CHROMOSOME; CELL CYCLE;

MITOSIS and MEIOSIS

GENETIKA (BIO 3041)

TA 2012/2013

Dr. Niken Satuti Nur Handayani, M.Sc

Laboratorium Genetika, Fakultas Biologi UGM
niken_satuti@ugm.ac.id./nikensat@yahoo.com
 Reference:
Genetics: From Genes to Genomes

Second Edition, 2000

Hartwell Hood Goldberg Reynolds Silver Veres
The Prokaryotic Chromosome
 The bacterial genome is composed of
one circular chromosome

4-5 Mb long
Condenses by
supercoiling and looping
into a densely packed
nucleoid body
Chromosomes replicate
inside cell and cell divides
by binary fission
The Eukaryotic Chromosome

An Organelle for Packaging and

managing DNA

Each chromosome packages a single

long molecule of DNA
Centromere structure and function
Chromosome

Each chromosome has a

constriction point called the
centromere, which divides the
chromosome into two sections,
or arms.
The short arm of the
chromosome is labeled the p
arm. The long arm of the
chromosome is labeled the q
arm.
 Characteristic shapes of
chromosomes
Short arm

Long arm

The location of the centromere on each chromosome gives the

chromosome its characteristic shape, and can be used to help
describe the location of specific genes.
Nilai Indeks Sentromer

Bentuk kromosom Nilai Indeks Sentromer (NIS)

p
x 100
p+q

p = panjang lengan pendek kromosom

q = panjang lengan panjang kromosom
p+q = panjang absolut kromosom
Nilai Indeks Sentromer

Posisi Bentuk Kromosom Simbol Rata-rata

Sentromer Kromosom NIS
Median Metasentris m 38 -50

Sub Median Sub Metasentris sm 26 - 37

Sub Terminal Akrosentris / st 13 - 25

Sub Telosentris
Terminal Telosentris t 0 - 12
Karyotype

A display of the paired homologues

chromosomes from a cell

Allows determination of:

sex of an individual,
abnormal chromosome number,
other chromosome abnormalities,
etc.
A closer look at karyotypes:
fully compacted metaphase chromosomes have unique,
reproducible banding patterns

Banding patterns
are highly
reproducible
A closer look at karyotypes:
fully compacted metaphase chromosomes have
unique, reproducible banding patterns.

Banding
patterns help
locate genes
Protein components of Chromosomes

Histone proteins abound the chromatin of all

eukaryotic cells
Histones small proteins with basic, positively charged amino
acids lysine and arginine
Bind to and neutralize negatively charged DNA
Make up half of all chromatin protein by weight
Five types: H1, H2A, H2B, H3, and H4
Core histones make up nucleosome: H2A, H2B, H3, and H4
DNA and histone synthesis regulation correlate timing so both are
synthesized together
High level of similarity of histones among diverse organisms
 Protein components of DNA
Nonhistone proteins are a heterogeneous group
Half of proteins in chromatin are nonhistone

Large variety of nonhistone proteins 200 2,000,000 in

diploid genomes
Large variety of functions
Scaffold backbone of chromosome
DNA replications e.g., DNA polymerases
Chromosome segregation e.g., motor proteins of kinetichores
Transcriptional regulation largest group regulates transcription
during gene expression
Occur in different amounts in different tissues because of
variety of function
 Packaging DNA
Histone
octamer

Histone proteins

B DNA Helix
 Packaging DNA

Histone
octamer

Histone proteins

B DNA Helix
 Packaging DNA

Histone
octamer

Histone proteins Nucleosome

B DNA Helix
Packaging DNA
Packaging DNA
 Packaging DNA

Beads on string

Looped
Tight helical Domains
fiber

Protein scaffold
 Packaging DNA

Nucleosomes
Metaphase
Chromosome

Tight helical fiber Looped Domains

Protein scaffold
B DNA Helix
The nucleosome:
The fundamental unit of chromosomal packaging
arises from DNAs association with histones

Chromatin fibers with

beads having diameter
of about 100 A and
strings having diameter
of 20 A
The nucleosome:
The fundamental unit of chromosomal packaging
arises from DNAs association with histones

