Lecture 9

Lecture 9Cell Cycle, Cancer, Meiosis,

Patterns of InheritanceCovers

Cell Cycle/Cancer: 9.4, 9.6 & Ch 9 “Closer Look”Meiosis 9.10

Patterns 10.1, 10.3-10.8

Cell Reproduction: The Cell Cycle

• Cells reproduce by cell division: a PARENT cell gives rise to DAUGHTER cells.*– *: in Mitosis, two daughter cells are formed– *: in Meiosis, four daughter cells are formed

• Each DAUGHTER cell receives a complete set of hereditary information from the PARENT cell**– **: except in meiosis. In meiosis, daughter cells receive

only HALF of the hereditary information from the parent cell.

Cell Cycle divided into 2 phases*• Interphase

• Cell acquires nutrients from the environment• Cell grows• Cell differentiates (nerve cells will grow axons, liver cells will

produce bile)• Cell DUPLICATES ITS CHROMOSOMES (DNA Replication)• Most cells spend large majority of time in Interphase

• Cell Division– DUPLICATED CHROMOSOMES separate and move into each

daughter cell» Recall Prophase, Metaphase, Anaphase, Telophase

– Cytokinesis: division of cytoplasm

INTERPHASE MITOSIS

nuclearenvelope chromatin

nucleolus

centriolepairs

beginning ofspindle formation

kinetochore

kinetochoremicrotubules

spindle pole

spindle polecondensingchromosomes spindle

microtubules

(a) Late Interphase Duplicated chromosomes are in the relaxed uncondensed state; duplicated centrioles remain clustered.

(b) Early Prophase Chromosomes condense and shorten; spindle microtubules begin to form between separating centriole pairs.

(c) Late ProphaseThe nucleolus disappears; the nuclear envelope breaks down; some spindle microtubules attach to the kinetochore (blue) of each sister chromatid.

(d) MetaphaseKinetochore microtubules line up the chromosomesat the cell's equator.

Fig. 9-8a, b, c, d

Fig. 9-8e, f, g, h

INTERPHASE

chromosomesextending

nuclear envelopere-forming

nucleolusreappearing

(e) AnaphaseSister chromatids separate and move to opposite poles of the cell; polar microtubules push the poles apart.

(f) TelophaseOne set of chromosomes reaches each pole and begins to decondense; nuclear envelopes start to form; nucleoli begin to reappear; spindle microtubules begin to disappear; microfilaments form rings around the equator.

(g) CytokinesisThe ring of microfilaments contracts, dividing the cell in two; each daughter cell receives one nucleus and about half of the cytoplasm.

(h) Interphase of daughter cellsSpindles disappear,intact nuclear envelopes form, and the chromosomes extend completely.

polarmicrotubules

Control of Cell Cycle*

• Some proteins STIMULATE THE CELL CYCLE. Any gene whose protein product stimulates the cell cycle is called a PROTOONCOGENE.– Growth factors*, growth factor receptors, cyclin and cyclin kinases

• Some proteins act as intracellular “checkpoints” to STOP THE CELL CYCLE if problems occur:– Is parental DNA intact and ready to replicate?– Has DNA been replicated correctly?– Have chromosomes lined up correctly in metaphase?Any gene whose protein product stops cell division when

there are problems is called a TUMOR SUPPRESSOR GENE.

Growth Factors STIMULATE the Cell Cycle

• Binding to cell membrane of cell that it is stimulating (there must be a receptor protein on the surface of the cell to accept the growth factor)

• Growth factor binding to cell results in synthesis of cyclin inside the cell• Cyclin will then bind to Cyclin-dependent kinase: a type of enzyme that adds

a phosphate group to other proteins. • Cyclin/kinase complex will then add a phsophate group to Rb molecule

(which normally suppresses cell cycle), and this will stimulate synthesis and activity of proteins like DNA polymerase and other proteins that participate in the cell cycle

