Mitosis & Meiosis

Splitting up is complicated.
 Overview

• DNA replication
• Overview of cell division
• Mitosis
• Meiosis
DNA Replication
Occurs during interphase of
cell cycle

1 DNA molecule untwisted

Each parent strand serves

as template for new strand
= 2 new DNA molecules,
each ½ old & ½ new
= semi-conservative
replication
 Enzymes break H bonds
between 2 strands
= unwinds & exposes
nucleotide bases

Free nucleotides pair with

exposed bases

Each parent strand has new

one made on it
= twist together to form double
helix
DNA replication in a little more
detail …
Sugar-phosphate backbones of
2 DNA strands run in opposite
directions

5’ end
= Phosphate group on sugar’s C

3’ end
= –OH group on sugar’s C
 DNA polymerase adds nucleotides to 3’
ends only

Daughter strand grows in 5’ to 3’ direction

= 1 daughter strand
synthesized continuously

= Other daughter strand

synthesized disjointedly
 Replication Enzymes:
Helicases
Catalyze breaking of H bonds so double
helix can unwind

Work with small proteins to prevent

rewinding of parent strands
 Replication Enzymes:
DNA Polymerases
Catalyze addition of free nucleotides to
exposed bases on each strand

Also have proofreading abilities

 Replication Enzymes:
DNA Ligases
Work on discontinuously-assembled strand

Seal together short stretches of new

nucleotides
 Mistakes occur that can be lethal if not caught
e.g. wrong base-pairing

DNA proofreading mechanisms fix most

replication errors & breaks in strands
(proofread & correct mismatches)

Repair enzymes repair some changes by

snipping out damaged sites or mismatches

If mismatch can’t be fixed, replication is stopped

 Cell Division: An Overview
Parents reproduce to produce new
generation of cells or multicellular
organism

Offspring inherits all information & metabolic

machinery from parent
Prokaryotic Cell Division
Prokaryotic cells reproduce
asexually

= binary fission
 Eukaryotic Cell Division

DNA in eukaryotic cells is in nucleus

Eukaryotic cells can’t divide by fission

Must copy & package DNA into > 1

nucleus before cytoplasm can split
Two Types of Cell Division
Mitosis:
– Produces 2 genetically identical cells
– Happens throughout body

Meiosis:
– Produces 4 genetically different cells
– Cells only have ½ of genetic info
– Happens only in gonads
 Mitosis
One part of the cell cycle

Growth, cell replacement, tissue repair

Also used for asexual reproduction

= organisms clone selves

Unique to eukaryotes
 The Cell Cycle
The period from one cell division to next
Interphase: The Longest Phase

90% of cell cycle length

Interphase
G1: Gap / Growth Phase

Cell growth

# of cytoplasmic
components doubled
S: Synthesis Phase

DNA duplicated
Chromosome & copy = sister chromatids

Joined at centromere
 G2: Gap or Growth Phase II

Makes proteins
necessary for cell
division

Cell prepares to divide

 Cells stay in G1 if making
macromolecules

Enter S when DNA & accessory proteins

are copied

Rate of DNA replication is same for all cells

of a species
 Same cycle length for same type of cells

Different cycle lengths for different types of

cells
e.g. cells in red bone marrow divide every
second
e.g. nerve cells stay in G1 indefinitely

Rate of cell division is under control

(checkpoints, molecular brakes, etc.)
 After G2, cell enters mitosis

Mitosis maintains cell’s chromosome #

 Chromosome Number
Humans have 46
chromosomes

= diploid (2n)

2 of each type of
chromosome
= one set from mother, one
from father
 During mitosis:

Each 2n parent cell produces two 2n

daughter cells

Each daughter cell has each pair of

chromosomes
= 23 pairs
During mitosis, 2 sister chromatids (duplicated
chromosomes) separate

Each becomes independent chromosome that

ends up in 1 of daughter cells
 The Mitotic Spindle
Present in every cell

Made of microtubules
= change length by
addition or removal of
tubulin subunits

Originates from pair of

centrioles
 Early in cell division, duplicated
chromosome is condensed =
coils up

