Larry M. Frolich, Ph.D. Biology Department, Yavapai College GENETICS

Larry M. Frolich, Ph.D.Biology Department, Yavapai College

GENETICS


GENETICS• Cells divide and pass on

instructions coded in DNA of chromosomes

• Each chromosome is a huge DNA molecule with coded information– DNA replicates to pass on information– DNA is transcribed to make proteins

that run cell metabolism

• Cancer—example of what happens when genetic control goes awry

• Normal inheritance and meiosis


GENETICS

• Cells divide and pass on instructions coded in DNA of chromosomes

• Each chromosome is a huge DNA molecule with coded information

– DNA replicates to pass on information– DNA is transcribed to make proteins that run cell

metabolism




DNA and chromosomes• Long DNA molecules (millions

of base pairs long) in nucleus are called chromosomes

• Each chromosome is organized and packaged or wrapped up with proteins giving it a certain shape

• In humans, 23 pairs of chromosomes– 1 of each pair from mother– 1 of each pair from father

• Total view of all 23 pairs is called karyotype


Mitosis—cell division

• Why do cells divide?– Growth—so tissues/structures can become

larger– Replacement—many tissues are constantly

being replaced because they get worn out or used up. E.g. blood, skin, lining of gut, sperm

– Repair—when tissues get damaged due to injury


Mitosis—what happens (overview)• DNA/chrosomes replicate

(make exact copies• Copies line up at center

of cell• Copies pulled to opposite

ends of cells by centromeres/spindles

• Cell membrane pinches off and splits cell into two


Mitosis—details/stages

1. Prophase

2. Metaphase

3. Anaphase

4. Telophase


1. Mitosis: Prophase

• Chromosomes condense and become visible

• Nuclear envelope fragments

• Nucleolus disappears

• Centrosomes move to opposite poles

• Spindle fibers appear and attach to the centromere


2. Mitosis: Metaphase

• Chromosomes line up at the middle of the cell (equator)

• Fully formed spindle


3. Mitosis: Anaphase

• Sister chromatids separate at the centromeres and move towards the poles


4. Mitosis:Telophase and cytokinesis

• Chromosomes arrive at the poles

• Chromosomes become indistinct chromatin again

• Nucleoli reappear• Spindle disappears• Nuclear envelope

reassembles• Two daughter cells are

formed by a ring of actin filaments (cleavage furrow)


Mitosis—constant, fast, keeps body functioning

• Remember, mitosis produces two identical daughter cells

• Mitosis is constantly happening in your body to allow for growth, replacement and repair

• While you read this slide, millions of new cells were produced by mitosis in the tissues of your body!

• Don’t forget cellular scale and intelligence—it’s a whole planet happening at the sub-microscopic level


GENETICS• Cells divide and pass on instructions coded in DNA of

chromosomes

• Each chromosome is a huge DNA molecule with coded information– DNA replicates to pass on

information– DNA is transcribed to make

proteins that run cell metabolism• Cancer—example of what happens when genetic

control goes awry



Chrosomes

• REVIEW: Each chromosome is a single DNA molecule wrapped up within a special group of proteins giving it a particular shape


DNA is structured to replicate

• DNA is “double helix”—two complementary strands wound in a spiral

• Strands separate and DNA replicates by filling in other half of each separated strand

• Famous Watson-Crick model (Nobel prize)


DNA replicates to pass on information (to daughter cells in mitosis)


DNA is transcribed to make proteins that run cell metabolism

• DNA is transcribed to mRNA

• mRNA is translated to amino acid sequence

• Amino acid sequence folds up into protein

• Proteins catalyze reactions of cell metabolism

• This process is called “gene expression”—the information in one region of the DNA—a “gene”—is being expressed so that the cell’s metabolism can function


2 steps of gene expression

1. Transcription – DNA is read to make a mRNA in the nucleus of our cells

2. Translation – Reading the mRNA to make a protein in the cytoplasm


Transcription

• Happens in nucleus• DNA double helix

“opens up”• mRNA transcript is

made from DNA template


Translation• Happens outside

nucleus• Ribosomes (special

RNA particles or organelles) do the translation

• They glom onto mRNA and line up amino acids according to mRNA sequence (see next slide for “code”


RNA-protein translation code

• Every three RNA bases codes for one amino acid

• This code is very evolutionary conservative—works almost the same in all forms of life


Overview of transcription and translation

Details in web link video animations

REMEMBER: A particular region of DNA that has the code to make a particular protein is called a “gene.”