Bead is a nucleosome
with about 160 bp of
DNA wrapped twice
around a core of 8
histones
40 bp of DNA link
together nucleosomes
The nucleosome:
the fundamental unit of chromosomal packaging
arises from DNAs association with histones

X-ray diffraction analysis

DNA does not coil smoothly

Base sequences dictate

preferred nucleosome
positions along DNA
Spacing and structure affect
genetic function
The nucleosome:
The fundamental unit of chromosomal packaging arises
from DNAs association with histones

Spacing of nucleosomes affects gene expression

Regions between nucleosomes available for
interactions with proteins involved in expression,
regulation, and further compaction
Determines how and whether certain proteins
interact with specific sequences
Packaging into nucleosomes condenses DNA
sevenfold
2 meters of DNA shortens to less than 0.25
meters
Models of higher level compaction seek to
explain extreme compaction of chromosomes at
mitosis

Formation of 300 A fiber through supercoiling

Models of higher level compaction seek to
explain extreme compaction of chromosomes at
mitosis

Radial loop-scaffold
model for higher levels of
compaction
Each loop contains 60-
100 kb of DNA
tethered by nonhistone
scaffold proteins
Radial loop-scaffold model
The Chromosome Theory of
Inheritance
Outline of Chromosome Theory of
Inheritance
Observations and experiments that placed the
hereditary material in the nucleus on the
chromosomes
Mitosis ensures that every cell in an organism
carries same set of chromosomes
Meiosis distributes one member of each
chromosome pair to gamete cells
Gametogenesis, the process by which germ
cells differentiate into gametes
Validation of the chromosome theory of
inheritance
Evidence that Genes Reside in the
Nucleus

1667 Anton van Leeuwenhoek

Microscopist
Semen contains spermatozoa (sperm animals)
Hypothesized that sperm enter egg to achieve fertilization
1854-1874 confirmation of fertilization through
union of eggs and sperm
Recorded frog and sea urchin fertilization using
microscopy and time-lapse drawings and micrographs
Evidence that Genes Reside in
Chromosomes
1880s innovations in microscopy and staining
techniques identified thread-like structures
Provided a means to follow movement of
chromosomes during cell division
Mitosis two daughter cells contained same
number of chromosomes as parent cell (somatic
cells)
Meiosis daughter cells contained half the
number of chromosomes as the parents (sperm
and eggs)
One Chromosome Pair Determines an
Individuals Sex

Walter Sutton Studied great lubber

grasshopper
Parent cells contained 22 chromosomes plus an
X and a Y chromosome
Daughter cells contained 11 chromosomes and
X or Y in equal numbers
 After
fertilization
Cells with XX
were females
Cells with XY
were males

Great lubber grasshopper

(Brachystola magna)
 Sex chromosome
Provide basis for
sex determination
One sex has
matching pair
Other sex has one
of each type of
chromosome
Photomicrograph of human
X and Y chromosome
 Sex
determination in
humans
Children receive
only an X
chromosome
from mother but
X or Y from
father
At Fertilization, Haploid Gametes
Produce Diploid Zygotes

Gamete contains one-half the number of

chromosomes as the zygote
Haploid cells that carry only a single
chromosome set
Diploid cells that carry two matching
chromosome sets
n the number of chromosomes in a haploid
cell
2n the number of chromosomes in a diploid
cell
 diploid vs
haploid cell in
Drosophila
melanogaster
Homologous chromosomes match in
size, shape, and banding patterns

Homologous chromosomes (homologs)

contain the same set of genes
Genes may carry different alleles
Non-homologous chromosomes carry
completely unrelated sets of genes
The Cell Cycle

The cell cycle is an orderly sequence of events

that occurs from the time when a cell is first
formed until it divides into two new cells.

Most of the cell cycle is spent in interphase.

Following interphase, the mitotic stage of cell

division occurs.
The cell cycle
Cell division increases the number of somatic (body)
cells, and consists of:

Mitosis (division of nucleus)

Cytokinesis (division of cytoplasm)

Apoptosis (cell death) decreases the number of cells.

