Domain 4: Information

4.1: DNA, and in some cases RNA, is the primary source of

heritable information. (EK3.A.1)

1. DNA Structure
DNA is the hereditary material in all cells.
This understanding is the result of work done by many scientists over the past 100
years.

Frederick Griffith: Determined the molecular basis of heredity due to experiments

with different strains of bacteria.

Avery, McCarty and McLeod: Determined that DNA was the hereditary molecule in
cellular systems.

Hershey and Chase: Conclusively verified the work of Avery, McCarty, and McLeod.

Erwin Chargaff: Determined that the amount of adenine = the amount of thymine,
and the amount of guanine = the amount of cytosine in any DNA sample.

Watson, Crick, Franklin, and Wilkins: Determined the structure of DNA, and
related the structure to the role of DNA in heredity.

DNA & RNA Structure and function:

DNA and RNA are both nucleic acids made of nucleotide monomers.

1
 Nucleotides are comprised of a 5-carbon sugar, a nitrogenous base, and a
phosphate group.

Nucleotides exist in the cytoplasm as nucleoside tri-phosphates (ex ATP, GTP).

The extra phosphates provide the energy necessary for a nucleotide to be
incorporated in to a nucleic acid.

In DNA, the sugar is deoxyribose. In RNA the sugar is ribose.

The DNA bases are Adenine, Thymine, Guanine and Cytosine. The RNA bases are
Adenine, Uracil, Guanine and Cytosine.

RNA is usually single stranded (nucleotides still H-bond with eachother due to
bending of the RNA molecule), DNA is usually double stranded.

Nucleotides in one strand are covalently bonded between the sugar and phosphate.
Nitrogenous bases hydrogen bond with nitrogenous bases on opposite strands.
Adenine and thymine/uracil form 2 Hydrogen bonds, Guanine and cytosine form
3 hydrogen bonds. A specific purine (2 rings) always H-Bonds with a specific
pyrimidine (1 ring).

One strand of a nucleic acid has a directionality, referred to as 5 and 3, depending

on which carbon of the sugar is exposed at the terminal nucleotide.

The two DNA strands are anti-parallel in orientation.

2
The organization of nucleic acids differs in prokaryotes, eukaryotes, and viruses:
Prokaryotes:
Have one circular chromosome, often with at least one small extra-
chromosomal circular plasmid.

Eukaryotes:
Have many linear chromosomes. Plasmids are rare.

Viruses:
Have a much smaller amount of genetic material than cells. The viral genome can be
DNA or RNA, and single stranded or double stranded.

2. DNA Replication
DNA is the information storage molecule in living systems.
The Central Dogma of molecular biology: Expresses the major flow of information
in biological systems.
DNA molecules are duplicated (replication) to convey information between
generations of cells.

DNA information is transcribed in to RNA and then translated in to proteins in

order to participate in cellular activities.

There are other, non-typical paths for information flow seen in viral systems.

DNA Replication allows for heritability:

3
 DNA is replicated in a semiconservative process. One strand of each molecule
serves as the template for the synthesis of the other strand. Each molecule of
DNA is composed of one newly synthesized strand and one pre-existing strand.

Replication is accomplished through the action of a collection of enzymes that all

function together (the replisome).
Helicase: Opens the DNA helix at the origin sequence for replication.

Topoisomerase: Rotates the DNA strand to reduce torsional stress during replication.

DNA Polymerase: Responsible for incorporating free nucleotides in to a new strand

of DNA. Can only add nucleotides to the 3 end of a molecule. Makes mistakes.

Nucleic acids can only be synthesized in a 5 -> 3 direction, which requires one
new strand to be made continuously, while the other strand must be synthesized
in pieces (discontinuously) called Okazaki fragments.

Ligase: Enzyme that forms covalent bonds between adjacent nucleotides in one
strand of DNA. Needed to join the okazaki fragments together.

3. Protein Synthesis
Transcription converts DNA sequence information in to RNA sequence
Information:
RNA polymerase: Enzyme that is responsible for making a strand of RNA (in the
5 to 3 direction) from a sequence of DNA.

4
 RNA plays several roles in the expression of genetic information:
mRNA: RNA sequence of a DNA segment that specifies a polypeptides amino
acid sequence.
tRNA: Molecules that bring specific amino acids to the ribosome, as dictated by
the mRNA sequence.
rRNA: Structural components of ribosome subunits.
Regulatory RNA: Control gene expression by blocking transcription (RNAi).

