1. Chapter 3 The Chromosomal Basis of Heredity

2. Chromosomes
The chromosome complement = the complete set of chromosomes of plants and animals
The nucleus of each somatic cell contains a fixed number of chromosomes typical of the particular species
The number of chromosomes vary tremendously among species and have little relationship to the complexity of the organism

3. Chromosomes
The chromosomes in the nuclei of somatic cells are usually present in pairs. For example, the 46 chromosomes of human being consist of 23 pairs
Cells with nuclei of this sort, containing two similar sets of chromosomes, are called diploid

4. Chromosomes
The germ cells, or gametes, are haploid and contain only one set of chromosomes, consisting of one member of each of the pairs
The haploid gametes unite in fertilization to produce the diploid state of somatic cell
The chromosomes are present in pairs because one chromosome of each pair derives from the maternal parent of the organism and the other from its paternal parent

5. Mitosis
Mitosis is a precise process of nuclear division that ensures that each of two daughter cells receives a diploid complement of chromosomes identical with the diploid complement of the parent cell
Mitosis is usually accompanied by cytokinesis, the process in which the cell itself divides to yield two daughter cells

6. Cell Cycle
In a cell that is not undergoing mitosis, the chromosomes are invisible with a light microscope. This stage of the cell cycle is called interphase
DNA in the chromosomes is replicated during a period of interphase called S = DNA synthesis
Before and after S, there are periods, called G1 and G2, respectively
These three interphase are followed by mitosis, M

7. Figure 03.02: The cell cycle of a typical mammalian cell growing in tissue culture.

8. Stages of Mitosis
Prophase is marked by the condensation of chromosomes. Each chromosome is already longitudinally double, consisting of two subunits called chromatids
Each pair of chromatids is the product of the duplication of one chromosome in the S period of interphase
The chromatids in a pair are held together at a specific region of the chromosome called the centromere.

9. Prophase of Haemanthus
© Andrew S. Bajer - Research Projects

10. Stages of Mitosis
At the beginning of metaphase, the mitotic spindle forms
The spindle is a bipolar structure arching between the centrosomes that consists of microtubules
The spindle fibers attach to each chromosome in the region of the centromere called the kinetochore
The chromosomes move toward the center of the cell until all the kinetochores lie on an imaginary plane equidistant from the spindle poles = the metaphase plate

11. Metaphase of Haemanthus
© Andrew S. Bajer - Research Projects

12. Stages of Mitosis
In anaphase, the centromeres divide longitudinally, and the two sister chromatids of each chromosome move toward opposite poles of the spindle
Once the centromeres divide, each sister chromatid is regarded as a separate chromosome in its own right.

13. Anaphase of Haemanthus
© Andrew S. Bajer - Research Projects

14. Stages of Mitosis
In telophase, a nuclear envelope forms around each compact group of chromosomes, nucleoli are formed, and the spindle disappears
The chromosomes undergo decondensation until they are no longer visible as discrete entities
The two daughter nuclei assume a typical interphase appearance
The cytoplasm of the cell divides in two

15. Telophase of Haemanthus
© Andrew S. Bajer - Research Projects

16. Figure 03.03: Chromosome behavior during mitosis in an organism with two pairs of chromosome.

17. Meiosis
Meiosis is a mode of cell division in which cells are created that contain only one member of each pair of chromosomes
Meiosis consists of two successive nuclear divisions
Meiosis results in four daughter cells, each genetically different and each containing one haploid set of chromosomes

18. Figure 03.04: Behavior of a single pair of homologous chromosomes in meiosis

19. Meiosis
Meiosis is a more complex and considerably longer process than mitosis and usually requires days or even weeks
In animals, meiosis takes place in specific cells called meiocytes: the oocytes form egg cells and the spermatocytes form sperm cells
In the females of animals and plants, only one of the four products develops into a functional cell (the other three disintegrate)

20. Figure 03.05: The life cycle of a typical animal.

21. Meiosis
In plants, the products of meiosis form spores, which undergo one or more mitotic divisions to produce a haploid gametophyte organism
The gametophyte produces gametes by mitotic division of a haploid nucleus
Fusion of haploid gametes creates a diploid zygote that develops into the sporophyte plant, which undergoes meiosis to produce spores and so restarts the cycle

22. Figure 03.06: The life cycle of corn, Zea mays.

23. Outline of Meiosis
Prior to the first nuclear division, the members of each pair of chromosomes become closely associated along their length
The chromosomes that pair with each other are said to be homologous chromosomes
Each member of a pair of homologs consists of a duplex of two sister chromatids joined at the centromere. The pairing of the homologous chromosomes, therefore, produces a four-stranded structure

24. Outline of Meiosis
At the time of pairing, the homologs can exchange genes that results in chromosomes that consist of segments from one homolog intermixed with segments from the other
In the first nuclear division, the homologous chromosomes are separated from each other, one member of each pair going to opposite poles of the spindle
Two nuclei are formed, each containing a haploid set of duplex chromosomes