Both cell division and apoptosis occur during normal

development and growth.
The number and shape of chromosomes
vary from species to species

Organism n 2n
Drosophila melanogaster 4 8
Drosophila obscura 5 10
Drosophila virilus 6 12
Peas 7 14
Macaroni wheat 14 28
Giant sequoia trees 11 22
Ophioglossum reticulatum (fern) 630 1260
Dogs 39 78
Humans 23 46
A closer look at karyotypes:
fully compacted metaphase chromosomes have
unique, reproducible banding patterns

Banding patterns can be

used to analyze
chromosomal differences
between species
Can also be used to
reveal cause of genetic
disease
e.g., Downs syndrome 3
copies of chromosome 21
 Maintaining the Chromosome
Number
When a eukaryotic cell is not dividing, the DNA and
associated proteins is a tangled (=kusut) mass of thin
threads called chromatin.

At the time of cell division, the chromatin condenses

to form highly compacted structures called
chromosomes.

Each species has a characteristic number of

chromosomes.
 Anatomy of a chromosome

Metaphase chromosomes are classified by the position of the centromere

Mitosis ensures that every cell in an organism
carries the same chromosomes

Cell cycle repeating pattern of cell growth and division

Alternates between interphase and mitosis

Interphase period of cell cycle between divisions/cells

grow and replicate chromosomes
G1 gap phase birth of cell to onset of chromosome
replication/cell growth
S synthesis phase duplication of DNA

G2 gap phase end of chromosome replication to

onset of mitosis
The cell cycle
Chromosome replication during
S phase of cell cycle

Synthesis of
chromosomes

Note the
formation of
sister
chromatids
Interphase

Within nucleus
G1, S, and G2 phase cell growth, protein synthesis,
chromosome replication
Outside of nucleus
Formation of microtubules radiating out into
cytoplasm crucial for interphase processes
Centrosome organizing center for microtubules located
near nuclear envelope
Centrioles pair of small darkly stained bodies at center of
centrosome in animals (not found in plants)
Mitosis Sister chromatids separate

Prophase chromosomes condense

Inside nucleus
Chromosomes condense into structures suitable for replication
Nucleoli begin to break down and disappear
Outside nucleus
Centrosomes which replicated during interphase move apart and
migrate to opposite ends of the nucleus
Interphase microtubules disappear and are replaced by microtubules
that rapidly grow from and contract back to centrosomal organizing
centers
 Mitosis - continued

Prometaphase
Nuclear envelope breaks down
Microtubules invade nucleus
Chromosomes attach to microtubules through kinetochore
Mitotic spindle composed of three types of microtubules
Kinetochore microtubules centrosome to kinetochore
Polar microtubules centrosome to middle of cell
Astral microtubules centrosome to cells periphery
 Mitosis - continued

Metaphase middle stage

Chromosomes move towards imaginary equator
called metaphase plate

Fig. 4.8 c
Mitosis - continued

Anaphase
Separation of sister chromatids allows each
chromatid to be pulled towards spindle pole
connected to by kinetochore microtubule
Mitosis continued

Telophase
Spindle fibers disperse
Nuclear envelope forms around group of chromosomes at each pole
One or more nucleoli reappear
Chromosomes decondense
Mitosis complete
Mitosis - continued

Cytokinesis - cytoplasm divides

Starts during anaphase and ends in telophase
Animal cells contractile ring pinches cells into two
halves
Plant cells cell plate forms dividing cell into two
halves
Actomyosin
contractile ring
Cell Division in Prokaryotes

The process of asexual reproduction in

prokaryotes is called binary fission.

The two daughter cells are identical to the

original parent cell, each with a single
chromosome.

