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Chapter 10 (Part 1)
DNA, Genes, and Chromosomes
Section 1: Molecule of Heredity (History)
Genetic Material Transforms Cells
Griffith’s Experiments
1.
2.
3.
4.
S bacteria injected into mice caused death
R bacteria injected into mice had no effect
S bacteria were killed by heating, then injected into
mice…had no effect
Grew live R bacteria and mixed it with S bacteria, then
injected into mice…caused death.
**Reasoned that some how a transforming material passed
from heat-killed S bacteria to living R bacteria changing R
bacteria to S bacteria.
**Transforming material is genetic material.
1944 Oswald Avery
-Discovered only DNA from strain S was necessary to
transform strain R bacteria to the S strain.
-Support the theory that DNA is the molecule of heredity.
DNA or Protein, which is “Genetic Material”?
1952 Chase and Hershey
-Experimented with bacteriophages or phages (viruses that
infect bacteria only)
Phage
-2 components
1-DNA
2-protein
-when phages infect bacteria, attach to bacterium’s
surface and inject material into the bacterium
-rest of phage stays outside bacterium
-injected material controls the metabolism and
characteristics of bacterial cells like genes
-injected substance must be the genetic material
-to find out mixed phages containing radioactive DNA
with bacterial cells
-also mixed phages containing radioactive protein with
bacterial cells
-after material was injected bacteria began producing
new phage viruses
-only radioactive DNA entered the bacteria
Section 2: DNA Structure and Replication
Nucleotides and Bases
What is the structure of DNA?
**Structure is related to function
-Twisted ladder made of nucleotides
DNA nucleotide
3 components (P.A. Levene, 1920’s)
1-five carbon sugar (deoxyribose)
2-phosphate group
3-one of 4 nitrogen bases
Nitrogen Bases
A-adenine
G-guanine
C-cytosine
T-thymine
Purines-adenine and guanine
Pyramidines-cytosine and thymine
(Erwin) Chargaff
-discovered always same amount of adenine and thymine
-also always same amount of guanine and cytosine
Double Helix
(Maurice) Wilkins and (Rosiland) Franklin
-photographed DNA using X rays
-image showed wide tightly coiled molecule with spiral shape
Double helix: DNA molecule is shaped like a twisted ladder and
formed by 2 strands of nucleotides
Watson and Crick
-sugar and phosphate bind to form backbone of DNA
(back/legs of the ladder)
-nucleotides bind together with weak chemical bonds (rungs of
the ladder)
**Each base pair is formed from a purine and a pyramidine
-adenine always pairs with thymine
-guanine always pairs with cytosine
DNA Replication
Replication: the process by which DNA is copied
-occurs prior to cell division during interphase
3 steps of replication
1-DNA unzips
-enzymes split apart base pairs and unwind the DNA
double helix
2-Bases pair up
-free nucleotides in the cell find their complementary
bases along the new strands with the help of DNA
polymerase (an enzyme)
3-Backbone bonds
-the sugar-phosphate backbone is assembled to complete
the DNA strand
**2 new double helixes are formed
Section 3: Linked Genes
Linkage
A single chromosome contains many different genes that control
many different traits
DNA
nucleotides
section of DNA (gene)
chromosome
City
people
one building
many buildings (1 street)
Theory of Heredity: specific genes controlling specific traits are located
on specific Chromosomes
Bateson and Punnett’s Experiment
P
F1
F2
PPLL x ppll
PpLl
not 9:3:3:1…greater than expected number has phenotype of
P Generation
**Determined that traits were some how linked and did not sort
independently
Linked genes: those that are located on the same gene
-do not sort independently
Recombination
-new combination of traits was the result of a change in the position
of alleles
Recombination: the process where there are new combinations of alleles
Recombinant: the offspring that occur
Tetrads: set of 4 chromosomes
Crossing over: refers to the recombining of alleles that occur when
neighboring segments of tetrads break off when they
meet and exchange genetic material
Mapping: scientists use recombination data to determine location of
certain genes
Gene Mapping
-geneticists work with two traits (from two genes at a time)
-collect statistics on the inheritance of two traits
-inherited independently=not on same chromosome
-not inherited independently=traits are linked
Section 4: Sex Linkage
Sex Chromosomes
Sex Chromosome: determine whether the offspring are male or
female
Autosomes: non-sex chromosomes
Females: XX – all eggs have a single X chromosome
Males: XY – 1/2 the sperm have an X and 1/2 have a Y chromosome
Sex-Linked Traits
Sex-linked genes: genes found only in the X chromosome are
linked…genes found only in the Y chromosome are Y-linked
P
Red-eyed female x White-eyed male
F1
Males and females all red-eyed
F2
1/2 red-eyed females
1/4 red-eyed males
1/4 white-eyed males
Sex-linked traits in humans:
Red-green color blindness caused by
X-linked recessive allele (Xc)
(allele for normal color vision XC)
color blind male XcY
color blind female XcXc
Hemophilia caused by X-linked allele
Males get X-linked traits from their mothers
Females get X-linked traits from both parents
Sex-limited and sex-influenced traits
Sex-limited traits: only expressed in the presence of sex hormones
and are only observed in one sex or the other
-controlled by genes in autosomes
-in order for sex-limited trait to be expressed the appropriate
sex hormone must be present
-most not expressed in children
-beard growth in men
-milk production in women
Sex-influenced traits: expressed in both sexes
-allele for baldness
-in presence of male sex hormones is dominant
-in presence of female sex hormones is recessive
Section 5: The Human Gene Map
Genomes
Karyotype: a photograph of all of an organism’s chromosomes
-freeze cells at metaphse
-isolate and stain chromosomes
-homologous pairs are grouped
Genome: the base sequence of all the DNA in an organism
-Human genome = 3 billion bases
Human Genome Project
-sequencing the DNA in the human body
-genes already identified (cir. 1998): cystic fibrosis, Duchenne
muscular dystrophy, Huntington’s disease
Changes in the Genome
Nondisjunction: failure of chromosomes to separate during cell division
-“not separating”
-nondisjunction during mitosis cell dies
-nondisjunction during meiosis in anaphase I or II causes
chromosomes to stay together. This can produce an
abnormal sex cell in meiosis which, if fertilized, will produce
an offspring with too many (or too few) chromosomes
"Nondisjunction disorder"
Monosomy: the zygote has only one copy of a particular chromosome
Trisomy: the zygote has three copies of the chromosome
Down’s Syndrome: Trisomy 21
Trisomy of sex cells: XXX or XXY
Monosomy of sex cells: XO
Polyploidy: nondisjunction occurs in all chromosome pairs
-organism has more than 2 entire sets of chromosomes
-animals = death
-plants = robust plants
Chapter 10 (Part 2) & 11:
Protein Synthesis & Gene Control
Section 1: From Genotype to Phenotype
What do you already know about proteins?
How do proteins relate to DNA, genes, and chromosomes?
Remember: Who we are in terms of unique traits, abilities, health (both
positive and negative) are directly related to proteins!
Gene Expression
Protein Synthesis: The process by which an organism’s genotype (or
genetic makeup) is translated into its phenotype (or
traits).
