1. The Chromosomal Basis of Inheritance15
The Chromosomal Basis of Inheritance
Lecture Presentation by Nicole Tunbridge and
Kathleen Fitzpatrick

2. Locating Genes Along Chromosomes
Mendel’s “hereditary factors” were purely abstract when first proposed
Today we can show that the factors—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

3. Figure 15.1
Figure 15.1 Where are Mendel’s hereditary factors located in the cell?

4. Figure 15.1a
Figure 15.1a Where are Mendel’s hereditary factors located in the cell? (part 1: mitosis, drawing)

5. Cytologists worked out the process of mitosis in 1875, using improved techniques of microscopy
Biologists began to see parallels between the behavior of Mendel’s proposed hereditary factors and chromosomes
Around 1902, Sutton and Boveri and others independently noted the parallels and the chromosome theory of inheritance began to form

6. Figure 15.2 The chromosomal basis of Mendel’s laws
P Generation
Yellow-round seeds (YYRR)
Green-wrinkled seeds (yyrr) Y r y Y R R r y
Meiosis
Fertilization
Gametes R Y y r
All F1 plants produce yellow-round seeds (YyRr).
F1 Generation R R y y r r Y Y
LAW OF SEGREGATION The two alleles for each gene separate.
Meiosis
LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently. R r r R
Metaphase I Y y Y y 1 1 R r r R
Anaphase I Y y Y y R r
Metaphase II r R
Figure 15.2 The chromosomal basis of Mendel’s laws 2 2 Y y Y y Y Y y y Y Y y y R R r r r r R R
1 4
1 4 yr
1 4
1 4 YR Yr yR
F2 Generation
An F1 × F1 cross-fertilization 3
Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 3
Fertilization recombines the R and r alleles at random. 9
: 3
: 3
: 1

7. Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr)
Figure 15.2a
P Generation
Yellow-round seeds (YYRR)
Green-wrinkled seeds (yyrr) Y y r R R r Y y
Meiosis
Fertilization R Y y r
Figure 15.2a The chromosomal basis of Mendel’s laws (part 1: P generation)
Gametes

8. All F1 plants produce yellow-round seeds (YyRr). F1 Generation
Figure 15.2b
All F1 plants produce yellow-round seeds (YyRr).
F1 Generation R R y y r r Y Y
LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently.
LAW OF SEGREGATION The two alleles for each gene separate.
Meiosis R r r R
Metaphase I Y y Y y 1 1 R r r R
Anaphase I Y y Y y
Metaphase II R r r R
Figure 15.2b The chromosomal basis of Mendel’s laws (part 2: F1 generation) 2 2 Y y Y y y Y Y y Y Y y y R R r r r r R R
1 4 YR
1 4
1 4 yr Yr
1 4 yR

9. LAW OF INDEPENDENT ASSORTMENT LAW OF SEGREGATION
Figure 15.2c
LAW OF INDEPENDENT ASSORTMENT
LAW OF SEGREGATION
F2 Generation 3
Fertilization recombines the R and r alleles at random.
An F1 × F1 cross-fertilization 3
Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 9
: 3
: 3
: 1
Figure 15.2c The chromosomal basis of Mendel’s laws (part 3: F2 generation)

10. Concept 15.1: Morgan showed that Mendelian inheritance has its physical basis in the behavior of chromosomes: Scientific inquiry
The first solid evidence associating a specific gene with a specific chromosome came in the early 20th century from the work of Thomas Hunt Morgan
These early experiments provided convincing evidence that the chromosomes are the location of Mendel’s heritable factors

11. Morgan’s Choice of Experimental Organism
For his work, Morgan chose to study Drosophila melanogaster, a common species of fruit fly
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

12. Morgan noted wild type, or normal, phenotypes that were common in the fly populations
Traits alternative to the wild type are called mutant phenotypes

13. Figure 15.3
Figure 15.3 Morgan’s first mutant

14. Figure 15.3a
Figure 15.3a Morgan’s first mutant (part 1: wild-type)

15. Figure 15.3b
Figure 15.3b Morgan’s first mutant (part 2: mutant)

16. 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 F1 generation all had red eyes
The F2 generation showed a 3:1 red to 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

17. Experiment Conclusion Results P Generation P Generation F1 Generation
Figure 15.4
Experiment
Conclusion
P Generation
P Generation w+ w X X X Y w+
F1 Generation
All offspring had red eyes. w
Sperm
Results
Eggs
F1 Generation w+ w+
F2 Generation w+ w w+
Sperm
Eggs
Figure 15.4 Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have? w+ w+
F2 Generation w+ w+ w w w w+

18. Experiment Results P Generation F1 Generation
Figure 15.4a
Experiment
P Generation
F1 Generation
All offspring had red eyes.
Results
Figure 15.4a Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have? (part 1: experiment and results)
F2 Generation