Following DNA replication, the two resulting

chromosomes separate as the cell elongates.
The normal cell division

Cyclin-dependent
kinases collaborate
with cyclins to ensure
the proper timing and
sequence of cell-
cycle events
The cell cycle has
four phases: G1, S G2,
and M
Cell Cycle Checkpoints
In addition to growth and development,
interphase includes several checkpoints,
which regulate the cell cycle by allowing or
prohibiting the cells division.
These checkpoints, ensure that all cellular
components are present and in good
working order before the cell proceeds to
the next stage.
Cell Cycle Checkpoints
Checkpoints prevent cells with damaged
or missing chromosomes from
proliferating.
Defects in checkpoints can lead to
unregulated cell growth, as is seen in
some cancers.
G1/S checkpoint
Holds the cell in G1 until the cell has all of the
enzymes necessary for the replication of DNA.
After this checkpoint has been passed, the cell is
committed to divide.
After the G1/S checkpoint has been passed, DNA
synthesis must take place before the cell can proceed
to mitosis. If DNA synthesis is blocked (by drugs or by
a mutation), the cell will not be able to undergo
mitosis.
G2/M checkpoint
This checkpoint is passed only if the cells DNA
is undamaged.
Damaged DNA can inhibit the activation of some
proteins that are necessary for mitosis to take
place.
After the G2/M checkpoint has been passed, the
cell is ready to divide and enters the M phase.
MEIOSIS
Meiosis produces haploid germ cells

Somatic cells divide mitotically and make

up vast majority of organisms tissues
Germ cells specialized role in the
production of gametes
Arise during embryonic development in
animals and floral development in plants
Undergo meiosis to produce haploid gametes
Gametes unite with gamete from opposite sex
to produce diploid offspring
Meiosis Prophase I
Synapsis
Each synapsed chromosome pair is
known as a bivalent (because it
encompasses two chromosomes), or a
tetrad (because it contains four
chromatids).
On one side of the bivalent is a maternally
derived chromosome, on the other side a
paternally derived one.
Synapsis
Because X and Y chromosomes are not
identical, they do not synapse completely;
there is, however, a small region of
similarity (or homology) between the X
and the Y chromosomes that allows for a
limited amount of pairing.
Meiosis Prophase I continued
Meiosis I Metaphase and Anaphase
Meiosis Telophase I and Interkinesis
Meiosis
Prophase II and Metaphase II
Meiosis
Anaphase II and Telophase II
Meiosis - Cytokenesis
Meiosis contributes to genetic
diversity in two ways

Independent assortment of non-homologous

chromosomes creates different
combinations of alleles among
chromosomes
Crossing-over between homologous
chromosomes creates different
combinations of alleles within each
chromosome
Meiosis
Meiosis, which reduces the number of
chromosome sets from diploid to haploid,
is necessary to maintain the normal
chromosome number when two cells join
during sexual reproduction.
Meiosis helps to increase genetic variation
among offspring .
Gametogenesis involved mitosis
and meiosis

Oogenesis egg formation in humans

Diploid germ cells called oogonia multiply by mitosis
to produce primary oocytes
Primary oocytes undergo meiosis I to produce one
secondary oocyte and one small polar body (which
arrests development)
Secondary oocyte undergoes meiosis II to produce
one ovum and one small polar body
Polar bodies disintegrate (=hancur) leaving one large
functional gamete
Oogenesis in humans
Gametogenesis

Spermatogenesis in humans
Symmetrical meiotic divisions produce four functional
sperm
Begins in male testis in germ cells called
spermatogonia
Mitosis produces diploid primary spermatocytes
Meiosis I produces two secondary spermatocytes per
cell
Meiosis II produces four equivalent spermatids
Spematids mature into functional sperm
Spermatogenesis in humans
Meiosis
Chromosomes replicate once
Nuclei divide twice
Comparison of Meiosis with Mitosis

Before mitosis and meiosis, DNA replication occurs

only once during the interphase prior to cell
division.

Mitosis requires one division

Meiosis requires two divisions.

Two diploid daughter cells result from mitosis

Four haploid daughter cells result from meiosis.
Comparison of Meiosis with Mitosis

Daughter cells from mitosis are genetically

identical to parental cells

Daughter cells from meiosis are not genetically

identical to parental cells.

Mitosis occurs in all somatic cells for growth

and repair.