-Genes code for the sequence of amino acids that make up proteins
-Genes are made of DNA
-The sequence of DNA bases in a gene determines the composition
of proteins
-Some genes code for proteins that regulate expression of other
genes
-A gene is “expressed” when the protein that it codes for is
synthesized
RNA: Ribonucleic acid
-Single-stranded nucleic acid
-Works with DNA to make proteins
-Three (3) types of RNA
-Messenger RNA (mRNA)
-Transfer RNA (tRNA)
-Ribosomal RNA (rRNA)
transcription
DNA --------------------------> RNA
translation
--------------------------> Protein
Two stages of protein synthesis
1. Transcription: Genetic information from DNA copied to a strand
of mRNA
-RNA polymerase and other enzymes “unzip” DNA
-RNA polymerase then binds unattached RNA bases to their
complementary bases on the DNA stand
2. Translation: The code or “language” located within the nucleic
acids (bases) is changed into the “language” of
proteins (amino acids)
Building RNA
DNA and RNA Structural Differences:
DNA
1. Double-Stranded
2. Deoxyribose sugar group
3. Base pairs: C - G, A -T
G = Guanine
C = Cytosine
A = Adenine
T = Thymine
RNA
Single-Stranded
Ribose sugar group
Base pairs: C - G, A - U
G = Guanine
C = Cytosine
A = Adenine
U = Uracil
**Prokaryotic cells: mRNA goes directly to ribosomes for translation
**Eukaryotic cells: RNA must be spliced, shipped to cytoplasm, then
translated by ribosomes
-Eukaryotic DNA contains introns/exons
-Introns: The regions of DNA or RNA that do not code for proteins
-Exons: The regions of DNA or RNA that code for proteins
-Splicing: The removal of introns and joining of remaining exons in
mRNA
Building Proteins
There are 3 steps to protein synthesis:
1. Initiation
2. Elongation
3. Termination
In the cytoplasm:
-mRNA attaches to ribosome (either free floating or attached to the ER)
-Ribosome/mRNA complex ready to synthesize proteins (Initiation)
-tRNA functions in transporting amino acids to the ribosomes
-Each additional amino acid links with the last forming a chain
-The lengthening of the amino acid chain is called Elongation
-When the ribosome reads a stop signal, the ribosome is released
and a complete protein is formed (Termination)
Amino acid specification:
-Codon: A three-base section of mRNA that carries a code for a
specific amino acid
-Example: AUG codes for the amino acid Methionine
-Anticodon: A sequence of three bases found on tRNA that
complements a specific mRNA codon
-Codons/Anticodons translation mechanism ensures the order of
amino acids specified by the original DNA template!
-Several codons serve a different purpose: signal ribosomes to
start/stop translation
-The codes for amino acids (as well as start/stop codons) identical in
all living organisms!
-How many possible combinations of codons/anticodons are there?
Answer: 64
-How many different amino acids (aa) are there?
Answer: 20 aa (1 start/3 stop signals)
DNA:
T A C A T G C C G A C T
mRNA:
A U G U A C G G C U G A
tRNA:
U A C A U G C C G A G U
Amino Acid carried by tRNA: Methionine (start), Tyrosine, Glycine, Stop
Section 2: Protein, Phenotype, and Control
Proteins and Cell Functions
-You are made of over 30,000 different proteins!
-Any alteration has the ability to change a protein, and thus change you!
-Genes can be “turned on” and “turned off”
Gene activation: A genes product or protein is in the process of being
synthesized by the cell
Control in Prokaryotes
Example of bacterial control of gene expression: lac operon
-E. Coli needs 3 enzymes to digest the sugar lactose
-Genes for these enzymes are grouped together on the E. Coli
chromosome
-Enzymes only needed when lactose is present
-Repressor: A protein that binds to DNA, turning of a gene (in this
case, the genes that code for the digestive enzymes)
-Promoter: A section of DNA that serves as the binding site for the
enzyme RNA polymerase
- Regulator gene: codes for the repressor
- Operator gene: attachment for repressor protein
- Structural genes: code for different proteins the cell needs to make
Here is how gene expression is regulated in E. Coli:
Genes Off:
-A regulatory gene codes for the production of a repressor
-The subsequent protein binds to DNA
-Binding of repressor prevents RNA polymerase from binding to
promoter
-Protein synthesis of the digestive enzymes can not occur!
