1. Copyright © 2010 Pearson Education Inc.
Lecture 03 – Chromosomal Inheritance Based on Chapter 12 – Chromosomal Basis of Inheritance
Copyright © 2010 Pearson Education Inc.

2. 1. The Chromosomal Basis of Inheritance – Chromosomes and Cellular Reproduction.
1.1. Cytology and genetics together were used to determine the association of genes and chromosomes.
1.2. Eukaryotic chromosomes are transmitted during cell division by mitosis and during reproduction by meiosis.

3. 2a. Eukaryotic Chromosomes
2.1. Eukaryotes have multiple linear chromosomes in a number characteristic of the species. Most have two versions of each chromosome and so are diploid (2N).
Diploid cells are produced by haploid (N) gametes that fuse to form a zygote. The zygote then undergoes development, forming a new individual.
Examples of diploid organisms are humans (23 pairs) and Drosophila melanogaster (4 pairs). The yeast Saccharomyces cerevisiae is haploid (16 chromosomes).
2.2. Chromosome pairs in diploid organisms are homologous chromosomes. One member of each pair (homolog) is inherited from each parent. Chromosomes that have different genes and do not pair are nonhomologous chromosomes (Figure 12.1).
Humans – 23 pairs – 46 chromosomes
Drosophila – 4 pairs – 8 chromosomes
Yeast – 16 pairs 32 chromosomes in diploid cells

4. 2b. Eukaryotic Chromosomes
Sex Chromosomes:
One sex has matched pair – e.g. human female XX
Other has unmatched pair – e.g. human male XY
Non sex chromosomes are called autosomes
2.3. Animals and some plants have male and female cells with distinct chromosome sets, due to sex chromosomes. One sex has a matched pair (e.g., human females with XX) and the other has an unmatched pair (human male with XY). Autosomes are chromosomes other than sex chromosomes.

5. 2c. Eukaryotic Chromosomes
2.4. Chromosomes differ in size and morphology. Each has a constriction called a centromere that is used in segregation during mitosis and meiosis. The centromere location is useful for identifying chromosomes (Figure 12.2).
Metacentric means the centromere is approximately in the center of the chromosome, producing two equal arms.
Submetacentric means one arm is somewhat longer than the other.
Acrocentric chromosomes have one long arm, and a short stalk and often a bulb (satellite) as the other arm.
Telocentric chromosomes have only one arm, because the centromere is at the end.

6. 2d. Eukaryotic Chromosomes
2.5. A karyotype shows the complete set of chromosomes in a cell. Metaphase chromosomes are used because they are easiest to see under the microscope after staining. The karyotype is species-specific.
The karyotype for a normal human male has 22 pairs of autosomes and 1 each of X and Y (Figure 12.3).
Human chromosomes are numbered from largest (1) to smallest (although 21 is actually smaller than 22).
Human chromosomes with similar morphologies are grouped (A through G).
Staining produces bands on the chromosomes, allowing easier identification. G banding is an example.
Chromosomes are partially digested with proteolytic enzymes, or treated with mild heat, and then stained with Giemsa stain. The dark bands produced are G bands.
In humans, metaphase chromosomes show about 300 G-bands, while about 2,000 can be distinguished in prophase.
Drawings (ideograms) show the G-banding pattern of human chromosomes.
Standard nomenclature is used to reference specific regions of the chromosomes.
a. The two arms are separated by the centromere, with the smaller one designated p and the larger q.
b. Regions and subregions are numbered from the centromere outward (1 is closest).
c. An example is the BRCA1 (breast cancer susceptibility) gene at 17q21 (long arm of chromosome 17 in region 21).
d. If a gene spans subregions, both are given. For example, the human cystic fibrosis gene is at 7q31.2–q31.3, spanning both subregions 2 and 3 on the long arm of chromosome 7.
e. Chromosome painting is a new technique that uses in situ hybridization with fluorescently labeled DNA probes to identify specific regions of particular chromosomes.

7. 3a. The Cell Cycle & Mitosis
3.1. Both unicellular and multicellular eukaryotes show a cell cycle, with growth, mitosis, and cell division (Figure 12.4). The cycle of somatic cells consists of:
Mitosis
Interphase, composed of:
Gap 1 (G1), when the cell prepares for chromosome replication.
Synthesis (S), when DNA replicates and new chromosomes are formed.
Gap 2 (G2), when the cell prepares for mitosis and cell division.
Relative time in each phase varies among cell types, with duration of G1 generally the deciding factor. Some cells exit G1 and enter a nondividing state called G0.
Interphase chromosomes are elongated and hard to see with light microscopy. Sister chromatids are held together by replicated but unseparated centromeres. The chromatids become visible in prophase and metaphase of mitosis. When the centromeres separate, they become daughter chromosomes.

8. 3b. The Cell Cycle & Mitosis
3.2. Mitosis is a continuous process, but geneticists divide it into five cytologically distinguishable stages (Figures 12.5 and 12.6):
Prophase is characterized by chromosomes condensing to a form visible by light microscopy.
The mitotic spindle, composed of microtubules made of tubulins, begins to form.
The nucleoli in the nucleus cease to be discrete areas in most species.
In animal cells, the centrioles replicate and become the focus for the aster (radial array of microtubules). During prophase, asters move from near each other and the nuclear envelope to the poles of the cell, spanned by the mitotic spindle.
The nuclear envelope begins to break down at the end of prophase
Prometaphase begins when the nuclear envelope breaks down.
Kinetochores form on the centromeres and attach the chromosomes to spindle microtubules.
Metaphase begins when the nuclear envelope has completely disappeared.
The kinetochore microtubules orient the chromosomes with their centromeres in a plane between the spindle poles, the metaphase plate.
The chromosomes reach a highly condensed state (Figure 12.7).
Anaphase begins when the centromeres of the sister chromatids separate.
The chromatids separate (disjunction) and daughter chromosomes move toward opposite poles by kinetochore microtubules.
Shape of the chromosomes moving toward the poles is defined by their centromere locations.
Cytokinesis usually begins near the end of anaphase.
Telophase is the period when migration of daughter chromosomes is completed.
Chromosomes begin to uncoil and form interphase chromosomes.
Nuclear envelope forms around each chromosome group.
Spindle microtubules disappear.
Nucleoli reform.
Nuclear division is complete, and the cell has two nuclei.

9. 3c. The Cell Cycle & Mitosis
Cytokinesis is division of the cytoplasm, compartmentalizing the new nuclei into separate daughter cells (Figure 12.8).
In animal cells, cytokinesis begins with a constriction in the center of the cell, which develops until two new cells are produced.
Most plant cells form a cell plate (membrane and wall) between the two nuclei, resulting in two progeny cells.
3.3. Gene segregation in mitosis is highly ordered so that each new cell receives a complete set of chromosomes (pairs in a diploid cell, and one of each type in a haploid cell).

10. 4a. Meiosis Stages of Meiosis Meiosis I Prophase I
4.1. Meiosis is two successive divisions of a diploid nucleus after only one DNA replication cycle. The result is haploid gametes (animals) or meiospores (plants). The two rounds of division in meiosis are meiosis I and meiosis II, each with a series of stages (Figure 12.9). Cytokinesis usually accompanies meiosis, producing four haploid cells from a single diploid cell.
4.2. Meiosis I: The First Meiotic Division – Meiosis I is when the chromosome information is reduced from diploid to haploid. It has five stages:
Prophase I is very similar to prophase of mitosis, except that homologous chromosomes pair and undergo crossing-over. The following substages of prophase I can be documented in many organisms:
Leptonema is when chromosomes begin to coil, committing the cell to the meiotic process.
In zygonema, chromosomes continue to condense, and synapsis, a tight association between homologous chromosomes, occurs. Telomeres are important in synapsis.
Pachynema occurs when synapsis is reached. The four-chromatid synaptonemal tetrad facilitates crossing-over.

11. 4b. Meiosis
Crossing-over is reciprocal exchange of chromosome segments between homologous chromosomes. If the homologs are not identical, new gene combinations (recombinant chromosomes) can result, but usually no genetic material is added or lost.

12. 4c. Meiosis Stages of Meiosis Meiosis I Prophase I Prometaphase I
Anaphase I
Telophase I
Meiosis II
Prophase II
Prometaphase II
Metaphase II
Anaphase II
Telophase II
Diplonema is the period when chromosomes begin to move apart, and chiasmata (singular is chiasma) formed by crossing-over become visible (Figure 12.10).
Diakinesis involves chromosomes condensing even more, and at this stage they are most easily counted.
Sex chromosomes are not homologous, but in some mammals behave as if they were due to a pseudoautosomal region (PAR) shared between X and Y. The PAR region enables crossing-over.
Prometaphase I involves breakdown of the nucleoli and nuclear envelope and entry of the meitic spindle into the former nuclear area. Kinetochore microtubules attach to the chromosomes.
Metaphase I has kinetochore microtubules aligning tetrads on the metaphase plate. It is distinguishable from metaphase of mitosis because pairs of homologous chromosomes align together to form tetrads.
Anaphase I is when tetrads separate, with chromosomes of each homologous pair disjoining. Resulting dyads migrate toward opposite poles, where new nuclei will form. This migration assumes that:
Centromeres derived from each parent will migrate randomly toward each pole.
Each pole will receive a haploid complement of replicated centromeres with associated chromosomes.
Sister chromatids will remain attached to each other (the major difference from mitosis).
Telophase I has dyads completing migration to the poles, and usually a nuclear envelope forms around each haploid grouping. Cytokinesis follows in most species, forming two haploid cells.
4.3. Meiosis II: The Second Meiotic Division - Meiosis II is very similar to mitotic division.
Prophase II: chromosomes condense and spindle forms.
Prometaphase II: nuclear envelopes (if any) break down, spindle organizes with kinetochore microtubules from opposite poles attached to kinetochores of each chromosome.
Metaphase II: chromosomes line up on metaphase plate.
Anaphase II: centromeres separate, and sister chromatids are pulled to opposite poles.
Telophase II: nuclear envelope forms around each set of chromosomes.
Cytokinesis usually takes place, and chromosomes become elongated and invisible with light microscopy.
4.4. After both rounds of meiotic division, four haploid cells (gametes in animals) are usually produced. Each has one chromosome from each homologous pair, but these are not exact copies due to crossing-over.