Meiosis occurs only in the reproductive organs

for the production of gametes.
Comparison of Meiosis I with Mitosis

Meiosis I: Mitosis:
Prophase I - pairing of Prophase has no such
homologous pairing
chromosomes
Metaphase
Metaphase I
homologous pairs line chromosomes align at
up at metaphase plate metaphase plate
Anaphase I Anaphase sister
homologous chromatids separate
chromosomes separate Telophase diploid cells
Telophase I daughter
cells are haploid
Comparison of Meiosis II with Mitosis

The events of meiosis II are like those of mitosis except

in meiosis II, the nuclei contain the haploid number of
chromosomes.

At the end of telophase II of meiosis II, there are four

haploid daughter cells that are not genetically identical.

At the end of mitosis, there are two diploid daughter cells

that are identical.
 The chromosome theory correlates Mendels
laws with chromosome behavior during meiosis
Chromosome Behavior
Each cell contains two copies of
each chromosome
Chromosome complements appear
unchanged during transmission from
parent to offspring
Homologous chromosomes pair and
then separate to different gametes
Maternal and paternal copies of
chromosome pairs separate without
regard to the assortment of other
homologous chromosome pairs
At fertilization an eggs set of
chromosomes unite with randomly
encountered sperms chromosomes
In all cells derived from a fertilized
egg, one half of chromosomes are
of maternal origin, and half are
paternal
Behavior of genes
Each cell contains two copies of
each gene
Genes appear unchanged during
transmission from parent to offspring
Alternative alleles segregate to
different gametes
Alternative alleles of unrelated
genes assort independently
Alleles obtained from one parent
unite at random with those from
another parent
In all cells derived from a fertilized
gamete, one half of genes are of
maternal origin, and half are paternal
Specific traits are transmitted with
specific chromosomes

A test of the chromosome theory.

If genes are on specific chromosomes, then traits
determined by the gene should be transmitted with
the chromosome
T.H. Morgans experiments demonstrating sex-linked
inheritance of a gene determining eye-color
demonstrate the transmission of traits with
chromosomes
1910 T.H. Morgan discovered a white eyed male
Drosophila melanogaster among his stocks
The genetic information of an individual
is contained in 23 pairs of chromosomes
Every human cell contains the 23 pairs of
chromosomes
One pair is called sex chromosomes
Male : XY
Female: XX
Other 22 pairs of homologous chromosomes
are called autosomes
Two chromosomes in the same pair are called
homologous chromosomes.
Group Discussion
A length of double stranded DNA
contains 120 nucleotides and codes for
polypeptide X. What is the maximum
length of polypeptide X? Explain your
answer.
Briefly describe three different processes
that occur during a sexual life cycle
increase the genetic diversity of offspring.
Answer
1. 20 amino acids
2. a. Various orientations of chromosomes at metaphase I
of meiosis lead to different combinations of
chromosomes in gametes (sperms and ova)
b. Random fertilization of eggs by sperm further
increases possibilities for variation in offspring.
c. Crossing over during prophase I results in an
exchange of chromosome segments and new
combinations of genes.
3. D
 Chromatin fibers include .
a) DNA and structural polysaccharides
b) RNA and phospholipids
c) protein and carbohydrate
d) DNA and protein
e) triacylglycerol and steroids
 A nucleosome consists of
(a) DNA and scaffolding proteins
(b) scaffolding proteins and histones
(c) DNA and histones
(d) DNA, histones, and scaffolding proteins
(e) histones only
At which of the following stages do human skin
cell nuclei have the same DNA content?
(a) early mitotic prophase and late mitotic telophase
(b) G1 and G2
(c) G1 and early mitotic prophase
(d) G1 and late mitotic telophase
(e) G2 and late mitotic telophase
Which of the following are genetically identical?
(a) two cells resulting from meiosis I
(b) two cells resulting from meiosis II
(c) four cells resulting from meiosis I followed
by meiosis II
(d) two cells resulting from a mitotic division
(e) all of the preceding
The life cycle of a sexually reproducing
organism includes ..
(a) mitosis
(b) meiosis
(c) fusion of sex cells
(d) b and c
(e) a, b, and c