19. Conclusion P Generation Sperm Eggs F1 Generation Sperm Eggs
Figure 15.4b
Conclusion
P Generation w+ w X X X Y w+ w
Sperm
Eggs
F1 Generation w+ w+ w+ w w+
Sperm
Figure 15.4b Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have? (part 2: conclusion)
Eggs w+ w+
F2 Generation w+ w+ w w w w+

20. Concept 15.2: Sex-linked genes exhibit unique patterns of inheritance
Morgan’s discovery of a trait that correlated with the sex of flies was key to the development of the chromosome theory of inheritance
In humans and some other animals, there is a chromosomal basis of sex determination

21. 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
A person with two X chromosomes develops as a female, while a male develops from a zygote with one X and one Y
Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome

22. Figure 15.5 X Y
Figure 15.5 Human sex chromosomes

23. (d) The haplo-diploid system
Figure 15.6
44 + XY
Parents
44 + XX
or Sperm
22 + X
22 + X
22 + Y
Egg
76 + ZW
76 + ZZ
44 + XX
44 + XY or
Zygotes (offspring)
(a) The X-Y system
(c) The Z-W system
Figure 15.6 Some chromosomal systems of sex determination
32 (Diploid)
16 (Haploid)
22 + XX
22 + X
(b) The X-0 system
(d) The haplo-diploid system

24. Parents or Sperm Egg or Zygotes (offspring) (a) The X-Y system
Figure 15.6a
44 + XY
Parents
44 + XX
22 + X
22 + X
or Sperm
22 + Y
Egg
44 + XX
44 + XY or
Zygotes (offspring)
(a) The X-Y system
Figure 15.6a Some chromosomal systems of sex determination (part 1: X-Y and X-0 systems)
22 + XX
22 + X
(b) The X-0 system

25. (d) The haplo-diploid system
Figure 15.6b
76 + ZW
76 + ZZ
(c) The Z-W system
32 (Diploid)
16 (Haploid)
Figure 15.6b Some chromosomal systems of sex determination (part 2: Z-W and haplo-diploid systems)
(d) The haplo-diploid system

26. Short segments at the ends of the Y chromosomes are homologous with the X, allowing the two to behave like homologues during meiosis in males
A gene on the Y chromosome called SRY (sex-determining region on the Y) is responsible for development of the testes in an embryo

27. A gene that is located on either sex chromosome is called a sex-linked gene
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

28. SRY Gene
Testis-determining factor (TDF), also known as sex- determining region Y (SRY) protein, is a DNA-binding protein (also known as gene-regulatory protein/transcription factor) encoded by the SRY gene that is responsible for the initiation of male sex determination in humans. SRY is an intronless sex- determining gene on the Y chromosome in the placental mammals and marsupials, and mutations in this gene lead to a range of sex-related disorders with varying effects on an individual's phenotype and genotype

29. Crossing over during paternal meiosis prior to conception can cause SRY to be transferred from the Y chromosome to the X chromosome. The Y chromosome that results from this crossover is now lacking an SRY gene, and can no longer initiate testis development. When this chromosome is inherited from the father, the resulting offspring will have Swyer syndrome, characterized by a male karyotype (XY) and a female phenotype.

30. The X chromosome that results from this crossover event now has a SRY gene, and therefore the ability to initiate testis development. Offspring who inherit this chromosome will have a condition called XX male syndrome, characterized by an XX karyotype, and a male phenotype.

32. SRY has also been linked to the fact that males are more likely than females to develop dopamine-related diseases such as schizophrenia and Parkinson's disease. SRY encodes a protein that controls the concentration of dopamine, the neurotransmitter that carries signals from the brain that control movement and coordination.

33. Inheritance of X-Linked Genes
X chromosomes have genes for many characters unrelated to sex, whereas most Y-linked genes are related to sex determination

34. 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

35. Sperm Eggs Sperm Sperm Eggs Eggs (a) (b) (c) XNXN XnY Xn Y XN XNXn XNY
Figure 15.7
XNXN
XnY Xn Y
Sperm
Eggs XN
XNXn
XNY XN
XNXn
XNY
(a)
XNXn
XNY
XNXn
XnY
Figure 15.7 The transmission of X-linked recessive traits XN Y
Sperm Xn Y
Sperm
Eggs XN
XNXN
XNY
Eggs XN
XNXn
XNY Xn
XNXn
XnY Xn
XnXn
XnY
(b)
(c)

36. Some disorders caused by recessive alleles on the X chromosome in humans
Color blindness (mostly X-linked)
Duchenne muscular dystrophy
Hemophilia

37. 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

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

40. Figure 15.8a
Figure 15.8a X inactivation and the tortoiseshell cat (part 1: photo)

41. Concept 15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome
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

42. 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

43. Wild type (gray-normal)
Figure 15.9
Experiment
P Generation (homozygous)
Wild type (gray body, normal wings)
Double mutant (black body, vestigial wings)
b+ b+ vg+ vg+
b b vg vg
F1 dihybrid testcross
Homozygous recessive (black body, vestigial wings)
Wild-type F1 dihybrid (gray body, normal wings)
b+ b vg+ vg
b b vg vg
Testcross offspring
Eggs
b+ vg+
b vg
b+ vg
b vg+
Wild type (gray-normal)
Black- vestigial
Gray- vestigial
Black- normal
b vg
Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?
Sperm
b+ b vg+ vg
b b vg vg
b+ b vg vg
b b vg+ vg
PREDICTED RATIOS
Genes on different chromosomes:
: : :
Genes on the same chromosome:
: : :
Results
: : :