Translation converts mRNA sequence information in to polypeptide sequences:

Translation occurs at the ribosome.

The genetic code is interpreted as a series of 3-nucleotide codons (three adjacent

nucleotides). There are 64 possible codons, which code for all 20 amino acids,
along with a START codon and 3 STOP codons.

The Genetic code is redundant, unambiguous, and punctuated.

The mRNA interacts with the ribosome to begin translation at the START codon
(AUG) closest to the 5 end of the mRNA.

Following initiation, subsequent amino acids are brought to the ribosome as

specified by subsequent, adjacent codons. Each amino acid is transferred to a
growing polypeptide chain. This is referred to as elongation

5
 This process continues until the first STOP codon is reached, which triggers
termination; the release of the polypeptide from the ribosome, and the
disassembly of the ribosome.

4. Genetic Information Processing & Expression

There are differences in gene processing among viruses, prokaryotes, and eukaryotes.

Viral gene processing:

Some viruses (retroviruses) utilize an enzyme called reverse transcriptase to
convert an RNA genome in to a DNA sequence. This DNA sequence then
integrates in to the host cells genome to allow for continuing expression of viral
components.

Prokaryotic gene processing:

The lack of a nucleus allows prokaryotes to directly couple transcription and
translation. Ribosomes can begin translating an mRNA transcript before RNA
polymerase finishes transcribing it from the DNA.

Eukaryotic gene processing:

Eukaryotes extensively process mRNA transcripts following their production.
There are three major post-transcriptional modifications:
Addition of a poly-A tail to the 3 end of the transcript: Aids in transport of the
mRNA from the nucleus and increases the longevity of the transcript.

Addition of a GTP cap to the 5 end of the transcript: similar in function to the poly
A tail.

6
Removal of introns, and splicing of exons: Introns are interspersed sequences of
nucleotides that do not code for functional parts of a polypeptide. They must be
removed prior to translation if a cell is going to make a functional protein. The
remaining, functional segments (the exons) are spliced together to form the
mature mRNA transcript.

Gene expression contributes to phenotypes through the control of protein activity.

Example: enzymes. Enzymes are proteins, and the reactions that they control will
only occur if those enzymes are present.

Example: Fungal auxotrophs: Mutant strains of fungi with defective copies of

enzymes that are involved in metabolic pathways. These strains will only grow if
they are provided with intermediary nutrients that enter a metabolic pathway
after the action of the defective enzyme.

Example: Albinos: The presence or absence of the normal pigments in an organism

are due to the presence or absence of particular enzymes responsible for pigment
production.

5. Genetic Engineering- Techniques

Genetic Engineering allows for direct manipulation of genetic material.

This differs from selective breeding because it allows for more targeted control of
specific genes.

7
Genetic Engineering Techniques
Electrophoresis: separation of DNA molecules based on their size. Utilizes an
electrical field and a gel matrix (typically agarose). Smaller DNA molecules
migrate through the gel faster than larger molecules. Used to isolate specific genes
from within larger samples of DNA, or to visualize differences in DNA sequences
among a collection of sequences.
Transformation: The direct introduction of DNA sequences in to prokaryotic cells.
The DNA sequences are delivered on plasmid vectors which allow for their
replication and expression of any genes on them by the prokaryotic cell. Used to
engineer prokaryotic cells to produce useful proteins (ex. Human growth
hormone). The eukaryotic version of transformation is called transfection.
Similar purpose, different methodologies.
Restriction Enzyme Analysis: Restriction enzymes cut DNA at specific sequences,
producing restriction fragments. This enables the isolation of different segments
of DNA, for introduction in to plasmids, sequencing, or a variety of other studies.
Regions of the human genome associated with identity and diseases will produce
different length restriction fragments depending on the sequence of DNA present.
Analysis of these Restriction Fragment Length Polymorphisms allows for
establishing identity and genetic testing for different diseases.
Polymerase Chain Reaction: In vitro DNA replication, using a target sequence of
DNA, small primers to bracket the target sequence, a heat-resistant polymerase
originally isolated from a thermophillic bacterium (Thermis aquaticus), and a
thermal cycler, which oscillates between three different temperatures very rapidly.
Through PCR, billions of copies of a DNA sequence can be created in a test tube
over the span of a few hours.

8
6. Genetic Engineering- Applications
Many products can be created using genetic engineering:
Genetically modified foods: genes for desirable characteristics can be inserted in to
the genome of food crops (ex. golden rice)
Transgenic animals: genes for desirable characteristics can be inserted in to livestock
and other animals (ex. Fluorescent fish)
Pharmaceuticals: genes for therapeutic proteins can be inserted in to bacteria to
produce large quantities of those proteins (ex. Insulin).
Cloned animals: Organisms that do not naturally reproduce asexually can be made to
through genome manipulation in the laboratory.

There are many ethical considerations associated with genetic engineering:

Ethical considerations relate to:
Questions of ownership
Questions of consent
Questions of the definition of life, and what should be legally permissible.

4.2: Changes in genotype can result in changes in phenotype.

(EK3.C.1)

1. Mutations
Mutations are changes to the genome that can affect phenotypes. Mutations can be
positive, negative, or neutral in terms of their affect on an organisms phenotype.
They are caused by exposure to certain chemicals (mutagens), high energy
radiation, and through DNA replication (in humans the post-error checking rate
of mutations is approximately 1 per 1 billion replicated bases).

9
 DNA-level mutations:
Substitutions: Change of one base to another base. Can affect the structure of a
protein by changing one amino acid, or changing the placement of a stop codon.
Called a point mutation because it affects only one place in the genome.
In/dels: insertion or deletion of a DNA base. Can affect the structure of a protein by
changing the amino acid sequence of all subsequent amino acids following the
in/del, or changing the placement of a stop codon. Called a frame shift mutation
because it affects the reading frame of the ribosome.
Chromosomal mutations:
Mistakes that result in large-scale rearrangement of chromosome sections:
Duplication
Deletion
Inversion
Translocation
Cell division mutations:
Mistakes that occur during cell division resulting in extra/missing chromosomes
(Downs Syndrome: trisomy 21, Turners Syndrome: monosomy X), or entire
sets of chromosomes (polyploidyreally only tolerated in plants)

Evolution requires variation. Mutations are the ultimate source of all genetic
variation.

The fitness of a mutant is not just a function of its genome. The environment
determines how well
adapted a mutant is.
Ex. Heterozygote advantage and sickle cell anemia. The sickle cell allele is at a higher
frequency in areas where malaria is endemic. Heterozygotes for sickle cell are at
10
 an advantage over homozygous non-sickle cell individuals in those areas. In the
rest of the world, the heterozygote advantage for sickle cell is not present because
malaria is not endemic, and there are other, limiting effects on heterozygote
physiology.

4.3: Viral replication results in genetic variation, and viral

infection can introduce genetic variation into the hosts.
(EK3.C.3)

1. Viral Genetics
Viruses are obligate intracellular parasites. Viruses are sub-cellular, and as such are
generally not considered to be living. They are only active when infecting and
replicating inside a host cell, and do not have any external metabolism.

Viral anatomy consists of a nucleic acid (DNA or RNA) inside of a protein coat.
Some eukaryotic viruses also posses an external lipid envelope.

The generalized viral life cycle (many variations on this theme):

Infection: the virus is able to transfer its genetic information in to a host cell.
Viruses are specific to particular cell types. This is due to the specificity of the
receptors they use to attach to host cells.

Replication: the viral genome (and viral polymerases if necessary) utilize host cell
materials to manufacture viral proteins and replicate the viral genome.

Self-assembly: new viral particles are spontaneously assembled from their

components.
11
Release: the new viral particles are released in to the environment to infect new cells.

Viruses can evolve very rapidly.

Viral polymerases have higher error rates than cellular polymerases. This produces
more spontaneous mutations per replication than what is seen in cellular systems.
Since more variants are produced every generation, there is a higher likelihood of
variants being produced who are better adapted for their environment (which
could include features like evading the host immune system).

Additionally, when different strains of a virus co-infect the same cell, they can
recombine in to variants that have genetic information from each strain. This is
the major concern with bird and swine flu.

HIV is an interesting viral example:

HIV is a type of retrovirus, a class of viruses that contain an RNA genome. When
it infects a cell, HIV uses a viral reverse transcriptase to make a DNA copy of its
RNA genome. The DNA version of the HIV genome is then spliced in to the host
cell genome, where it produces new viruses through the host cells normal protein
synthesis machinery (RNA polymerase and ribosomes).

HIV infects one type of immune system cell (the Helper T-Cell), which leads to
an eventual collapse of the infected persons immune system, and the development
of AIDS. The body is then susceptible to a series of opportunistic infections,
which are invariably fatal if not treated.

12
 Modern treatments for AIDS include a variety of antiviral drugs that interfere
with the HIV life cycle.

Viruses are effective at transferring genetic information.

Viruses serve as vectors for delivering genetic information. Usually this is the
viruses own genetic information, but sometimes viruses can be packaged with
DNA from the host cell genome (transduction). An active avenue of research is
looking at using customized viruses to deliver functional genes to populations of
cells with genetic defects.

There is no cure for a viral infection

The ability of a virus to remain dormant in a host cells genome enables a viral
infection to remain latent for long periods of time, before signals trigger the re-
emergence of the active virus. In mammals, the immune system recognizes and
rapidly responds to recurring viral infections, as long as the virus hasnt mutated
to the point that the immune system can no longer recognize it.

4.4: In eukaryotes, heritable information is passed to the next

generation via processes that include the cell cycle and
mitosis or meiosis plus fertilization. (EK3.A.2)

1. Mitosis
All cells reproduce through division (binary fission in bacteria)

The Cell Cycle describes the major events of the life of a cell.
Interphase vs. M-phase:

13
 Interphase is ~95% of the cell cycle:
G1: The cell is growing and (if it is going to divide), preparing for DNA
replication.
S: The cell replicates its DNA.
G2: The cell repairs replication errors and prepares for division
M-phase: Cell division.
G0: permanent interphase that non-dividing cells exist in until death.

Through the cell cycle, cells are able to serve the life functions of growth (making
more cells), repair (replacing damaged cells), and reproduction (making new
generations of cells)

The behavior of chromosomes during the cell cycle allows for heritability.

Mitosis produces two genetically identical daughter cells:

The events of mitosis are structured to transmit a complete genome to both
daughter cells. The stages of mitosis occur as a continual process.
Prophase: the replicated chromosomes condense. Chromosomes are tightly wound
DNA molecules, wrapped around histone proteins. Packing makes moving easier.
Prometaphase: The nuclear envelope breaks down.
Metaphase: The chromosomes align at the middle of the cell, attached to the
mitotic spindle
Anaphase: The chromosomes are separated at the centromere and migrate to
opposite poles of the cell.
Telophase: the chromosomes decondense, a nuclear envelope reforms around
each set.
Cytokinesis: the cell membrane is cleaved, producing two cells.
14
2. Cell Cycle Control
Mitosis is under strict cellular control. In order to move through the stages of the
cell cycle, a cell needs to pass through a series of checkpoints (internal conditions
must be appropriate).

Cancer: the result of loss of the cell-cycle controls in a cell. Will inevitably result in
the death of the organism.

Cells are able to stop dividing, start dividing again if given proper signals from other
cells, and remain at particular stages of the cell cycle for long periods of time.

The control of the cell cycle is accomplished through the action of proteins:
Example: Mitosis Promoting Factor (MPF)- controls the Mitosis checkpoint of the
cell. If MPF is not present, a cell will not enter mitosis. MPF is the result of the
combination of two other proteins. One (Cdk- cyclin dependent kinase) is always
present in the cell. The other one (cyclin) is only made once a cell has met the
criteria needed to enter mitosis.

External signals also control the cell cycle:

Example: Platelet Derived Growth Factor (PDGF)- Released at the site of tissue
injury by platelets. Causes non-dividing cells to begin dividing to repair damaged
tissue.

3. Meiosis
Meiosis produces cells with half of the normal amount of genetic material.
15
Sexual reproduction requires that two haploid cells combine to produce one
diploid cell during fertilization. Meiosis is the process that produces these
haploid gametes.

The events of meiosis are similar to those of mitosis with a few key differences:
There are two sequential rounds of cell division: Cells progress through meiosis 1
(PMAT1) and then through meiosis 2 (PMAT2) without replicating DNA in-
between. After meiosis 1, one cell has become two cells. After meiosis 2, each of
the two cells produced in meiosis 1 have become two cells. At the end of meiosis,
one diploid cell has become four haploid cells.

Crossing over: During prophase 1, the homologous pairs of chromosomes physically

associate with each other and exchange genetic material. This results in every
chromosome being a unique combination of the genetic material from both
members of the homologous pair.

Independent Assortment: During metaphase 1, chromosomes line up in the middle

of the cell still attached to their homologs. The orientation of one pair of
chromosomes has no effect on the orientation of any other pair.

Meiosis and the sexual life cycle generate tremendous variation.

Variation due to independent assortment: expressed as 2^n. In humans =
~8,000,000 possible orientations of our 23 chromosomes.

Variation due to fertilization: expressed as (2^n)(2^n). In humans =

~70,000,000,000,000 possible combinations.
16
 Variation due to Crossing Over: functionally infinite combinations of genetic
information.

3. Chromosomal Disorders
Many Genetic Disorders are explained by mistakes during the cell cycle.

Non-disjunction:
Due to problems with the separation of chromosomes during meiosis, cells can be
produced with extra chromosomes or missing chromosomes. The majority of
these errors are fatal to the developing organism, but some are tolerated, leading
to diseases.

Ex. Downs Syndrome: Results from having three copies of chromosome 21. Has
wide-ranging effects on the physiology of the person.

Ex. Klinefelters Syndrome: Results from having two X chromosomes and one Y
chromosome. Individuals are phenotypically male but have some female
secondary sexual characteristics, and are sterile.

Genetic tests are available, but pose ethical questions.

Karyotype analysis: isolation and visualization of an individuals chromosomes.
Can be used to diagnose non-disjunction related genetic conditions.

Modern genetic tests can also determine a host of other genetic diseases that are
not able to be visualized on a karyotype (Ex. Huntingtons Chorea)

17
 This information can be used by parents to determine if they would like to
continue a pregnancy, or prepare for a baby with a medical condition.

There are major ethical considerations that accompany these decisions. Questions
of reproductive rights, and issues of ownership of genetic information, privacy,
and historical contexts (e.g. eugenics).

4.5: The chromosomal basis of inheritance provides an

understanding of the pattern of passage (transmission) of
genes from parent to offspring. (EK3.A.3)

1. Mendelian Genetics
The behavior of chromosomes explains the inheritance of traits. Since genes are on
chromosomes, the movements of chromosomes during meiosis will determine the
inheritance of the genes they contain.

The mathematical analysis of heredity was originally developed by Gregor Mendel,

who analyzed the inheritance of traits in pea plants.

Mendel developed several major concepts to explain his observations, which have
since been related to the behavior of chromosomes, and the relationship between
genes and phenotypes:

Reminder- Genotype vs. Phenotype

Genotype: the alleles that an organism has for a particular trait. Homozygous vs.
Heterozygous

18
Phenotype: the trait that an organism shows.

Sexually reproducing organisms have two alleles for any trait:

One allele is inherited from each parent.

Dominant vs. recessive alleles:

the disappearance and then reappearance of certain traits is explained by the fact that
these traits are recessive. When an allele for a recessive trait is present along
with an allele for a dominant trait, the dominant trait will be expressed. In order
for a recessive trait to be expressed, both alleles have to be for the recessive trait.

Segregation of alleles:
During meiosis, each gamete will receive one of the organisms two alleles. Each
organism will produce an equal number of gametes with each allele.

Independent Assortment:
During meiosis, the segregation of one allele has no effect on the segregation of
any other allele, as long as the alleles are on separate chromosomes (unlinked).

Using these concepts, the inheritance of different characteristics can be predicted

based on the
proportions of offspring who show different phenotypes for those characteristics.

2. MATH SKILLS: Genetics Probabilities

19
The inheritance of unlinked genes are independent events (similar to multiple flips of
a coin).

The probability of multiple independent events occurring together is equal to the

product of the probabilities of each individual event.

Using this, we can determine the probability of a particular group of offspring being
produced from a particular cross by determining the individual probabilities for
each trait and then multiplying them together.

This only works for unlinked genes.

Sample Problem:
In pea plants the gene for wrinkled seed pods (R) is dominant to the gene for
smooth pods (r), and the gene for yellow seeds (Y) is dominant to the gene for
green seeds (y).
A heterozygous wrinkled, yellow pea plant is crossed with a homozygous smooth,
green pea plant. What fraction of its offspring will be smooth and yellow?

Cross: RrYy x rryy

Offspring: rrY_ * = 1/4

Also, given the limited genotypes for organisms, each type of cross produces
characteristic genotypic and phenotypic ratios of offspring.