DNA winds twice around histones

= nucleosome

Keeps chromosomes organized

during nuclear division
Late Interphase / Pre-Prophase

Outside of nucleus, 2 centrioles

duplicate selves
Early Prophase

Inside nucleus:
Chromosomes begin to
condense

Outside nucleus:
Spindle begins to form

Nuclear envelope begins to

fall apart
Late Prophase

Nuclear envelope completely

falls apart

Spindle fibres from each pole

attach to sister chromatids of
each chromosome
Metaphase

Chromosomes line up halfway

between spindle poles
Anaphase
Sister chromatids of each
chromosome separate & move
to opposite poles
(motor proteins attached to
kinetochores drag chromatids
along microtubules)

Spindle poles pushed apart by

growing microtubules
Telophase
1 of each type of chromosome
reaches each spindle pole
= 2 identical groups of
chromosomes at each cell pole

Chromosomes decondense

Nuclear envelope forms around

each cluster of chromosomes
= two nuclei, each with 2n # of
chromosomes
 Cytokinesis

Cytoplasm of cell divides

Results in 2 daughter cells, each

with same number of
chromosomes as parent cell
Cytokinesis in Animal Cells
Contractile ring mechanism

Halfway between cell’s poles,

plasma membrane constricts
= cleavage furrow
(ATP energy causes contraction
of actin filaments)

Cleavage furrow deepens until

cytoplasm split into 2
 Cytokinesis in Plant Cells
Cell plate formation

Golgi vesicles move to cell

equator & fuse

Vesicle membranes
become cell membranes

Contents become cellulose

cell wall
 Summary of Mitosis

Nuclear & cellular division that maintains

chromosome #

Used for growth, repair, asexual

reproduction
Cell division & DNA replication regulated so
that:

DNA only replicated once before cell division

Cells that never divide do not replicate DNA

Cells don’t try to replicate DNA if lack the

energy & raw materials to complete process
Cellular Controls over Mitosis
Anchorage dependence
Animal cells must be in contact with a solid
surface to divide

Density-dependent inhibition
Crowded cells stop dividing

Growth factors
Required to start & continue dividing
Secreted by other cells
 Cell Cycle Checkpoints

Cell cycle has checkpoints:

– Structure of chromosomal DNA monitored
– Completion of phases monitored
– Determines if good time for cell division

Rely on internal & external cues

 G1 checkpoint is most important:

If no go-ahead signal, cell will switch to

non-dividing G0 phase

e.g. nerve & muscle cells remain in G0

indefinitely
 Cancer & Cell Division
If immune system doesn’t recognize &
destroy a cancerous cell, it may divide
multiple times & form a tumor

Benign
Cells remain localized

Malignant
Spreads to other parts of body & disrupts
function
Why don’t cancer cells follow the
rules?
Don’t exhibit density-dependence

Have defective control systems

Ignore / over-ride checkpoints

Some synthesize own growth factors so

continue dividing

Divide indefinitely
 Types of Cancers
Carcinomas
Internal & external coverings of body e.g.
skin

Sarcomas
Supportive tissues e.g. bone & muscle

Leukemias & Lymphomas

Blood-forming tissues e.g. bone marrow,
spleen, lymph nodes
 Ways to Treat Cancer
If not severe:

Surgical removal of tumor

Radiation therapy
(damages DNA of cancer cells to greater
degree than normal cells)
 If severe:

Chemotherapy
Uses drugs to disrupt cell division
e.g. Paclitaxel freezes the mitotic spindle at
metaphase
e.g. Vinblastin prevents spindle formation

Also affects rapidly-dividing normal cells e.g.

intestinal lining, immune cells, hair follicle cells
Cloning

Donor cells from 1

animal starved so
enter non-dividing
G0 phase

Nucleus removed
from unfertilized
egg cell of another
animal
Donor cell & egg cell placed next to each other
in culture dish & electrically stimulated
Cells fuse & enter mitosis
Cell continues mitotic divisions & forms embryo

Embryo implanted into surrogate mother

(same spp. as egg cell)

Surrogate mother gives birth to genetic twin of

“donor cell” animal
 Mitosis vs. Meiosis
Mitosis:
– Occurs in somatic cells
– Results in 2 genetically identical cells
– Growth, cell replacement, tissue repair
= asexual reproduction

Meiosis:
– Occurs in sex cells
– Results in 4 genetically different cells with ½
genetic info of parent cell
= sexual reproduction
Asexual vs. Sexual Reproduction

Asexual reproduction:
Individual makes multiple offspring with identical
DNA

Sexual reproduction:
Allows for variety in heritable traits
Adaptive in changing environments
Meiosis → formation of gametes → fertilization
The Eukaryotic Chromosome

Double-stranded DNA & associated proteins

Chromosomes duplicated during interphase

Unduplicated Duplicated

Centromere

Sister chromatids
 Chromosome Number

Almost every cell in body has 2 complete

sets of chromosomes

One set from mother, one from father

2 sets = diploid (2n)

Each cell has 2 versions of each gene

 Homologous chromosomes

Pair of chromosomes that carry genes for same

heritable traits

Except sex chromosomes (X or Y)

 Genes

Sequences of chromosomal DNA

Contain heritable information to make

new individuals

Individuals have pairs of genes on pairs

of chromosomes

Each member of pair of gene = allele

 Allele
One of the variant forms of a gene at a particular
(locus) location on a chromosome

Different alleles produce variation in inherited

characteristics (e.g. hair & eye colour, etc.)

Basis for evolution: endless combinations of alleles

lead to variations in traits
 So What is Meiosis?

Nuclear division that halves chromosome #

Occurs only in sex (reproductive) cells

1st step in formation of gametes ( or )

Gametes fuse with opposite sex gametes to

form new individual
 Humans are diploid (2n) with 46
chromosomes
(23 + 23 homologous chromosomes)

Meiosis halves chromosome number so

daughter cells (gametes) are haploid (n)
with 23 chromosomes
 Gametes

Have only 1 set of chromosomes

= haploid (n)

Each gamete has 1 allele for each gene

In humans = eggs or sperm

During meiosis, one cell goes through 2
divisions to end with formation of 4 cells,
all with haploid (n) nuclei
 Interphase

Same as in mitosis:

Cell grows & duplicates cytoplasmic

components

DNA is replicated
Prophase I

Chromosomes condense

Crossing-over occurs between

homologous chromosomes

Centrioles move to opposite

sides of nuclear envelope

Nuclear envelope begins to fall

apart
 Crossing Over

When chromosomes condense during

prophase, homologous chromosomes
stick very closely together & form a tetrad
Maternal & paternal chromosomes swap genes
= exchange segments of genetic info

Homologous chromosomes become mixture of

maternal & paternal info

chiasma
Metaphase I

Homologues of chromosomes
tethered by microtubules at
opposite spindle poles

Chromosomes line up along

equator of cell
Anaphase I

Chromosomes pulled apart &

move towards respective poles

Poles move further apart

 Telophase I

Cytoplasm divides

Results in 2 haploid cells

(only have 1 of each pair of
homologous chromosomes)

Chromosomes still duplicated

 Prophase II

New mitotic spindle forms in each cell

Chromatids of each chromosome

become tethered to opposite poles
Metaphase II

Chromosomes line up along

equator of cell
Anaphase II

Chromatids separate & move

towards opposite poles

Spindle poles pushed apart

 Telophase II

Nuclear envelope forms around each

chromosome cluster
 Cytokinesis
Cytoplasm divides

Results in 4 haploid (n) daughter cells

Chromosomes are unduplicated

 Meiosis—things to pay attention to:
1. DNA replication:
a. Occurs only during interphase before Meiosis I

2. Meiosis I
a. Prophase: crossing-over
b. Metaphase: line up in 2 rows
c. Anaphase: separation of homologous chromosomes

3. Meiosis II
a. Similar to mitosis but no interphase precedes it
b. Division results in haploid cells
 Meiosis & Trait Variation
Can occur via:

– Crossing over

– Random alignment of chromosomes at

metaphase I
 a. Crossing Over
Exchanges of allele-containing segments occurs
between non-sister chromatids (i.e. between
maternal & paternal chromosomes)

Gene-swapping: different versions of heritable

information are swapped
= leads to recombination of genes & variation in traits
b. Metaphase I Alignments
a.k.a random assortment

Duplicated chromosomes randomly tether

to spindle poles

i.e. no set rules for where maternal &

paternal chromosomes should be
positioned
 Which half of homologous chromosome pair
ends up at which pole is totally random

223 (8,388,608) possible combos of maternal &

paternal chromosomes!
From Gametes to Offspring

In animals, diploid germ cells become

gametes

Gametes differ from species to species

 Male Gamete Formation

Germ cell (spermatogonium) develops into

1° spermatocyte

Enters meiosis

Results in 4 haploid cells (spermatids) that

differentiate into sperm cells
Female Gamete Formation

Germ cell (oogonium) develops into 1°

oocyte (immature egg)

Grows in size

4 daughter cells differ in structure &

function
When 1° oocyte divides after meiosis I, one
daughter cell (2° oocyte) gets most of
cytoplasm

Other cell (1st polar body) is very small

After meiosis II, one of 2° oocyte’s daughter cells
is 2nd polar body (also very small)

Other gets most of cytoplasm and develops into

ovum (egg)

1st polar body’s daughter cells are both polar

bodies
 Polar bodies eventually degenerate
Sole function: to ensure ovum is haploid

Ovum gets most of cytoplasm & metabolic

machinery
Is able to support early cell divisions of new
individual after fertilization
Fertilization: When 2 Gametes
Become 1
Male & female gametes unite

Haploid nuclei fuse

Restores diploid nature of cells

(n + n = 2n)

↑ variation among offspring:

– Random gametes fusing
– Millions of possible chromosome combos in
each gamete
 Summary of Meiosis

Nuclear division that halves chromosome

number

Results in n male & female gametes that

can fuse during fertilization to produce 2n
offspring
Chromosomal Abnormalities
Abnormal chromosome structure:
Breakage of chromosome leads to
rearrangements that affect genes on that
chromosome

Abnormal chromosome number:

Chance events occur before or after cell
division that result in wrong chromosome #
Changes in Chromosome Structure

Can have neutral to harmful effects,

depending on type of chromosomal
change

4 types of rearrangement:
• Inversion
• Deletion
• Duplication
• Translocation
 (a) Inversions

Broken fragment reattaches to original

chromosome but in reverse direction

Genes still present in normal #, so less

harmful than other categories
 (b) Deletions
Fragment of chromosome is lost

Cause severe physical & mental problems

e.g. cri du chat
 (c) Duplications
Fragment from one chromosome joins to a
sister chromatid or homologous
chromosome

Can have severe effects

 (d) Translocations
Fragment of chromosome attaches to
non-homologous chromosome

May or may not be harmful

If chromosomal changes occur in sperm
or egg cells:
= may cause congenital disorders

If chromosomal changes occur in somatic

cells:
= can lead to development of cancer
(which is why cancer is generally not
heritable)
 Heritable Changes in
Chromosome #

Chance events occur before or after cell

division that result in wrong chromosome
#

Consequences can be minor or lethal

 Most changes in chromosome number
occur because of non-disjunction
= 1 pair of chromosomes do not separate
during mitosis or meiosis
 Aneuploidy:
Normal #  1 chromosome
e.g. trisomy 21 (Down Syndrome)

Polyploidy:
3n, 4n, etc.
Normal in many plants & animals
 # of sex chromosomes can also be
abnormal

E.g. XO, XXX, XXY, XYY

Will return to this when covering inheritance