How does cell decide when to activate which genes to produce what proteins?

• DNA must be unpackaged and uncoiled in order to be transcribed to mRNA

• Lampbrush chromosome shows loops of DNA that are being transcribed

• What determines which regions or genes are going to be transcribed and translated?

• This is called regulation of gene expression


Regulation of gene expression• Gene expression is regulated—not all genes are

constantly active and having their protein produced• The regulation or feedback on gene expression is how the

cell’s metabolism is controlled. • This regulation can happen in different ways:

1. Transcriptional control (in nucleus):• e.g. chromatin density and transcription factors

2. Posttranscriptional control (nucleus)• e.g. mRNA processing

3. Translational control (cytoplasm)• e.g. Differential ability of mRNA to bind ribosomes

4. Posttranslational control (cytoplasm)• e.g. changes to the protein to make it functional

• When regulation of gene expression goes wrong—cancer!


DNA technology

• Recombinant DNA

• DNA sequencing and Human Genome Project

• “Genetic Engineering”

NOTE: This is probably going to be the century for biological technology. What we’ve done with smart silicon systems will soon seem like nothing compared to what we will do with smart carbon/life-based systems. The technologies to understand, build, manipulate and control DNA, protein and cellular systems have been growing for the last fifty years and will undoubtedly keep doing so. Please view the web links and do the ethical issue essay for this part of the course. I think you’ll find the DNA technologies and our ability to manipulate cell metabolism fascinating!



chromosomes



metabolism




Characteristics of cancer cells1. Lack differentiation and do not contribute to body functioning2. Have abnormal nuclei that are enlarged and may have an

abnormal number of chromosomes 3. Unlimited ability to divide

• one way is through turning on the telomerase gene that allows telomeres on chromosomes to continually be built thus allowing a cell to divide over and over again

4. Form tumors • Benign tumors are usually encapsulated and do not invade adjacent

tissue while a cancerous tumor usually is not encapsulated and eventually invades surrounding tissue

5. Can divide without growth factors6. Become abnormal gradually through a multistage process7. Undergo angiogenesis and metastasis


The 3 phases in the development of cancer cells

• Initiation – a single cell undergoes a mutation that causes it to divide repeatedly

• Promotion – a tumor develops and cells within the tumor mutate

• Progression – a cell mutates in such a way that allows it to invade surrounding tissue


The genetic basis for cancer

• Proto-oncogenes – products promote the cell cycle and prevent cell death (apoptosis)

• Tumor-suppressor genes – products inhibit the cell cycle and promote apoptosis

• Mutations in the genes above can cause cancer, in fact proto-oncogenes that have mutated are cancer-causing genes called oncogenes


Comparing these genes in normal and cancer cells


Types of cancer

• Oncology – study of cancer• Carcinomas: cancers of the epithelial tissue• Adenocarcinomas: cancers of glandular

epithelial cells• Sarcomas: cancers of muscle and connective

tissues• Leukemias: cancers of the blood• Lymphoma: cancers of lymphatic tissues

CANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?


Causes of cancer

• Genetics

• Environmental carcinogens– Radiation– Environmental carcinogens (tobacco smoke

and pollutants)– Viruses



Genetic causes of cancer

• Examples of genes associated with cancer:– BRCA1 and BRCA2 – tumor-suppressor genes that

are associated with breast cancer– RB – a tumor-suppressor gene that is associated

with an eye tumor– RET – proto-oncogene that is associated with thyroid

cancer

• Mutations of these genes predispose individuals to certain cancers but it takes at least one more acquired mutation during their lifetime to develop cancer



Environmental causes of cancer• Radiation:

– Environmental factors such as UV light (in sunlight or tanning lights) and x-rays can cause mutation in DNA

• Organic chemicals:– Tobacco smoke: increases cancer of lungs, mouth, larynx and

others– Pollutants: substances such as metals, dust, chemicals and

pesticides increase the risk of cancer

• Viruses:– Hepatitis B & C: virus that can cause liver cancer– Epstein-Barr virus: can cause Burkitt’s lymphoma– Human papillomavirus: can cause cervical cancer



