1. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Chapter 15 The Chromosomal Basis of Inheritance

2. What you need to know… How the chromosome theory of inheritance connects the physical movement of chromosomes in meiosis to Mendel’s laws of inheritance. The unique pattern of inheritance in sex-linked genes. How alteration of chromosomes number or structurally altered chromosomes (deletions, duplications, etc.) can cause genetic disorders. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

3. Overview: Locating Genes Along Chromosomes Mendel’s “hereditary factors” were genes, though this wasn’t known at the time 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

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 was said to account for Mendel’s laws of segregation and independent assortment Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

5. Fig. 15-2 P Generation Yellow-round seeds (YYRR) Y F 1 Generation Y R R R Y  r r r y y y Meiosis Fertilization Gametes Green-wrinkled seeds ( yyrr) All F 1 plants produce yellow-round seeds ( YyRr ) R R Y Y r r y y Meiosis R R Y Y r r y y Metaphase I Y Y RR r r y y Anaphase I r r y Y Metaphase II R Y R y y y y R R Y Y r r r r y Y Y R R yR Yr yr YR 1/41/4 1/41/4 1/41/4 1/41/4 F 2 Generation Gametes An F 1  F 1 cross-fertilization 9 : 3 : 1 LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation. LAW OF SEGREGATION The two alleles for each gene separate during gamete formation. 1 2 3 3 2 1

6. 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 Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

7. Morgan’s Choice of Experimental Organism Several characteristics make fruit flies a convenient organism for genetic studies: – They breed at a high rate – A generation can be bred every two weeks – They have only four pairs of chromosomes Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

8. Morgan noted wild type, or normal, phenotypes that were common in the fly populations Traits alternative to the wild type are called mutant phenotypes Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

9. Fig. 15-3

10. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

11. Fig. 15-4 P Generation F1F1 F2F2 All offspring had red eyes Sperm Eggs F1F1 F2F2 P Sperm Eggs   X X X Y CONCLUSION EXPERIMENT RESULTS w w w w w w w w + + + ++ w w ww w w w w w + + + + + +

12. 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 Sex-Linked Genes – one located on a sex chromosome (X or Y in humans) Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

13. 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 the X chromosome – The SRY gene on the Y chromosome codes for the development of testes Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

14. Fig. 15-5 X Y

15. 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 (X-O system, Z-W system, Haplo-diplo system) Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

16. Fig. 15-6 44 + XY Parents 44 + XX 22 + X 22 + X 22 + Y or + 44 + XX or Sperm Egg 44 + XY Zygotes (offspring) (a) The X-Y system 22 + XX 22 + X (b) The X-0 system 76 + ZW 76 + ZZ (c) The Z-W system 32 (Diploid) 16 (Haploid) (d) The haplo-diploid system

17. Inheritance of Sex-Linked Genes Sex chromosomes have genes for many characters unrelated to sex – A gene located on either sex chromosome is called a sex-linked gene – In humans, sex-linked usually refers to a gene on the larger X chromosome Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

18. Sex-linked genes follow specific patterns of inheritance For a recessive sex-linked trait to be expressed – A female needs two copies of the allele – A male needs only one copy of the allele Sex-linked recessive disorders are much more common in males than in females Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

19. Fig. 15-7 (a)(b) (c) XNXNXNXN XnYXnY XNXnXNXn   XNYXNY XNXnXNXn  XnYXnY Y XnXn Sperm Y XNXN Y XnXn XNXnXNXn Eggs XNXN XNXN XNXnXNXn XNYXNY XNYXNY XNXN XnXn XNXNXNXN XnXNXnXN XNYXNY XnYXnY XNXN XnXn XNXnXNXn XnXnXnXn XNYXNY XnYXnY

20. Some disorders caused by recessive alleles on the X chromosome in humans: – Color blindness – Duchenne muscular dystrophy – progressive weakening of muscles and loss of coordination; affected individuals rarely live past early 20s – Hemophilia – having blood with an inability to clot normally, caused by the absence of proteins required for blood clotting Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

21. X Inactivation in Female Mammals X- inactivation – regulates gene dosage in females; 1 of the 2 X chromosomes in each cell is randomly inactivated during embryonic development by methylation – 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

22. Fig. 15-8 X chromosomes Early embryo: Allele for orange fur Allele for black fur Cell division and X chromosome inactivation Two cell populations in adult cat: Active X Inactive X Black furOrange fur

23. Each chromosome has hundreds or thousands of genes Linked genes - Genes located on the same chromosome that tend to be inherited together Concept 15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

24. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

25. Fig. 15-UN1 b + vg + Parents in testcross Most offspring b + vg + b vg  or

26. Fig. 15-9-1 EXPERIMENT P Generation (homozygous) Wild type (gray body, normal wings ) Double mutant (black body, vestigial wings)  b b vg vg b + b + vg + vg +

27. Fig. 15-9-2 EXPERIMENT P Generation (homozygous) Wild type (gray body, normal wings ) Double mutant (black body, vestigial wings)  b b vg vg Double mutant TESTCROSS  b + b + vg + vg + F 1 dihybrid (wild type) b + b vg + vg

