1. 1 Mitosis and Meiosis Traits are controlled by genes Each individual has thousands of genes and each gene has two copies in an individual. What are the physical entities that carry the genes during segregation and independent assortment? What is the biological basis for Mendel’s laws? greenxyellow yellow x yellow yellow: yellow:yellow:green

2. 2 Genes reside on Chromosomes Genes reside on chromosomes, Therefore understanding the behavior and inheritance patterns of individual genes requires an understanding of the behavior of inheritance patterns of chromosomes. The processes of mitosis and meiosis describe the two basic patterns of chromosome behavior in higher eukaryotes Mitosis: a form of cell division that produces two daughter cells of identical genotypes Meiosis: a form of cell division in a diploid cell that produces four haploid cells (not identical) Meiosis only occurs in a small specialized set of cells known as the germ cells.

3. 3 Development Mitosis2N ---->4N----> 2N+2N (somatic cells) Meiosis2N ---->4N---->N+N+N+N (germ cells) The segregation and assortment of chromosomes in germ cells is important in the transmission of traits 2N | 4N | N | 2N | 4N | 2N mitosis meiosis

4. 4 The Mitotic cell cycle The mitotic cycle alternates between the replication of each chromosome (S phase) and the segregation of the replicated chromosomes to two daughter nuclei (M phase). The intervals between these phases are known as gap phases and this divides the cell cycle into four phases M, G1, S and G2. Interphase consists of G1, S, and G2.

5. 5 Digression: Chromosome number Smallest number: The female of the ant, Myrmecia pilosula, has one pair of chromosomes per cell. Its male has only one chromosome in each cell. Largest number: The fern Ophioglossum reticulatum has about 630 pairs of chromosomes, or 1260 chromosomes per cell. SpeciesHaploid number (n) Human23 Monkey21 Mouse20 Frog13 Fruit fly4 C. Elegans6 Corn10 S. Cerevisiae16 S. Pombe3 n=2 Haploids are Diploids are Tetraploids are

6. 6 Mitosis Mitosis is the period in which the chromosomes condense align along the metaphase plate and migrate to opposite poles. In part because this is the most visibly dramatic stage in the cell cycle much research has focused on these mitotic events. Net result: The creation of two daughter cells with identical chromosome complements.

7. 7 Replication of DNA Each DNA mol is a chromatid The two chromatids attached to the centromere are called sister chromatids Homologous Chromosomes 99.99% identical Mitosis n=2 2N n=2 4N

8. 8 Mitosis Sister chromatids line up at the metaphase plate. Sister chromatids separate to opposite poles n=2 4N n=2 2N

9. 9 Mitosis in haploid and diploid Replication of DNA A a AA a a n=1 2N n=1 4N A a A a n=1 2N Replication of DNA A AA n=1 1N n=1 2N A A n=1 1N

10. 10 Cell cycle and cancer Currently the cell cycle/mitosis is an intensively investigated area of research. This is primarily due to the fact that: 1.The structural and regulatory components governing the cell cycle are conserved throughout the phyla. That is, the same proteins are used in yeast, flies and humans. 2. A number of the mutations that produce cancer in humans disrupt the genes involved in regulating cells during the cell cycle. Example: Cancers result from uncontrolled and inappropriate MITOTIC division of cells Cells actually contain a set of genes whose job it is to prevent cells from dividing inappropriately ( these genes are known as tumor suppressor genes, anti-oncogenes, and more poetically as the "guardians of the cell"). One gene known as p53 ensures that the chromosomes have replicated properly before allowing the cells to proceed into mitosis. Recently it has been found that lesions in this gene are one of the most common in all human cancers.

11. 11 Chromosomes Basic terms and key features of the chromosome: Telomere: end of chromosomes Centromere: It is the constricted region where the microtubules attach and help pull the sister chromatids apart during mitosis Sister chromatids: replicated chromatids in G2. The two sister chromatids are identical to one another. During prophase and metaphase they look like: Homologue- chromosome pair in a diploid. They are similar but not identical. Metaphase plate: the region midway between the two spindle poles in which the chromosomes align during metaphase Haploid (N)- the condition in which each chromosome is present in one copy (found in gametes) Diploid (2N): the condition in which each chromosome is present twice as members of a homologous pair A A AAaa

12. 12 Karyotype Description of length, number, morphology. Karyotype analysis is extremely important in medicine. Alternations in karyotypes are linked to birth defects and many human cancers. Metacentric- centromere in the middle Acrocentric- centromere towards the end Telocentric- centromere at the end

13. 13 Downs Downs Male Staining and specific banding pattern allows you to line up and identify various chromosomes Down's syndrome results from an individual possessing three copies of chromosome 21 rather than the normal two. It is the most common of all human defects and occurs in 1/200 conceptions and 1/900 births. Females over 35 years- segregation defect leading to three copies of chromosome 21 Karyotype analyses of fetus indicates whether the child has Downs. Trisomies occur with other chromosomes as well but usually lead to the death of the fetus XXY and XYY individuals are also found. Normal Male