Seven warning signs of cancer

• Change in bowel or bladder habits

• A sore that does not heal

• Unusual bleeding or discharge

• Thickening or lump in breast or elsewhere

• Indigestion or difficulty in swallowing

• Obvious change in wart or mole

• Nagging cough or hoarseness



Some routine screening tests for cancer

• Self-examination – monthly exams of breasts and testicles starting at age 20

• Colonoscopy – every 5 years starting at age 50

• Mammogram – yearly after age 40

• Pap smear – should begin these 3 years after vaginal intercourse or no later than age 21



Health Focus: Self examsCANCER QUICK COURSE—WHAT CAN YOU DO TO PREVENT/TREAT?


Detecting skin cancer

• A – asymmetry• B – border is

irregular• C – color varies from

one area to another• D – diameter is

larger than 6mm



Other ways to detect cancer• Tumor marker tests – blood tests for tumor

antigens/antibodies– CEA (carcinoembryonic antigen) antigen can be detected in

someone with colon cancer– PSA (prostate-specific antigen) test for prostate cancer

• Genetic tests – tests for mutations in proto-oncogenes and tumor-suppressor genes– RET gene (thyroid cancer)– P16 gene (associated with melanoma)– BRCA1 (breast cancer)

• A diagnosis of cancer can be confirmed by performing a biopsy



Standard cancer treatments• Surgery – removal of small cancers

• Radiation therapy – localized therapy that causes chromosomal breakage and disrupts the cell cycle

• Chemotherapy – drugs that treat the whole body that kills cells by damaging their DNA or interfering with DNA synthesis

• Bone marrow transplants – transplant bone marrow from one individual to another



Newer cancer therapies• Immunotherapy – inject immune cells that are genetically

engineered to bear the tumor’s antigens

• Passive immunotherapy – antibodies that are linked to radioactive isotopes or chemotherapeutic drugs are injected into the body

• p53 gene therapy – a retrovirus in clinical trial that is injected into the body where it will infect and kill only tumor cells (cells that lack p53 = tumor cells)

• Angiogenesis inhibition - Angiostatin and endostatin are drugs in clinical trials that appear to inhibit angiogenesis



Bioethical focus: Control of tobacco• Food for thought:

• Smoking diminishes the health of the smoker and damages nearly every major organ

• Within minutes of smoking, a smoker’s body begins to heal• Smoking low-tar or low-nicotine is no different than smoking any

other cigarette• The tobacco industry targets young people (9 out of 10 smokers

start before age 18)• It is the single most preventable cause of death and disease in

the US

• Give your thoughts:• Who should pay for the medical bills associated with smoking?• Should the government prevent the sale of tobacco or leave it up

to the individual?




chromosomes



metabolism




How are genetic traits combined and passed on from parent to offspring

• Meiosis produces gametes or sex cells (eggs and sperm) with just one member of each chromosome pair

• Fertilization results in union of female gamete (egg) with male gamete (sperm)

• Subsequent embryonic, fetal and embryonic development by mitosis and differentiation of cell types produces new individual


Overview of meiosis

• Two nuclear divisions occur to make 4 haploid cells (cells with just one member of each chromosome pair)

• Meiosis results in gametes (egg and sperm)

• Has 8 phases (4 in each meiosis I & II)

18.3 Meiosis


Alleles• A particular gene, or protein-coding region of

DNA along a chromosome might have a few different variations, called alleles

• The combination of alleles, at a particular gene, or chromosome region, that you get from your mother and father determine your hereditary traits

• Please see the Dragon Genetics lab to understand this (in online lab links for this section)


• After meiosis, male and female gametes (sperm and egg) unite to form a new cell—a zygote—that has the full set of 23 pairs of chromosomes.

Fertilization


Embryonic development—mitosis produces tissues/structures of adult



Some adult features are coded for genetically in alleles or gene varieties of sperm and egg

Be sure to see sickle cell anemia example in Web Links for this section of the course


Inheritance and Natural Selection• Some combinations of alleles, produced during meiosis

and fertilization might be more advantageous• This is what leads to natural selection. Individuals with

more advantageous traits will survive to reproduce and pass on those traits.

