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c h a p t e r

Mitosis, Meiosis, and
Gametogenesis

I. MITOSIS

(Figure 9-1)

■

Mitosis is the process by which a cell with the diploid number of chromosomes, which in
humans is 46, passes on the diploid number of chromosomes to daughter cells.

■

The term

diploid

is classically used to refer to a cell containing 46 chromosomes.

■

The term “

haploid

”

is classically used to refer to a cell containing 23 chromosomes.

■

Mitosis ensures that the diploid number of 46 chromosomes is maintained in cells.

■

Mitosis occurs at the end of a cell cycle. Phases of the cell cycle are:

A. G

(Gap) Phase.

The G

phase is the resting phase of the cell. The amount of time a cell spends

in G

is variable and depends on how actively a cell is dividing.

B. G

Phase.

The G

phase is the gap of time between mitosis (M phase) and DNA synthesis (S

phase). The G

phase is the phase where

RNA, protein, and organelle synthesis

occurs. The G

phase lasts about

5 hours

in a typical mammalian cell with a 16-hour cell cycle.

C. G

Checkpoint. Cdk2-cyclin D and Cdk2-cyclin E

mediate the

S phase

transition at the

checkpoint.

D. S (Synthesis) Phase.

The S phase is the phase where

DNA synthesis

occurs. The S phase lasts

about

7 hours

in a typical mammalian cell with a 16-hour cell cycle.

E. G

Phase.

The G

phase is the gap of time between DNA synthesis (S phase) and mitosis (M

phase). The G

phase is the phase where high levels of

ATP synthesis

occur. The G

phase lasts

about

3 hours

in a typical mammalian cell with a 16-hour cell cycle.

F. G

Checkpoint. Cdk1-cyclin A and Cdk1-cyclin B

mediate the

M phase

transition at the

checkpoint.

G. M (Mitosis) Phase.

The M phase is the phase where

cell division

occurs. The M phase is

divided into six stages called

prophase, prometaphase, metaphase, anaphase, telophase,

and

cytokinesis.

The M phase lasts about 1 hour in a typical mammalian cell with a 16-hour cell

cycle.

1. Prophase.

The chromatin condenses to form well-defined chromosomes. Each chromo-

some has been duplicated during the S phase and has a specific DNA sequence called the

centromere

that is required for proper segregation. The

centrosome complex,

which is the

microtubule organizing center (MTOC),

splits into two and each half begins to move to

opposite poles of the cell. The

mitotic spindle

(microtubules) forms between the centro-

somes.

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2. Prometaphase.

The nuclear envelope is disrupted, which allows the microtubules access

to the chromosomes. The nucleolus disappears. The

kinetochores

(protein complexes)

assemble at each centromere on the chromosomes. Certain microtubules of the mitotic
spindle bind to the kinetochores and are called

kinetochore microtubules

Other micro-

tubules of the mitotic spindle are now called

polar microtubules

and

astral microtubules

3. Metaphase.

The chromosomes align at the metaphase plate. The cells can be arrested in

this stage by microtubule inhibitors (e.g., colchicine). The cells arrested in this stage can
be used for

karyotype analysis

4. Anaphase.

The centromeres split, the kinetochores separate, and the chromosomes move

to opposite poles. The kinetochore microtubules shorten. The polar microtubules
lengthen.

5. Telophase.

The chromosomes begin to decondense to form chromatin. The nuclear enve-

lope re-forms. The nucleolus reappears. The kinetochore microtubules disappear. The
polar microtubules continue to lengthen.

6. Cytokinesis.

The cytoplasm divides by a process called

cleavage

cleavage furrow

forms

around the middle of the cell. A

contractile ring

consisting of actin and myosin filaments is

found at the cleavage furrow.

II. CHECKPOINTS

The checkpoints in the cell cycle are specialized signaling mechanisms that regulate and
coordinate the cell response to

DNA damage

and

replication fork blockage.

■

When the extent of DNA damage or replication fork blockage is beyond the steady-state
threshold of DNA repair pathways, a checkpoint signal is produced and a checkpoint is
activated.

■

The activation of a checkpoint slows down the cell cycle so that DNA repair may occur
and/or blocked replication forks can be recovered.

The two main protein families that control the cell cycle are

cyclins

and the

cyclin-dependent

protein kinases (Cdks).

■

A cyclin is a protein that regulates the activity of Cdks and is named because cyclins
undergo a cycle of synthesis and degradation during the cell cycle.

■

The cyclins and Cdks form complexes called

Cdk-cyclin complexes.

■

The ability of Cdks to phosphorylate target proteins is dependent on the particular
cyclin that complexes with it.

III. MEIOSIS

(Figure 9-2)

■

Meiosis is the process of

germ cell division

(contrasted with mitosis which is

somatic cell

division

) that occurs only in the production of the germ cells (i.e., sperm in the testes and

oocyte in the ovary).

■

In general, meiosis consists of two cell divisions (meiosis I and meiosis II) but only one
round of DNA replication that results in the formation of four gametes, each containing
half the number of chromosomes (23 chromosomes) and half the amount of DNA (1N)
found in normal somatic cells (46 chromosomes, 2N).

■

The various aspects of meiosis compared to mitosis are given in Table 9-1.

A. Meiosis I.

Events that occur during meiosis I include:

1. DNA replication
2. Synapsis.

Synapsis refers to the pairing of each duplicated chromosome with its homo-

logue, which occurs only in meiosis I (not meiosis II or mitosis).

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In female meiosis, each chromosome has a homologous partner so the two X chromo-
somes synapse and crossover just like the other pairs of homologous chromosomes.

In male meiosis, there is a problem because the X and Y chromosomes are very differ-
ent. However, the X and Y chromosomes do pair and crossover. The pairing of the X and
Y chromosomes is in an

end-to-end fashion

(rather than along the whole length as for all

the other chromosomes), which is made possible by a 2.6 Mb region of sequence
homology between the X and Y chromosomes at the tips of their p arms where
crossover occurs. This region of homology is called the

pseudoautosomal region

Although the X and Y chromosomes are not homologs, they are functionally homolo-
gous in meiosis so there are 23 homologous pairs of the 46 duplicated chromosomes in
the cell at this point.

3. Crossover.

Crossover refers to the

equal exchange

of large segments of DNA between the

maternal chromatid and paternal chromatid (i.e., nonsister chromatids) at the

chiasma

which occurs during prophase (pachytene stage) of meiosis I. Chiasma is the location
where crossover occurs forming an X-shaped chromosome and named for the Greek let-
ter chi, which also is X-shaped.

Crossover introduces

one level of genetic variability

among the gametes.

During crossover, two other events (i.e.,

unequal crossover

and

unequal sister chromatid

exchange

) may occur, which introduces

variable number tandem repeat (VNTR) polymor-

phisms, duplications, or deletions

into the human nuclear genome.

4. Alignment.

Alignment refers to the process whereby homologous duplicated chromo-

somes align at the metaphase plate. At this stage, there are still 23 pairs of the 46 chromo-
somes in the cell.

5. Disjunction.

Disjunction refers to the separation of the 46 maternal and paternal dupli-

cated chromosomes in the 23 homologous pairs from each other into separate secondary
gametocytes (Note: the

centromeres do not split

The choice of which maternal or paternal homologous duplicated chromosomes
enters the secondary gametocyte is a

random distribution

There are

(or 8.4 million)

possible ways the maternal and paternal homologous dupli-

cated chromosomes can be combined. This random distribution of maternal and
paternal homologous duplicated chromosomes introduces

another level of genetic vari-

ability

among the gametes.

6. Cell division.

Meiosis I is often called the

reduction division,

because the number of chro-

mosomes is reduced by half, to the haploid (23 duplicated chromosomes, 2N DNA con-
tent) number in the two secondary gametocytes that are formed.

B. Meiosis II.

Events that occur during meiosis II include:

1. Synapsis:

absent.

2. Crossover:

absent.

3. Alignment

23 duplicated chromosomes align at the metaphase plate.

4. Disjunction

23 duplicated chromosomes separate to form 23 single chromosomes when

the

centromeres split.

5. Cell division

gametes (23 single chromosomes, 1N) are formed.

IV. OOGENESIS: FEMALE GAMETOGENESIS

A. Primordial germ cells (46,2N)

from the wall of the yolk sac arrive in the ovary at

week 4

and dif-

ferentiate into

oogonia (46,2N)

which populate the ovary through mitotic division.

Oogonia enter meiosis I and undergo DNA replication to form

primary oocytes (46,4N).

All pri-

mary oocytes are formed by the

month 5 of fetal life.

No oogonia are present at birth. Primary

oocytes remain

dormant in prophase (diplotene) of meiosis I

from month 5 of fetal life until

puberty at

12 years of age (or ovulation at 50 years of age, given that some primary oocytes

will remain dormant until menopause).

Chapter 9

Mitosis, Meiosis, and Gametogenesis

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After puberty, 5 to 15 primary oocytes will begin maturation with each ovarian cycle, with
usually only one reaching full maturity in each cycle.

During the ovarian cycle, a primary oocyte completes meiosis I to form two daughter cells:
the

secondary oocyte (23 chromosomes, 2N amount of DNA)

and the

first polar body,

which

degenerates.

The secondary oocyte promptly begins meiosis II but is

arrested in metaphase of meiosis II

about 3 hours before ovulation. The secondary oocyte remains arrested in metaphase of
meiosis II until fertilization occurs.

At fertilization, the secondary oocyte will complete

meiosis II to form a

one mature oocyte (23,1N)

and a

second polar body

V. SPERMATOGENESIS: MALE GAMETOGENESIS IS CLASSICALLY

DIVIDED INTO 3 PHASES

A. Spermatocytogenesis. Primordial germ cells (46,2N)

form the wall of the yolk sac, arrive in the

testes at

week 4,

and remain

dormant until puberty

At puberty, primordial germ cells differen-

tiate into

Type A spermatogonia (46,2N).

Type A spermatogonia undergo mitosis to provide a

continuous supply of stem cells throughout the reproductive life of the male. Some Type A
spermatogonia differentiate into

Type B spermatogonia (46,2N)

B. Meiosis.

Type B spermatogonia enter meiosis I and undergo DNA replication to form

primary

spermatocytes

(46,4N). Primary spermatocytes complete meiosis I to form

secondary sperma-

tocytes (23,2N).

Secondary spermatocytes complete meiosis II to form

four spermatids (23,1N).

C. Spermiogenesis.

Spermatids undergo a

postmeiotic series of morphological changes

to form

sperm (23,1N).

These changes include formation of the acrosome; condensation of the

nucleus; and formation of head, neck, and tail.

The total time of sperm formation (from spermatogonia to spermatozoa) is about 64 days.

Newly ejaculated sperm are incapable of fertilization until they undergo

capacitation

which occurs in the female reproductive tract and involves the unmasking of sperm gly-
cosyltransferases and removal of proteins coating the surface of the sperm. Capacitation
occurs before the acrosome reaction.

VI. COMPARISON TABLE OF MEIOSIS AND MITOSIS

(Table 9-1)

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