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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

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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

2N 4N

2N

Meiosis: a form of cell division in a diploid cell that produces four haploid cells

N

N

2N 4N

N

N

Meiosis only occurs in a small specialized set of cells known as the germ cells.

Development

Mitosis 2N ---->4N ----> 2N+2N (somatic cells)

Meiosis 2N ---->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

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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.

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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.

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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.

Species Chromosome numberin haploid cells (n)

Human 23Monkey 21Mouse 20Frog 13Fruit fly 4C. Elegans 6Corn 10S. Cerevisiae 16S. Pombe 3

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Chromosome number – “n”

Haploids have 1N DNA contentDiploids have 2N DNA contentTetraploids 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

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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.

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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

B b

A A aa

bbB B

Homologous Chromosomes

99.99% identical

n=22N

n=24N

Sister chromatids

centromere

telomere

Homologous chromosomes

A a

A A a a

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Mitosis

Aa

B

b

A A

aa

bb

B B

Sister chromatids separate to opposite poles

n=24N

n=24N

A

a

B

b

Chromosomes line up at the metaphase plate.

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Mitosis

A

a

B

b

n=22N

Can Mitosis occur in haploid cells?

A

a

B

b

Two cells created that are identical to original cell

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Mitosis in haploid and diploid

Replication of DNA

A a

A A

aa

n=12N

n=14N

A

a

A

a

n=12N

Replication of DNA

A

A A

n=11N

n=12N

A A

n=11N

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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.

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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

A A a a

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

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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

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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.

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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

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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.

N2N -----> 4N----->N

NN

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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. 

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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

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MeiosisI in diploid

A a

B b

A A

aa

bb

B B

Chromosomes replicate

Homologous Chromosomes pair on metaphase plate at randomThis is Mendels random assortment

A A aa

bbB B

a a AA

bbB B

OR

N=2

N=4

n=2

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Random assortment

anaphaseI. Centromeres do not separateThe two sister chromatids go to the same pole

OR

Cell dividesReductional division

A A aa

bbB B

A Aaa

bbB B

A A aa

bbB B

A Aaa

bbB B

OR

(a) (b)

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MetaphaseIIa

Cell division without intervening replication!!

Similar to mitotic metaphase

A

B

A

B

a

b

a

b

25% 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.

A A

B B

aa

bb

Gamete

25

MetaphaseIIb

25

Cell division without intervening replication!!

Similar to mitotic metaphase

A

B

A

B

a

b

a

b

25% 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.

A A

B B

aa

bb

Gamete

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Meiosis A a

B b

A A aa

bbB B

A A aa

bbB B

A A

B B

aa

bb

A

B

A

B

a

b

a

b

A A

b b

aa

BB

A

b

A

b

a

B

a

B

aa

bb B B

A A

A A aa

bb B B

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With 23 human

chromosomes, there

is a possible 223 = 8.4

x 106 distinct

gametes.

Little Alberts 1st edition 9-36© Garland Publishing

1st mechanism for genetic diversity:independent assortment of chromosomes

How did we get genetic diversity?

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AB abA a

B b

A

B

A

B

a

b

a

b

A

b

A

b

a

B

a

B

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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).

30Crossing 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 organism4N

A D

A Da d

a d

Homologous chromosomes pair in metaphaseIAt least one crossover occurs per homologous pair

a d

a d

A D

A D

AnaphaseI

A D

A d

a D

a d

B

B C

Cb

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

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Crossing over is the result of a physical exchange

between homologous chromosomesCytological 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 cw c

w cF1

W CW C

W C

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w cW C w c

F2

w cW C

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

Recombinant

Recombinant

X

w cw c

W cw c

w Cw c

w c

F1 heterozygous plant crossed to homozygous plant

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Mitosis and meiosis compared:

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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.