• Growth factors are MADE*– In response to cell damage or low levels of cells – At particular times in an organism’s lifetime (growth factors stimulate

brain cells and bone cells to stop/start at particular times during development.)

cyclin-dependentkinase (Cdk)

growth factorreceptor

cyclin

plasmamembrane

(cytoplasm)

(extracellularfluid)

Growth factorbinds to its receptor

Cyclin activatesCdk; active Cdkstimulates DNAreplication

Cyclin bindsto Cdk

Cyclins aresynthesized

growth

factor

1 2

4

3

Fig. 9-10

Cancer*

• Cancer develops when:– Protooncogene is mutated, CAUSING THAT

PROTEIN TO CONSTANTLY STIMULATE THE CELL CYCLE

– Tumor Supressor gene is mutated CAUSING THAT PROTEIN TO BE UNABLE TO STOP THE CELL CYCLE

Normal Protooncogene

Mutated Protooncogene= Oncogene

Normal Tumor Suppressor Gene

Mutated Tumor Supressor Gene

How do we get from a mutated gene to cancer?

• Our body has a way of killing “renegade” cells (those that “look” different than normal cells), but those that “slip through” will make daughter cells that also contain mutated genes. If left unchecked, cells reproduce unchecked and a tumor can develop– Benign tumor: too many cells but DNA is intact

(mutation of protooncogene)– Malignant tumor: too many cells, all with mutated

DNA (mutation of tumor suppressor gene)

Meiosis*• In order to make a new person, we need:

– An egg (gamete/sex cell)• With ½ of the material in a normal cell’s DNA (23

chromosomes)

– A sperm (gamete/sex cell)• With ½ of the material in a normal cell’s DNA (23

chromosomes)

• Sperm and egg unite in fertilization to create a zygote (with 46 chromosomes) that will become a person.

Some terms to understand Meiosis*

• Somatic Cells– Have 46 chromosomes (23 PAIRS)– In each pair of chromosomes, 1 chromosome

comes from mom, one from dad– Out of the 23 pairs, 22 pairs are AUTOSOMES and

1 pair are SEX chromosomes– Sex cells are made from somatic cells.

Some terms to understand Meiosis*

• Sex cells– Exist only in the sex organs (ovary/testes)– Have 23 UNPAIRED chromosomes– 22 single autosomes and 1 sex cell (X OR Y)

Some terms to understand Meiosis*

• Homologous Pairs: present in somatic cells only, homologous chromosomes are the same size and shape and CARRY THE SAME GENES, but can have different alleles.

• EX: Chromosome pair #1, #2, etc.• On Chromosome #1 is gene for eye color. You

can have a blue eye gene on one of your chromosomes and a brown eye gene on the other chromosome.

Homologous Chromosomes May Have the Same or Different Alleles

of Individual Genes

Fig. 9-12

gene 1 gene 2

same alleles different alleles

Meiosis

• Meiosis starts with a somatic cell.• There are 2 nuclear divisions: Meiosis I & Meiosis II• Meiosis I: DNA is copied, then HOMOLOGOUS PAIRS

SEPARATE. At end of Meiosis I, daughter cells will only have ONE of each homologous pair, but it will be a duplicated chromosome.

• Meiosis II: NO DNA REPLICATION. In each daughter cell, duplicated chromosomes separate into 2 daughter cells.

• End result is FOUR daughter cells (sperm/egg), each with 23 chromosomes.

sisterchromatids

homologouschromosomes

(c) After meiosis II(b) After meiosis I(a) Replicatedhomologuesprior to meiosis

Meiosis Is a Reduction Division That Halves the Number of

Chromosomes

Fig. 9-13

Events that enhance genetic diversity*

• Genetic variability is essential for survival, reproduction and evolution.