Inactivation of Repressor:
-Level of lactose increases in the cell
-Lactose binds to the repressor, changing its shape
-Altering the shape of a repressor prevents its binding to DNA
-RNA polymerase is free to bind to the promoter
Genes On:
-RNA polymerase moves along the DNA producing mRNA
-mRNA is translated producing the digestive enzyme lactase
-The enzyme digests all of the lactose present
-The repressors shape changes back to its original form
-The repressor once again binds to and blocks the promoter
Control in Eukaryotes
-Gene control more complex in humans
-So many specialized cells & tissues require complex systems of gene control
Examples: Selective gene expression
Complex regulatory systems
Control of RNA splicing
Section 3: Changes in Chromosomes (Proteins and Mutations)
Possible functions of proteins:
-Carry out functions w/in the cell
-Exported from cell for other purposes
-Activators or repressors (turn genes on/off)
Mutation: A random change in the sequence of nucleotides in DNA
-may have little/no effect, harmful, or (rarely) beneficial
-happens randomly every few thousand cell divisions
-can occur in somatic cells or in germ cells
Two types: chromosomal mutations and gene mutations
Chromosomal Mutations
-Chromosomal mutations are changes in the structure of a chromosome
-Four types: deletion, duplication, translocation, and inversion
1. Deletion: Chromosome breaks and a piece of chromosome is lost
(usually lethal)
2. Duplication: Part of a part of a chromosome breaks off and is
incorporated into its homologous chromosome
3. Translocation: A part of a chromosome breaks off and attaches to a
different, non-homologous chromosome
4. Inversion: When part of a chromosome breaks off, turns around
(inverts), and reattaches in the reverse order
Gene Mutations
-Gene mutations are errors that occur w/in individual genes in a chromosome
-Can involve single nucleotides or larger sections of DNA
-Three types: Frameshift mutations, point mutations, and jumping genes
1. Frameshift: The deletion or addition of nucleotides resulting in the
disruption of codons
-can alter the sequence of bases (or reading frame) of the genetic
message
2. Point: A change that occurs in only one nucleotide; the substitution of
one base
-usually less disruptive (~30% have no affect at all; results in one aa
for another)
-sickle-cell anemia caused by a point mutation that results in an aa
substitution
-Rare: point mutation causes a stop signal instead of aa substitution
(drastic)
-Example: DNA:
TAC CAG TCA ATT
mRNA: AUG GUC AGU UAA
Protein: Met
Val
Ser Stop
Frameshift Mutation: DNA: TAC CAT CAA TT
mRNA: AUG GUA GUU AA
Protein: Met
Val
Phen
Point Mutation:
DNA:
TAC CAG TCC ATT
mRNA:
AUG GUC AGG UAA
Protein:
Met
Val
Arg Stop
3. Jumping Genes: Occurs when large stretches of DNA are inserted into
a gene (Barbara McClintock/maize)
Section 4: Genes and Cancer
Mutations and Control
-When mutations change genes that control cell growth and specialization,
cancer may result!
- Sarcomas: grow in muscle or bone
Lymphomas: solid tumors that grow in tissues that form blood cells
Leukemia: abnormal growth of white blood cells
Tumors: abnormal mass of cells that results from uncontrolled cell
division.
benign: non-spreading, contained
malignant: spreads to other locations (metastatic)
-3 Causes of Cancer Formation: Inheritance, Environmental Factors, or the
Combination
-All have one common feature: The genes that control new cells do not
turn off
Oncogene: A gene that causes a cell to become cancerous (ex: MDM2)
Three ways a gene can become oncogenic (and its effect):
1. Mutation of a growth-factor gene (creates super growth factor)
2. Error in DNA replication (normal growth factor but multiple copies)
3. Translocation (stronger promoter creates more normal growth
factor)
Other genes that cause cancer:
Tumor Suppressor Genes: Genes that prevent uncontrolled cell growth
(ex: p53 and Rb)
-mutations in tumor suppressor genes (also called anti-oncogenes)
are major factors in many forms of cancer!
Causes of Gene Mutations
-Environmental factors play a major factor
-People with predispositions have higher chances of developing certain
cancers
Mutagens: A factor in the environment that can cause mutations in DNA
(ex: radiation)
-does not always cause cancer!
Carcinogen: An agent that causes or tends to cause cancer (ex: cigarette
tar, some viruses [CMV]...)
Ames test: A test devised by scientists to measure the carcinogenic levels
of chemicals
Frontiers in Biology/Prevention
-Not all bad news!
-With increased research, science has discovered the amazing ability of the
body to fight cancer
-Scientists has devised new and better techniques to fight cancer
(viruses/gene therapy, chemotherapy, radiation, and early detection)
-Cancer screenings important in prevention but depend upon: age, sex,
and family history
-Avoid smoking! 1/3 of all cases of cancer in U.S. linked to cigarette
smoking!
-Other ways to prevents cancers: Healthy diet and limiting sun exposure