25. Outline of Meiosis
The second nuclear division resembles a mitotic division, but there is no DNA replication
At metaphase, the chromosomes align on the metaphase plate, and at anaphase, the chromatids are separated into opposite daughter nuclei
The net effect of the two divisions is the creation of four haploid nuclei, each containing the equivalent of a single sister chromatid from each pair of homologous chromosomes

26. Meiosis I
The first meiotic division—reductional division, reduces the chromosome number by half
Prophase I is the longest stage and is commonly divided into five substages: leptotene, zygotene, pachytene, diplotene, and diakinesis
These are descriptive terms that indicate the appearance of the chromosomes at each substage

27. Meiosis: Prophase I
Leptotene – the chromosomes first become visible as long, thread-like structures
Zygotene – synapsis of homologous chromosomes = bivalent
Pachytene – crossing-over between homologs
Parts A, B, and C courtesy of Marta Walters and Santa Barbara Botanic Gardens, Santa Barbara, California. Part D courtesy of Herbert Stern. Used with permission.

28. Figure 03.09AB: Bivalent consisting of a pair of homologous chromosomes.

29. Meiosis: Prophase I
Diplotene – chromosome repulsion, however, they remain held together by cross-connections resulting from crossing-over. Each cross-connection, called a chiasma, is formed by a breakage and rejoining between nonsister chromatids
Diakinesis – maximum chromosome contraction

30. Meiosis: Metaphase I
Metaphase I – the bivalents positioned with the centromeres of the two homologs on opposite sides of the metaphase plate
As each bivalent moves onto the metaphase plate, its centromeres are oriented at random with respect to the poles of the spindle
Genes on different chromosomes undergo independent assortment because nonhomologous chromosomes align at random in metaphase I

31. Figure 03.11AB: Independent assortment of genes on nonhomologous chromosomes.

32. Meiosis: Anaphase I
Anaphase I – homologous chromosomes, each composed of two chromatids joined at an undivided centromere, separate from one another and move to opposite poles of the spindle
The physical separation of homologous
chromosomes in anaphase I is the physical basis of
Mendel’s principle of segregation

33. Meiosis: Telophase I
Telophase I – a haploid set of chromosomes consisting of one homolog from each bivalent is located near each pole of the spindle
The spindle breaks down, the chromosomes enter the second meiotic division after only a limited uncoiling
Chromosome replication never takes place
between the two divisions

34. Meiosis II
The second meiotic division (meiosis II) is called the equational division because the chromosome number remains the same in each cell before and after the second division
In some species, the chromosomes pass directly from telophase I to prophase II without loss of condensation
After a short prophase II and the formation of second-division spindles, the centromeres of the chromosomes in each nucleus become aligned on the central plane of the spindle at metaphase II

35. Meiosis II
In anaphase II, the centromeres divide and the chromatids of each chromosome move to opposite poles of the spindle
Once the centromere has split at anaphase II, each chromatid is considered a separate chromosome
Telophase II is a transition to the interphase condition of the chromosomes in the four haploid nuclei, accompanied by division of the cytoplasm.

36. Meiosis vs. Mitosis
Meiosis produces four haploid cells: each contains one copy of each pair of homologous chromosomes which are usually not genetically identical because of crossing-over associated with the formation of chiasmata during prophase of the first division
Mitosis produces two diploid cells that contain both members of each pair of homologous chromosomes which are genetically identical

37. Chromosome Structure
Eukaryotic chromosomes are highly coiled stable complexes of DNA and protein called chromatin
Each eukaryotic chromosome contains a single DNA molecule of enormous length
Some of the proteins present in chromatin determine chromosome structure and the changes in structure during the cell cycle
Other chromatin proteins appear to have important roles in regulating chromosome functions

38. Figure 03.13A: Separations of chromosomes of yeast
Part A © 1988 Bio-Rad Laboratories, Inc.; permission to reproduce and to publish this image has been granted by Bio-Rad Laboratories, Inc. solely for the purpose of this publication. Any additional use outside of this textbook would require written permissioin.

39. Chromatin Structure
The nucleosome is the basic structural unit of chromatin
Each nucleosome is composed of a core particle, ~55 base pairs of DNA called linker DNA that links adjacent core particles and one molecule of histone H1 that binds to the core particle and to the linker DNA
Histones are small proteins that are highly conserved among different organisms

40. Figure 03.15A: Organization of nucleosomes.
Chromatin Structure
Each core particle consists of an octamere of pairs each of histone H2A, H2B, H3, and H4; a segment of DNA containing about 145 base pairs
Figure 03.15A: Organization of nucleosomes.

41. Figure 03.15B: Organization of nucleosomes.

42. Chromatin Structure
In the nucleus of a nondividing cell, chromatin fibers form discrete chromosome territories
Chromosome territories are correlated with gene densities
Territories of chromosome domains that are relatively gene rich tend to be located toward the interior of the nucleus
Figure 03.18: Chromosome territories formed by 30-nm chromatin fibers within the nucleus of a nondividing cell.
Figure courtesy of Tobias A. Knoch, Erasmus MC, Rotterdam, and Kirchhoff-Institute for Physics, Ruperto-Carola University, Heidelberg

43. Nucleosomes coil to form higher order DNA structure called the 30-
nm chromatin fiber
Figure 03.19: Condensation of DNA and chromatin to form a metaphase chromosome.