28. Fig. 15-9-3 EXPERIMENT P Generation (homozygous) Wild type (gray body, normal wings ) Double mutant (black body, vestigial wings)  b b vg vg Double mutant TESTCROSS  b + b + vg + vg + F 1 dihybrid (wild type) b + b vg + vg Testcross offspring Eggs b + vg + b vg b + vg b vg + Black- normal Gray- vestigial Black- vestigial Wild type (gray-normal) b vg Sperm b + b vg + vg b b vg vg b + b vg vg b b vg + vg

29. Fig. 15-9-4 EXPERIMENT P Generation (homozygous) RESULTS Wild type (gray body, normal wings ) Double mutant (black body, vestigial wings)  b b vg vg Double mutant TESTCROSS  b + b + vg + vg + F 1 dihybrid (wild type) b + b vg + vg Testcross offspring Eggs b + vg + b vg b + vg b vg + Black- normal Gray- vestigial Black- vestigial Wild type (gray-normal) b vg Sperm b + b vg + vg b b vg vg b + b vg vg b b vg + vg PREDICTED RATIOS If genes are located on different chromosomes: If genes are located on the same chromosome and parental alleles are always inherited together: 1 1 1 1 1 1 0 0 965 944206 185 : : : : : : : : :

30. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

31. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

32. Genetic Recombination and Linkage The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

33. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

34. Fig. 15-UN2 YyRr Gametes from green- wrinkled homozygous recessive parent ( yyrr ) Gametes from yellow-round heterozygous parent (YyRr) Parental- type offspring Recombinant offspring yr yyrrYyrr yyRr YRyr Yr yR

35. Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked, but the linkage was incomplete, as evident from recombinant phenotypes Morgan proposed that some process must sometimes break the physical connection between genes on the same chromosome That mechanism was the crossing over of homologous chromosomes Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Animation: Crossing Over Animation: Crossing Over

36. Fig. 15-10 Testcross parents Replication of chromo- somes Gray body, normal wings (F 1 dihybrid) Black body, vestigial wings (double mutant) Replication of chromo- somes b + vg + b vg b + vg + b + vg b vg + b vg Recombinant chromosomes Meiosis I and II Meiosis I Meiosis II b vg + b + vg b vg b + vg + Eggs Testcross offspring 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal b + vg + b vg b + vg b vg b vg + Sperm b vg Parental-type offspringRecombinant offspring Recombination frequency = 391 recombinants 2,300 total offspring  100 = 17%

37. 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 the recombination frequency Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

38. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

39. Fig. 15-11 RESULTS Recombination frequencies Chromosome 9%9.5% 17% bcnvg

40. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

41. Fig. 15-12 Mutant phenotypes Short aristae Black body Cinnabar eyes Vestigial wings Brown eyes Red eyes Normal wings Red eyes Gray body Long aristae (appendages on head) Wild-type phenotypes 048.557.567.0104.5

42. Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

43. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

44. Fig. 15-13-1 Meiosis I (a) Nondisjunction of homologous chromosomes in meiosis I (b) Nondisjunction of sister chromatids in meiosis II Nondisjunction

45. Fig. 15-13-2 Meiosis I Nondisjunction (a) Nondisjunction of homologous chromosomes in meiosis I (b) Nondisjunction of sister chromatids in meiosis II Meiosis II Nondisjunction

46. Fig. 15-13-3 Meiosis I Nondisjunction (a) Nondisjunction of homologous chromosomes in meiosis I (b) Nondisjunction of sister chromatids in meiosis II Meiosis II Nondisjunction Gametes Number of chromosomes n + 1 n – 1 nn

47. Aneuploidy results from the fertilization of gametes in which nondisjunction occurred Offspring with this condition have an abnormal number of a particular chromosome Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

48. A monosomic zygote has only one copy of a particular chromosome A trisomic zygote has three copies of a particular chromosome Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

49. Polyploidy 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

50. Fig. 15-14

51. Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure: – Deletion removes a chromosomal segment – Duplication repeats a segment – Inversion reverses a segment within a chromosome – Translocation moves a segment from one chromosome to another Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

52. Fig. 15-15 Deletion A B C D E F G HA B C E F G H (a) (b) (c) (d) Duplication Inversion Reciprocal translocation A B C D E F G H A B C B C D E F G H A D C B E F G H M N O C D E F G H M N O P Q RA B P Q R

53. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

54. 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 Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

55. Fig. 15-16

56. Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes produces a variety of aneuploid conditions Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals; have sex organs but are sterile Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

57. Disorders Caused by Structurally Altered Chromosomes The syndrome cri du chat (“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 Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

58. Fig. 15-17 Normal chromosome 9 Normal chromosome 22 Reciprocal translocation Translocated chromosome 9 Translocated chromosome 22 (Philadelphia chromosome)

59. You should now be able to: 1.Explain the chromosomal theory of inheritance and its discovery 2.Explain why sex-linked diseases are more common in human males than females 3.Distinguish between sex-linked genes and linked genes 4.Explain how meiosis accounts for recombinant phenotypes 5.Explain how linkage maps are constructed Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

60. 6.Explain how nondisjunction can lead to aneuploidy 7.Define trisomy, triploidy, and polyploidy 8.Distinguish among deletions, duplications, inversions, and translocations 9.Explain genomic imprinting 10.Explain why extranuclear genes are not inherited in a Mendelian fashion Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings