BIO 2, Lecture 9BIO 2, Lecture 9BIO 2, Lecture 9BIO 2, Lecture 9REPRODUCTION I:REPRODUCTION I:

ASEXUAL REPRODUCTION: ASEXUAL REPRODUCTION: BINARY FISSION, MITOSIS, AND THE BINARY FISSION, MITOSIS, AND THE

CELL CYCLECELL CYCLE

• All living organisms replicate their DNA (imperfectly) and then pass it on to “daughter cells” through cell division, a process called reproduction

• Because replication is imperfect, daughter cells will contain new mutations

• These mutations are then subject to increasing or decreasing in frequency in the population due to natural selection and other forces that drive evolution

• There are two types of reproduction: asexual and sexual• All living organisms contain at least some

cells that reproduce asexually

• Some living organisms also contain specialized cells that reproduce sexually

• Asexual reproduction is nature’s way of cloning a cell• The two daughter cells produced by

asexual reproduction are genetically identical to the parent cell (except for rare mutations)

100 µm

(a) Asexual Reproduction : Produces 2 daughter cells genetically identical to the original parent cell

• Sexual reproduction is nature’s way of producing genetically diverse daughter cells• Four daughter cells (eggs or sperm) are

produced by sexual reproduction that each contain exactly half the genetic material of the parent cell and are genetically different from the parent cell and from each other

• This lecture will focus on asexual reproduction

• The next lecture will focus on sexual reproduction

• Asexual reproduction comes in two forms: binary fission and mitosis

• Binary fission is used by prokaryotes to distribute the duplicated copies of their single circular chromosome to two daughter cells

• Because prokaryotes are single-celled organisms, binary fission asexually reproduces not only the cell but also the entire organism

Origin ofreplication

Two copiesof origin

E. coli cell Bacterialchromosome

Plasmamembrane

Cell wall

Origin Origin

• Mitosis is used by eukaryotic organisms, which have multiple linear chromosomes, and is a much more complex process than binary fission

• Some single-celled eukaryotes use mitosis as the primary method of reproducing the whole organism (e.g. yeast)

• Most, however, use it for growth and replacement of dead cells and reproduce the whole organism by sexual reproduction

Yeast cells reproducing the whole organism

(cell) asexually by mitosis

Human white blood cell

reproducing asexually by

mitosis

• To understand mitosis, it is necessary to first look at the eukaryotic cell cycle

• In preparation for cell division, DNA is replicated and the chromosomes condense

• Each duplicated chromosome has two sister chromatids, which separate during cell division

• The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached

0.5 µm Chromosomes

Chromosomeduplication(including DNAsynthesis)

Chromo-some arm

Centromere

Sisterchromatids

DNA molecules

Separation ofsister chromatids

Centromere

Sister chromatids

• In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis (cell division following mitosis)

• Using these dyes, it was possible to divide the cell cycle into two phases:– Mitotic (M) phase (mitosis and

cytokinesis), at which time chromosomes are visible

– Interphase (cell growth and copying of chromosomes in preparation for cell division), at which time chromosomes are not visible

• Interphase (about 90% of the cell cycle) can be divided into sub-phases:

– G1 phase (“first gap”)

– S phase (“synthesis”)– G2 phase (“second gap”)

• The cell grows and performs its ceullar functions during all three phases, but chromosomes are duplicated only during the S phase

S(DNA synthesis)

MITOTIC(M) PHASE

Mitos

is

Cytokin

esis

G1

G2

• Mitosis is conventionally divided into five phases:– Prophase– Prometaphase

– Metaphase– Anaphase– Telophase

• Cytokinesis is well underway by late telophase

PrometaphaseProphaseG2 of Interphase

Nonkinetochoremicrotubules

Fragmentsof nuclearenvelope

Aster CentromereEarly mitoticspindle

Chromatin(duplicated)

Centrosomes(with centriolepairs)

Nucleolus Nuclearenvelope

Plasmamembrane

Chromosome, consistingof two sister chromatids

Kinetochore Kinetochoremicrotubule

Metaphase Anaphase Telophase and Cytokinesis

Cleavagefurrow

Nucleolusforming

Metaphaseplate

Centrosome atone spindle pole

SpindleDaughterchromosomes

Nuclearenvelopeforming

• The mitotic spindle is an apparatus of microtubules (long cytoplasmic motor proteins) that controls chromosome movement during mitosis

• During prophase, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center• The centrosome replicates, forming two

centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them

• During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes to the center of the cell• Kinetochores are centromeres bound by

proteins that attract the microtubules

• At metaphase, the chromosomes are all lined up at the metaphase plate, the midway point between the spindle’s two poles

Microtubules Chromosomes

Sisterchromatids

Metaphaseplate

Centrosome

Kineto-chores

Kinetochoremicrotubules

Overlappingnonkinetochoremicrotubules

Centrosome 1 µm

0.5 µm

• In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell

• The microtubules shorten by depolymerizing at their kinetochore ends

EXPERIMENT

Kinetochore

RESULTS

CONCLUSION

Spindlepole

Mark

Chromosomemovement

Kinetochore

MicrotubuleMotorprotein

Chromosome

Tubulinsubunits

• In telophase, genetically identical daughter nuclei form at opposite ends of the cell

• In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow

• In plant cells, a cell plate forms during cytokinesis

Cleavage furrow100 µm

Contractile ring ofmicrofilaments

Daughter cells

(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)

Vesiclesformingcell plate

Wall ofparent cell

Cell plate

Daughter cells

New cell wall

1 µm

Chromatincondensing

Metaphase Anaphase TelophasePrometaphase

Nucleus

Prophase1 2 3 54

Nucleolus Chromosomes Cell plate10 µm

• The frequency of cell division varies with the type of cell

• These cell cycle differences result from regulation at the molecular level

• The cell cycle appears to be driven by specific chemical signals present in the cytoplasm• Some evidence for this hypothesis comes

from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei

Experiment 1 Experiment 2

EXPERIMENT

RESULTS

S G1M G1

M MSS

When a cell in theS phase was fused with a cell in G1, the G1 nucleus immediatelyentered the Sphase—DNA was synthesized.

When a cell in theM phase was fused with a cell in G1, the G1 nucleus immediatelybegan mitosis—aspindle formed andchromatin condensed,even though thechromosome had notbeen duplicated.

• The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock

• The cell cycle control system is regulated by both internal and external controls

• The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received

• Accurate translation requires two steps:– 1. An enzyme called aminoacyl-tRNA

synthetase adds an amino acid to all the tRNAs that carry the anticodon that is complementary to the codon in the mRNA that codes for that amino acid

– 2. The tRNA anticodon recognizes and base-pairs to its mRNA codon

• Flexible pairing at the third base of a codon is called wobble and allows some tRNAs to bind to more than one codon

SG1

M checkpoint

G2M

Controlsystem

G1 checkpoint

G2 checkpoint

• For many cells, the G1 checkpoint seems to be the most important one

• If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide

• If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase

G1

G0

G1 checkpoint

(a)Cell receives a go-ahead signal

G1

(b) Cell does not receive a go-ahead signal

• An example of an internal signal that stops the cell cycle: Kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase

• Some external signals that promote the cell cycle are growth factors, proteins released by certain cells that stimulate other cells to divide• For example, platelet-derived growth

factor (PDGF) stimulates the division of human fibroblast cells in culture

Petriplate

Scalpels

Cultured fibroblasts

Without PDGFcells fail to divide

With PDGFcells prolifer-ate

10 µm

• Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing

• Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide

Anchorage dependence

Density-dependent inhibition

Density-dependent inhibition

(a) Normal mammalian cells (b) Cancer cells25 µm25 µm

• Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence• Cancer cells do not respond normally to

the body’s control mechanisms• Cancer cells may not need growth factors

to grow and divide• They may make their own growth factor• They may convey a growth factor’s signal

without the presence of the growth factor• They may have an abnormal cell cycle

control system

• A normal cell is converted to a cancerous cell by a process called transformation

• Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue• If abnormal cells remain at the original

site, the lump is called a benign tumor

• Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors

Tumor

A tumor growsfrom a singlecancer cell.

Glandulartissue

Lymphvessel

Bloodvessel

Metastatictumor

Cancercell

Cancer cellsinvade neigh-boring tissue.

Cancer cells spreadto other parts ofthe body.

Cancer cells maysurvive andestablish a newtumor in anotherpart of the body.

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