• Darwin realized that slow changes in inherited traits, due to natural selection produced the great evolutinoary history of life.

• Before his synthesis of all the evidence, no one could make sense of living systems. Now, “Nothing in Biology Makes Sense Except in the Light of Evolution”

• --Theodosius DobzhanskyPlease do the Coyote Lab to see how meiosis, fertilization, inheritance and natural selection all work together to produce the gradual change in biological organisms that we call evolution. You can download this lab from the Online Lab links for this section of the course.



GENETICS• Cells divide and pass on

instructions coded in DNA of chromosomes






GENETICS (review)

• Cells divide and pass on instructions coded in DNA of chromosomes






DNA and chromosomes• Long DNA molecules (millions

of base pairs long) in nucleus are called chromosomes

• Each chromosome is organized and packaged or wrapped up with proteins giving it a certain shape

• In humans, 23 pairs of chromosomes– 1 of each pair from mother– 1 of each pair from father

• Total view of all 23 pairs is called karyotype


Mitosis—what happens (overview)• DNA/chrosomes replicate

(make exact copies• Copies line up at center

of cell• Copies pulled to opposite

ends of cells by centromeres/spindles

• Cell membrane pinches off and splits cell into two


Mitosis—constant, fast, keeps body functioning

• Remember, mitosis produces two identical daughter cells

• Mitosis is constantly happening in your body to allow for growth, replacement and repair

• While you read this slide, millions of new cells were produced by mitosis in the tissues of your body!

• Don’t forget cellular scale and intelligence—it’s a whole planet happening at the sub-microscopic level


DNA is structured to replicate

• DNA is “double helix”—two complementary strands wound in a spiral

• Strands separate and DNA replicates by filling in other half of each separated strand

• Famous Watson-Crick model (Nobel prize)


DNA is transcribed to make proteins that run cell metabolism

• DNA is transcribed to mRNA

• mRNA is translated to amino acid sequence

• Amino acid sequence folds up into protein

• Proteins catalyze reactions of cell metabolism

• This process is called “gene expression”—the information in one region of the DNA—a “gene”—is being expressed so that the cell’s metabolism can function


Overview of transcription and translation

Details in web link video animations

REMEMBER: A particular region of DNA that has the code to make a particular protein is called a “gene.”


Regulation of gene expression• Gene expression is regulated—not all genes are

constantly active and having their protein produced• The regulation or feedback on gene expression is how the

cell’s metabolism is controlled. • This regulation can happen in different ways:

1. Transcriptional control (in nucleus):• e.g. chromatin density and transcription factors

2. Posttranscriptional control (nucleus)• e.g. mRNA processing

3. Translational control (cytoplasm)• e.g. Differential ability of mRNA to bind ribosomes

4. Posttranslational control (cytoplasm)• e.g. changes to the protein to make it functional

• When regulation of gene expression goes wrong—cancer!


How are genetic traits combined and passed on from parent to offspring

• Meiosis produces gametes or sex cells (eggs and sperm) with just one member of each chromosome pair

• Fertilization results in union of female gamete (egg) with male gamete (sperm)

• Subsequent embryonic, fetal and embryonic development by mitosis and differentiation of cell types produces new individual


• After meiosis, male and female gametes (sperm and egg) unite to form a new cell—a zygote—that has the full set of 23 pairs of chromosomes.

Fertilization


Inheritance and Natural Selection• Some combinations of alleles, produced during meiosis

and fertilization might be more advantageous• This is what leads to natural selection. Individuals with

more advantageous traits will survive to reproduce and pass on those traits.

• Darwin realized that slow changes in inherited traits, due to natural selection produced the great evolutinoary history of life.

• Before his synthesis of all the evidence, no one could make sense of living systems. Now, “Nothing in Biology Makes Sense Except in the Light of Evolution”

• --Theodosius DobzhanskyPlease do the Coyote Lab to see how meiosis, fertilization, inheritance and natural selection all work together to produce the gradual change in biological organisms that we call evolution. You can download this lab from the Online Lab links for this section of the course.

Documents

Larry M. Frolich, Ph.D. Biology Department, Yavapai College GENETICS