44. Chromatin Structure
The spaces between the chromatin domains form a network of channels large enough to allow passage of the molecular machinery for replication, transcription, and RNA processing
Replication takes place in small discrete regions that exhibit a reproducible temporal and spatial pattern, and transcription takes place in a few hundred discrete locations
The metaphase chromosome is a hierarchy of coiled coils

45. Chromatin Structure
Compact and heavily stained regions of chromatin are known as heterochromatin, which mainly consists of highly repeated noncoding DNA sequences—satellite DNA
The rest of the chromatin, which becomes visible only after chromosome condensation in mitosis or meiosis, is called euchromatin
The number of genes located in heterochromatin is small relative to the number in euchromatin

46. Figure 03.21A: Metaphase chromosomes of the ground squirrel.
Figure 03.21B: An interpretive drawing of metaphase chromosomes of the ground squirrel.
Part A courtesy of T.C. Hsu, Ph.D., and used with permission of Sen Pathak, Ph.D., Anderson Cancer Center, University of Texas.

47. Chromosome Structure
The centromere is essential for chromosome segregation
The centromere is a specific region of the eukaryotic chromosome. It serves as a central component of the kinetochore the complex of DNA and proteins to which the spindle fibers attach and move the chromosomes in both mitosis and meiosis

48. Figure 03.22: A yeast centromere.
Adapted from K. S. Bloom, M. Fitzgerald-Hayes, and
J. Carbon, Cold Spring Harb. Symp. Quant. Biol.
47 (1982): 1175.

49. Chromosome Structure
The telomere is essential for the stability of the chromosome tips
Due to the nature of DNA replication, chromosomes require special mechanism to restore DNA in telomeres in each cycle of replication
The mechanism relies on an enzyme called telomerase

50. Figure 03.25: The function of telomerase.

51. Figure 03.26: Telomere formation in Tetrahymena.

52. Figure 03.27: Chromosomal sex determination

53. Chromosomes and Heredity
Chromosome Theory of Heredity: Genes are located in chromosomes
Early evidence that genes are located on chromosomes was found by Thomas Hunt Morgan in 1910
Morgan’s studied inheritance patterns in Drosophila melanogaster and found that in some cases reciprocal crosses yield different results

54. Morgan’s Fruit Fly Experiments
Morgan realized that it might happen if the alleles for some genes were present in the X chromosome
The X chromosome is transmitted in a different pattern by males and females, and the Y chromosome does not contain alleles homologous to genes on the X chromosome

55. Figure 03.29: A chromosomal interpretation of results obtained in F1 and F2 progenies in crosses of Drosophila.

56. Nondisjunction
Experimental proof of the chromosome theory of heredity came from nondisjunction
Nondisjunction = chromosomes fail to separate (disjoin) and move to opposite poles of the division spindle, results in loss or gain of a chromosome
Calvin Bridges demonstrated that exceptional behavior of chromosomes is precisely paralleled by exceptional inheritance of their genes

57. Figure 03.32: The results of meiotic nondisjunction of the X chromosomes in a female Drosophila.

58. X-Linked Inheritance
Special chromosomes determine sex in many organisms
X and Y chromosomes = sex chromosomes, which are non-identical but share some genes
In most organisms, the Y chromosome carries few genes other than those related to male determination
X-linked genes are inherited according to sex
Hemophilia is a classic example of human X-linked inheritance

59. Figure 03.30: Genetic transmission of hemophilia A

60. X-Linked Inheritance
In many organisms, the male is the heterogametic sex
Males produce two different types of gametes: one containing X and another Y chromosome
Females have two X chromosomes and produce only X-bearing gametes
In some organisms (birds, butterflies, and some reptiles), females are heterogametic

61. Figure 03.31: Sex determination in birds: matched and unmatched sex chromosomes

62. Data analysis
Genetic data analysis makes use of probability and statistics
Progeny of crosses are predicted by the binomial probability
If the probability of possibility A is p and the probability of the alternative possibility B is q, then the probability that, in n trials, A is realized s times and B is realized t times is n!
psqt
s!t!

63. Chi-Square Analysis
The test of goodness of fit = test analyzes whether observed data agree with theoretical expectation
A conventional measure of goodness of fit is a value called chi-square, c2
c2 = ∑(observed – expected)2 / expected
A value of c2 = 0 means that the observed numbers fit the expected numbers perfectly

64. Chi-Square Analysis
Probability P that a worse fit (or one equally bad) would be obtained by chance, assuming that the genetic hypothesis is true
The critical values of P are conventionally chosen as 0.05 (the 5 percent level) and 0.01 (the 1 percent level)
Statistically significant refers to the magnitude of the difference between the observed and the expected numbers

65. Chi-Square Analysis
To determine the P value corresponding to a calculated c2 we need the number of degrees of freedom of the particular chi-square test
The number of degrees of freedom equals the number of classes of data minus 1

66. Figure 03.34: Graphs for interpreting goodness of fit to genetic predictions using the chi-square test.