14. 14 cri-du-chat The syndrome cri-du-chat is the result of a deletion in the short arm of human chromosome 5 The affected infant is mentally retarded and has abnormal development of the larynx. Consequently, the most characteristic symptom of the disorder is that their cry resembles that of a cat. sound recording of: Normal, Cat, cri-du-chat infant infant

15. 15 Meiosis Meiosis: While the mitotic cycle is designed to produce two cells with the identical genotype, the meiotic cycle is designed to produce four cells each with half of the chromosome complement. Meiosis allows the cell to maintain constant ploidy (following mating) and at the same time to shuffle the genetic deck (in the progeny) In meiosis: Diploid cells undergo one round of chromosome replication followed by two divisions thereby reducing ploidy and producing four haploid cells. The two divisions are referred to as Meiosis I and Meiosis II. N 2N-----> 4N----->N N

16. 16 Meiosis Meiosis I: Interphase I: chromosomes replicate Prophase I: chromosomes condense members of a chromosome pair (homologues) physically associate with one another and lie side by side on the metaphase plate. This process is known as synapsis. The paired chromosome physically overlap forming structures known as chiasma. Metaphase I: the paired homologous chromosomes, known as bivalents,move to the center of the cell and line up along the metaphase plate. Anaphase I: in a process known as disjunction, the members of a homologous pair migrate to opposite poles. This effectively reduces the total number of chromosomes by half and is therefore called a reductional division.

17. 17 Meiosis Telophase I: if this stage were equivalent to telophase of mitosis, the nuclear envelope would reform and DNA synthesis would take place. This does not occur and the anaphase meiotic products proceed directly into Prophase II of meiosis Net result: Four haploid meiotic products Meiosis II is analogous to mitosis; chromosomes, rather than homologous pairs align along the metaphase plate and the chromatids separate

18. 18

19. 19 MeiosisI Chromosomes replicate Homologous Chromosomes pair locate on metaphase plate at random This is Mendels random assortment OR

20. 20 Random assortment anaphaseI. Centromeres do not separate The two sister chromatids go to the same pole OR Reductional division

21. 21 MetaphaseIIa Cell division without intervening replication!! Similar to mitotic metaphase 25% The reduced number of chromosomes in each of the two cells align on the metaphase plate (no pairing of homologous occurs), divide to produce four haploid cells.

22. 22 MetaphaseIIb Cell division without intervening replication!! Similar to mitotic metaphase 25% The reduced number of chromosomes in each of the two cells align on the metaphase plate (no pairing of homologous occurs), divide to produce four haploid cells.

23. 23 Meiosis A a Bb AA a a bb BB AAa a bb BB AA BB a a bb A B A B a b a b AA bb a a BB A b A b a B a B

24. 24 With 23 human chromosomes, there is a possible 2 23 = 8.4 x 10 6 distinct gametes. Little Alberts 1 st edition 9-36 © Garland Publishing 1st mechanism for genetic diversity independent assortment of chromosomes Unlike mitosis, the meiotic products are not genetically identical The arrangement of paired homologous chromosomes on the plate in METAPHASE-I is RANDOM. Random arrangement leads to independent assortment of genes on different chromosomes

25. 25 Second mechanism of genetic diversity The paired homologues physically recombine (or crossover with one another).

26. 26 Crossing over There are two ways of generating variation: Random assortment of chromosomes (shuffling of maternal and paternal chromosomes). Recombination between homologous chromosomes (crossing-over) in metaphase I. Homologous chromosomes pair in metaphaseI At least one crossover occurs per homologous pair

27. 27 Crossing over is the result of a physical exchange between homologous chromosomes Cytological studies in maize by Creighton and McClintock (1931) were the first to demonstrate that recombination is the result of a physical exchange between homologous chromosomes On chromosome 9 in corn there were two markers: Endosperm composition: Seed color:

28. 28 The genetic recombinants were also cytological recombinants. This strongly supported the model that recombination involves a physical exchange between homologous chromosomes

29. 29 Mitosis and meiosis compared:

30. 30 Chromosome theory of inheritance As you all know genes reside on chromosomes. This basic fact is called the chromosome theory of inheritance. However earlier in this century, the issue of where the units of heredity resided was fiercely debated. The notion the genes were located on the chromosomes came from the recognition that the behavior of Mendel's particles during meiosis parallels the behavior of chromosomes at meiosis. 1 2 3 Mendel’s Laws of independent assortment imply that genes on the same chromosome are inherited together and genes on different chromosomes are inherited independently.

31. 31 chromosome theory of inheritance As you all know genes reside on chromosomes. This basic fact is called the chromosome theory of inheritance. However earlier in this century, the issue of where the units of heredity resided was fiercely debated. The notion that genes were located on chromosomes came from the recognition that the behavior of Mendel's particles during meiosis parallels the behavior of chromosomes during meiosis. 1. Genes are in pairs, so are chromosomes 2. Alleles of a gene segregate equally into gametes, so do the members of a homologous chromosome pair 3. Different genes act independently, so do different chromosomes Mendel’s Laws of independent assortment imply that genes on the same chromosome are inherited together and genes on different chromosomes are inherited independently.