• Mutations result in genetic variability (creates alleles-alternate form of a gene) BUT there are other events that contribute to genetic diversity:– 1.) Shuffling of homologous chromosomes– 2.) Crossing over– 3.) Fusion of gametes at fertilization

1.) Shuffling of homologous chromosomes

• During meiosis I, homologous chromosomes line up, but there are millions of combinations that occur during the line up

Fig. 9-21

2.) Crossing Over

• When homologous chromosomes are lined up and waiting to separate in Meiosis I, pieces of chromosomes can be exchanged between homologues.

3.) Fusion of gametes

• Any given sperm can fertilize any given egg• Every human can theoretically produce 8 million

different gametes• 8 million different eggs AND 8 million different sperm

= 64 TRILLION different possible zygotes! That’s 64 trillion genetically different children!

• Add crossing over and shuffling of homologous chromosomes, and you can begin to see why there are so many DIFFERENT looking people on earth!

Inheritance

• How do humans inherit a wide variety of traits like hair color, eye color, skin tone, height, etc?

• Answer? Mendelian Genetics• Mendel did genetic experiments with pea

plants, which are easy to control and breed.

Mendel’s Basic Rules*

• Mendel found out some very basic rules about genetics and inheritance that are applicable to humans: – Each trait is determined by PAIRS of genes. Each

organism has TWO alleles for each gene, one from mom and one from dad. These alleles are located on homologous chromosomes.

– When two DIFFERENT alleles are present in an organism, one of them (the DOMINANT gene) may mask the expression of the other (the RECESSIVE gene)

Traits are determined by genes on homologous chromosomes

Example of Dominant/Recessive*

• Purple is the dominant allele, white is recessive.

• This means that as long as there is ONE purple gene, the flower will be purple (even if the allele on the other homologous chromosome is white.)

• There must be TWO white alleles in order for the flower to be white.

Mendel’s Basic Rules*

• An organism can have TWO copies of the SAME allele (Ex: 2 genes for white flower color). These organisms are termed “homozygous” for that allele.

• Or an organism can have DIFFERENT alleles for a trait (Ex: one gene for purple color and one gene for white color). These organisms are termed “heterozygous” for that allele.

Heterozygous vs Homozygous

What about traits that are the result of more than one gene?*

• *Important: Mendelian genetics explain the pattern of inheritance in traits that are the result of a SINGLE gene.

• Traits that are the result of multiple genes are explained by POLYGENIC INHERITANCE (height, weight, skin tone, eye color, IQ). For these traits, there is a large range of expression and MULTIPLE GENES CONTRIBUTE to the expression of these traits.

• Traits are also influenced by environment, nutrition, and parental influence

Example of polygenic trait: Eye Color

• Two genes on Chromosome 15, one on Chromosome 19

• BEY 1 Gene (15): 2 allele possibilities (brown/blue) brown is dominant

• BEY 2 Gene – CENTRAL BROWN GENE – (15): 2 allele possibilities (on/off)

• GEY Gene (19): 2 allele possibilities (green/blue) green is dominant but recessive to ALL BROWN alleles

Draw pic of eye color combos

Extensions of Mendelian Genetics*

• Genotype: an organism’s DNA makeup• Phenotype: how an organism LOOKS• Genotype affects phenotype• Nondisjunction: failure of chromosome pairs to separate

during Meiosis (results in trisomies)• Codominance: Neither alleles is dominant - BOTH ALLELES

ARE EXPRESSED• Incomplete Dominance: Heterozygotes have an

INTERMEDIATE phenotype between the homozygotes.

Codominance

• Ex: Blood Type• There is one gene for blood type, but 3 allele

possiblities: A, B, or O. • This gene codes for a protein on the surface of

blood cells.• Mom can donate A, B, or O• Dad can donate A, B, or O• BOTH alleles will be expressed

Possibilities for Blood Type

Blood Type

Incomplete Dominance

• Ex: Snapdragon• Gene for flower color• 2 allele possibilities: Red and White • 2 Red alleles: Red Flower• 2 White alleles: White Flower• One Red and One White allele: Pink flower• Neither allele is dominant, the heterozygote

(phenotypically) is an intermediate between each allele.

Snapdragon Color