13. 4d. Meiosis
4.5. Gene Segregation in Meiosis – Meiosis has three significant results:
Haploid cells are produced because two rounds of division follow only one round of chromosome replication. Fusion of haploid cells restores the diploid number, maintaining a constant chromosome number through generations in sexually reproducing organisms.
Alignment of paternally and maternally derived chromosomes is random in metaphase I, resulting in random combinations of chromosomes in each nucleus generated (Figure 12.11).
The number of possible chromosome arrangements at the meiosis I metaphase plate is 2n21 (n is the number of chromosome pairs).
The number of possible chromosome combinations in nuclei produced by meiosis is 2n.
Due to differences between paternally and maternally derived chromosomes, many possibilities exist. Nuclei produced by meiosis will be genetically distinct from parental cells and from one another.
Crossing-over between maternal and paternal chromatid pairs during meiosis I provides still more variation, making the number of possible progeny nuclei extremely large

14. 5. Chromosome Theory of Inheritance
5.1. By the beginning of the twentieth century, cytologists had observed that chromosome number is constant in all cells of a species but varies widely between species (see Table 12.1).
5.2. Sutton and Boveri (1902) independently realized the parallel between Mendelian inheritance and chromosome transmission and proposed the chromosome theory of inheritance, which states that Mendelian factors (genes) are located on chromosomes.

15. 6. Sex Chromosomes
6.1. Behavior of sex chromosomes offers support for the chromosomal theory. In many animals sex chromosome composition relates to sex, while autosomes are constant
6.2. Independent work of McClung, Stevens, and Wilson indicated that chromosomes are different in male and female insects.
Stevens named the extra chromosome found in females “X.”
In grasshoppers, all eggs have an X; and half of the sperm produced have an X, and the other half do not. After fertilization, an unpaired X produces a male, while paired X chromosomes produce a female.
6.3. Other insects have a partner for the X chromosome. Stevens named it “Y.” In mealworms, for example, XX individuals are female, and XY are male.
6.4. In both humans and fruit flies (Drosophila melanogaster) females have two X chromosomes, while males have X and Y (Figure 12.15).
Males produce two kinds of gametes with respect to sex chromosomes (X or Y) and are called the heterogametic sex.
Females produce gametes with only one kind of sex chromosome (X) and are called the homogametic sex.
In some species the situation is reversed, with heterogametic females and homogametic males.
6.5. Random fusion of gametes (Figure 12.16) produces an F1 that is 1⁄2 female (XX) and 1⁄2 male (XY).

16. 7. Sex Linkage
7.1. Morgan (1910) found a mutant white-eyed male fly and used it in a series of experiments that showed a gene for eye color located on the X chromosome.
First, he crossed the white-eyed male with a wild-type (red-eyed) female. All F1 flies had red eyes. Therefore, the white-eyed trait is recessive.
Next, F1 were interbred. They produced an F2 with:
i. 3,470 red-eyed flies.
ii. 782 white-eyed flies.
The recessive number is too small to fit Mendelian ratios (the explanation, discovered later, is that white-eyed flies have lower viability).
All of the F2 white-eyed flies were male.
Cross is diagrammed in Figure 12.17, and Drosophila symbolism is explained in Box 12.1.
Morgan’s hypothesis was that this eye color gene is located on the X chromosome. If so,
Males are hemizygous, because there is no homologous gene on the Y. The original mutant male’s genotype was w/Y (hemizygous with the recessive allele).
Females may be homozygous or heterozygous. The wild-type female in the original cross was w+/w+ (homozygous for red eyes).
The F1 flies were w+/w (females) and w+/Y (males) (females all heterozygous, males hemizygous dominant).
The F2 data complete a crisscross inheritance pattern, with transmission from the mutant fly through his daughter (who is heterozygous) to his grandson. The F2 were:
Morgan’s hypothesis was confirmed by an experiment reciprocal to the original cross. A white-eyed female (w/w) was crossed with a wild-type male (w+/Y). Results of the reciprocal cross:
i. All F1 females had red eyes (w+/w).
ii. All F1 males had white eyes (w/Y).
These F1 results are different from those in the original cross, where all the F1 had red eyes. When the F1 from the reciprocal cross interbred, the F2 were:
7.2. Morgan’s discovery of X-linked inheritance showed that when results of reciprocal crosses are different, and ratios differ between progeny of different sexes, the gene involved is likely to be X-linked (sex-linked).
7.3. This was strong evidence that genes are located on chromosomes. Morgan received the 1933 Nobel Prize for Physiology or Medicine for this work.