1. 1 Mitosis and Meiosis Traits (phenotypes) 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 growth of cells, during human development

2. 2 Genes reside on Chromosomes Because genes reside on chromosomes, 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. 2N 2N4N 2N Meiosis: a form of cell division in a diploid cell that produces four haploid cells N 2N4N N Meiosis only occurs in a small specialized set of cells known as the germ cells.

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 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.

6. 6 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 diploid cell. SpeciesChromosome number in haploid cells (n) Human23 Monkey21 Mouse20 Frog13 Fruit fly4 C. Elegans6 Corn10 S. Cerevisiae16 S. Pombe3

7. 7 Chromosome number – “n” Haploids have 1N DNA content Diploids have 2N DNA content Tetraploids have 4N DNA content Chromosome number = Autosome + sex chromosome A B n=2 Totally different A a B b n=2 99.99% similar Totally different Diploid Haploid 99.99% similar

8. 8 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.

9. 9 Each DNA mol is a chromatid Two chromatids attached at centromere are sister chromatids Sister chromatids are 100% identical to each other Mitotic cell cycle in diploids Replication of DNA A a Bb AA a a bbBBHomologous Chromosomes 99.99% identical n=2 2N n=2 4N Sister chromatids centromere telomere Homologous chromosomes Aa AAaa

10. 10 Mitosis A a Bb AA a a bbBB Sister chromatids separate to opposite poles n=2 4N n=2 4N A a Bb Chromosomes line up at the metaphase plate.

11. 11 Mitosis A a Bb n=2 2N Can Mitosis occur in haploid cells? A a Bb Two cells created that are identical to original cell

12. 12 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

13. 13 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 mitotic 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). One gene known as p53 ensures that the chromosomes have replicated properly before allowing the cells to proceed into mitosis. Mutations in this gene are one of the most common in all human cancers.

14. 14 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: A A AAaa 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

15. 15 Karyotype Description of length, number, morphology of Chromosomes Karyotype analysis is extremely important in medicine. Cheap and quick way to detect chromosome loss and large alterations in chromosomes 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

16. 16 Downs Syndrome 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 Normal female XXY and XYY individuals are also found.

17. 17 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

18. 18 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 AND non-identical genotype. 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

19. 19 Meiosis-I Meiosis is divided into two parts- Meiosis I and Meiosis II Interphase I: chromosomes replicate Prophase I: chromosomes condense members of a chromosome pair (homologues) physically associate with one another and lie side by side near 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.

20. 20 Meiosis-II Telophase I: if this stage were equivalent to telophase of mitosis, the nuclear envelope would reform and then cells would undergo new round of DNA synthesis. This does not occur The anaphaseI 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

21. 21

22. 22 MeiosisI in diploid A a Bb AA a a bbBB Chromosomes replicate Homologous Chromosomes pair on metaphase plate at random This is Mendels random assortment AA a a bbB B aa A A bbBB OR N=2 N=4 n=2

23. 23 Random assortment anaphaseI. Centromeres do not separate The two sister chromatids go to the same pole OR Cell divides Reductional division AAa a bbBB AAa a bbBB AAa a bbBB AA a a bbBB OR (a)(b)

24. 24 MetaphaseIIa Cell division without intervening replication!! Similar to mitotic metaphase A B A B a b a b 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. AA BB a a bb Gamete

25. 25 MetaphaseIIb 25 Cell division without intervening replication!! Similar to mitotic metaphase A B A B a b a b 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. AA BB a a bb Gamete

26. 26 Meiosis A a Bb AA a a bb BB AA a 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 a a bb BB AA AA a a bb BB

27. 27 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

28. How did we get genetic diversity? 28 A B a b A a Bb A B A B a b a b A b A b a B a B

29. 29 Gene Shuffling Unlike mitosis, the meiotic products are not genetically identical. There are two reasons for this 1.The arrangement of paired homologous on the plate at Metaphase I is random. This random arrangement is the mechanism behind Mendel's principle of independent assortment ALSO 2.The paired homologues physically recombine (or crossover with one another).

30. 30 Crossing over There are two ways of generating genetic variation: Random assortment of chromosomes (shuffling of chromosomes) Recombination between homologous (maternal and paternal ) chromosomes (crossing-over) in metaphase I n=2 organism 4N ADAD ADAD adad adad Homologous chromosomes pair in metaphaseI At least one crossover occurs per homologous pair adad adad ADAD ADAD AnaphaseI ADAD AdAd aDaD adadB BC C b b C C B BC C b b C C b b C C A-D B-C A-d B-C a-D b-C a-d b-C AnaphaseII BCBC BC

31. 31 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: Wx waxy C colored wx starchy c colorless In addition, the chromosomes were morphologically distinct. Some had a cytologically visible structure known as a knob at the telomere and others had an interchange such that it is longer X w c w c w c F1 W C W C W C

32. 32 w c W C w c F2 w c W C The genetic recombinants were also cytological recombinants. This strongly supported the model that recombination involves a physical exchange between homologous chromosomes Recombinant X w c w c W c w c w C w c w c F1 heterozygous plant crossed to homozygous plant

33. 33 Mitosis and meiosis compared:

34. 34 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.