44. b+ b+ vg+ vg+ b b vg vg b+ b vg+ vg b b vg vg Experiment
Figure 15.9a
Experiment
P Generation (homozygous)
Wild type (gray body, normal wings)
Double mutant (black body, vestigial wings)
b+ b+ vg+ vg+
b b vg vg
F1 dihybrid testcross
Homozygous recessive (black body, vestigial wings)
Wild-type F1 dihybrid (gray body, normal wings)
Figure 15.9a Inquiry: How does linkage between two genes affect inheritance of characters? (part 1: experiment)
b+ b vg+ vg
b b vg vg

45. Wild type (gray-normal)
Figure 15.9b
Experiment
Testcross offspring
Eggs
b+ vg+
b vg
b+ vg
b vg+
Wild type (gray-normal)
Black- vestigial
Gray- vestigial
Black- normal
b vg
Sperm
b+ b vg+ vg
b b vg vg
b+ b vg vg
b b vg+ vg
PREDICTED RATIOS
Figure 15.9b Inquiry: How does linkage between two genes affect inheritance of characters? (part 2: results)
Genes on different chromosomes:
: : :
Genes on the same chromosome:
: : :
Results
: : :

46. 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

47. F1 dihybrid female and homozygous recessive male in testcross
Figure 15.UN01
b+ vg+
b vg
F1 dihybrid female and homozygous
recessive male in testcross
b vg
b vg
b+ vg+
b vg
Most offspring or
Figure 15.UN01 In-text figure, testcross, p. 300
b vg
b vg

48. 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

49. Genetic Recombination and Linkage
The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination

50. Recombination of Unlinked Genes: Independent Assortment of Chromosomes
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

51. Gametes from yellow-round dihybrid parent (YyRr)
Figure 15.UN02
Gametes from yellow-round dihybrid parent (YyRr) YR yr Yr yR
Gametes from testcross homozygous recessive parent (yyrr) yr
YyRr
yyrr
Yyrr
yyRr
Figure 15.UN02 In-text figure, Punnett square, p. 300
Parental- type offspring
Recombinant offspring

52. 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

53. Figure 15.10 Chromosomal basis for recombination of linked genes
P generation (homozygous)
Wild type (gray body, normal wings)
Double mutant (black body, vestigial wings)
b+ vg+
b vg
b+ vg+
b vg
F1 dihybrid testcross
Wild-type F1 dihybrid (gray body, normal wings)
Homozygous recessive (black body, vestigial wings)
b+ vg+
b vg
b vg
b vg
Replication of chromosomes
Replication of chromosomes
b+ vg+
b vg
b+ vg+
b vg
b vg
b vg
b vg
b vg
Meiosis I
b+ vg+
Meiosis I and II
b+ vg
b vg+
b vg
Meiosis II
Recombinant chromosomes
Figure Chromosomal basis for recombination of linked genes
Eggs
b+ vg+
b vg
b+ vg
b vg+
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+
b vg
b vg
b vg
b vg
Sperm
Parental-type offspring
Recombinant offspring
Recombination frequency
391 recombinants 2,300 total offspring =
× 100 = 17%

54. P generation (homozygous)
Figure 15.10a
P generation (homozygous)
Wild type (gray body, normal wings)
Double mutant (black body, vestigial wings)
b+ vg+
b vg
b+ vg+
b vg
Wild-type F1 dihybrid (gray body, normal wings)
Figure 15.10a Chromosomal basis for recombination of linked genes (part 1: F1 dihybrid)
b+ vg+
b vg

55. Wild-type F1 dihybrid (gray body, normal wings)
Figure 15.10b
F1 dihybrid testcross
b+ vg+
b vg
Wild-type F1 dihybrid (gray body, normal wings)
Homozygous recessive (black body, vestigial wings)
b vg
b vg
b+ vg+
b vg
b+ vg+
b vg
b vg
b vg
b vg
b vg
Meiosis I
b+ vg+
b+ vg
Meiosis I and II
b vg+
Figure 15.10b Chromosomal basis for recombination of linked genes (part 2: testcross)
Recombinant chromosomes
b vg
Meiosis II
b+vg+
b vg
b+ vg
b vg+
b vg
Eggs
Sperm

56. Recombinant chromosomes
Figure 15.10c
Meiosis II
Recombinant chromosomes
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+
b vg
b vg
b vg
b vg
Sperm
Figure 15.10b Chromosomal basis for recombination of linked genes (part 3: testcross offspring)
Parental-type offspring
Recombinant offspring
Recombination frequency
391 recombinants 2,300 total offspring =
× 100 = 17%

57. Animation: Crossing Over