的（ 45, X ）胚胎會流 產，但若活產就會變成透納氏症。 © 2011 Pearson Education, Inc.

72. Disorders Caused by Structurally Altered Chromosomes The syndrome cri du chat 貓鳴症候群 (“cry of the cat”), results from a specific deletion in chromosome 5 A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood © 2011 Pearson Education, Inc.

73. Disorders Caused by Structurally Altered Chromosomes Certain cancers, including chronic myelogenous leukemia (CML) 慢性骨髓 性白血病, are caused by translocations of chromosomes 造血母細胞的一種惡性腫瘤第 9 對染色 體上的一段 ABL 基因與第 22 對染色體上 的一段基因互換位子 ，而使得在第 22 對 染色體上產生一個異常的融合基因 (BCR-ABL) 。 © 2011 Pearson Education, Inc.

74. Figure 15.16 Normal chromosome 9 Normal chromosome 22 Reciprocal translocation Translocated chromosome 9 Translocated chromosome 22 (Philadelphia chromosome)

75. Concept 15.5: Some inheritance patterns are exceptions to standard Mendelian inheritance There are two normal exceptions to Mendelian genetics 非孟德爾遺傳 One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleus In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance © 2011 Pearson Education, Inc.

76. Genomic Imprinting 基因印痕 For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits Such variation in phenotype is called genomic imprinting Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production 基因表現隨親代的來源不同而有不同的遺 傳現象，通常為特定基因片段的甲基化 © 2011 Pearson Education, Inc.

77. Figure 15.17 (a) Homozygote Paternal chromosome Maternal chromosome Normal Igf2 allele is expressed. Normal Igf2 allele is not expressed. Normal-sized mouse (wild type) Mutant Igf2 allele inherited from mother Mutant Igf2 allele inherited from father Normal-sized mouse (wild type) Dwarf mouse (mutant) Normal Igf2 allele is expressed. Mutant Igf2 allele is expressed. Mutant Igf2 allele is not expressed. Normal Igf2 allele is not expressed. (b) Heterozygotes

78. Figure 15.17a (a) Homozygote Paternal chromosome Maternal chromosome Normal Igf2 allele is expressed. Normal Igf2 allele is not expressed. Normal-sized mouse (wild type)

79. Figure 15.17b Mutant Igf2 allele inherited from mother Mutant Igf2 allele inherited from father Normal-sized mouse (wild type) Dwarf mouse (mutant) Normal Igf2 allele is expressed. Mutant Igf2 allele is expressed. Mutant Igf2 allele is not expressed. Normal Igf2 allele is not expressed. (b) Heterozygotes

80. It appears that imprinting is the result of the methylation (addition of –CH 3 ) of cysteine nucleotides Genomic imprinting is thought to affect only a small fraction of mammalian genes Most imprinted genes are critical for embryonic development © 2011 Pearson Education, Inc.

81. Inheritance of Organelle Genes Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasm Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant © 2011 Pearson Education, Inc.

82. Figure 15.18

83. Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems –mitochondrial myopathy 線粒體肌病 –Leber’s hereditary optic neuropathy 賴博氏遺 傳性視覺神經症。 LHON 為粒腺體 DNA 在 MTND4 基因上產生變化，然表現型差異度大， 同時較好發於男性身上。 © 2011 Pearson Education, Inc.

84. Figure 15.UN03 P generation gametes Sperm Egg This F 1 cell has 2 n  6 chromo- somes and is heterozygous for all six genes shown ( AaBbCcDdEeFf ). Red  maternal; blue  paternal. Each chromosome has hundreds or thousands of genes. Four ( A, B, C, F ) are shown on this one. The alleles of unlinked genes are either on separate chromosomes (such as d and e ) or so far apart on the same chromosome ( c and f ) that they assort independently. Genes on the same chromo- some whose alleles are so close together that they do not assort independently (such as a, b, and c ) are said to be genetically linked. D C B A F E d c b a f e D C B A F e d E f c b a

85. Figure 15.UN04