Sample Problem:
In a cross between two organisms with the following genotypes:
20
 AaBBCcddEe x aaBbCcDdEe
What is the probability of getting offspring with the genotype aaBbccDdEE?

x x x x = 1/128

4.6: The inheritance pattern of many traits cannot be explained

by simple Mendelian genetics. (EK3.A.4)

1. Mendelian Extensions
Many traits are not inherited in simple Mendelian ratios. These traits can involve a
lot of different
aspects of genetics and physiology, but will always affect the ratios of offspring that
are shown.
Incomplete Dominance/Codominance: The heterozygote has a different phenotype
than either homozygote (ex. Snapdragon color, human blood type)
Multiple alleles: Traits have more than two alleles (ex. Human ABO blood types)

2. Non-Mendelian Traits
Certain modes of inheritance are non-mendelian.

Many traits are linked to certain chromosomes. Mendelian ratios only refer to
situations where each gene is inherited independently of each other.
The inheritance of these traits depends on the inheritance of these chromosomes.

Much of this work was done by TH Morgans lab at Columbia in the early 1900s.

21
Sex linkage: Traits are on the X chromosome. Males will show the recessive
characteristic much more often than females. (Ex. white eyes, color blindness)
Sex-limited traits: Traits that are only expressed in one sex. (ex. milk production,
pattern baldness)
Linked genes: Genes that are on the same chromosome will be inherited together,
except when crossing over results in recombination. Can be identified by their
divergence from Mendelian expected ratios of offspring.
Linkage analysis: Can be used to investigate the distance between linked genes on
the same chromosome. The greater the distance between two genes on a
chromosome, the more often crossing over will occur between them (the greater
the frequency of recombinants).

Some genes are not inherited through the nuclear genome of a cell.

Non-nuclear inheritance refers to the inheritance of genes in the chloroplast and

mitochondrial genomes.

The chloroplasts and mitochondria of cells are randomly assorted when daughter
cells and gametes are being produced, so the traits they carry are not inherited via
Mendelian mechanisms.

Ex. All mammals inherit their mitochondria from their mothers egg cell
(matrilineal inheritance). This can be used to track human ancestry and
historical migration.

22
4.7: Biological systems have multiple processes that increase
genetic variation. (EK3.C.2)

1. Generation of Variation
All lineages of life have modes of generating genetic variation.

Mistakes during DNA replication:

Error proofing of DNA is not 100% accurate (thermodynamically impossible). So
all DNA will contain some number of mutations due to replication.

Horizontal transfer of genetic material in bacteria:

Refers to the transmission of genes between members of the same generation of
bacteria.
Transformation: the uptake of DNA directly from the environment.
Transduction: The transfer of DNA via viral infection.
Conjugation: The transfer of DNA through cell-cell contact
Transposition: The replication and movement of DNA segments separate from
replication of the genome.

Sexual reproduction:
Meiosis and the random nature of fertilization produce functionally infinite
combinations of genetic material in sexual reproducing organisms. Sexual
reproduction has evolved independently in all major eukaryotic lineages (protists,
fungi, animals, and plants). The unifying characteristic is that haploid cells are
produced, which unite during fertilization to form a diploid zygote.

23
4.8: Gene regulation results in differential gene expression,
leading to cell specialization. (EK3.B.1)

1. Gene Regulation
Regulatory DNA sequences control transcription rates by interacting with regulatory
proteins (transcription factors):

Promoter: sequences of DNA that precede the start of a transcribed gene.

Recognized by transcription factors and RNA polymerase. The presence of
transcription factors on the promoter make transcription possible.

Enhancers: sequences of DNA further upstream than the promoter. The presence of
transcription factors on these regions increase the rate of transcription (up
regulation)

Regulatory RNA elements and regulatory proteins. Produced by regulatory genes,

and associate with
regulatory DNA sequences to allow for transcription.

Regulatory DNA sequences serve as molecular switches. When the required

transcription factors are
present, the switch is on, and transcription occurs. When the required factors are
not present, the switch is off, and no transcription occurs.

2. Prokaryotic Gene Regulation

Prokaryotes control gene expression almost entirely by controlling transcription.

24
The lack of a nucleus makes this efficient.

Operons:
Groups of genes (structural genes) that all contribute to a specific metabolic
processes (e.g. digestion of lactose, synthesis of tryptophan).

Transcription of all of the genes is regulated by a single promoter.

Repressor protein: a regulatory protein that allows/blocks transcription by

physically associating/disassociating with a region of the promoter called the
operator.

The modulation between the active and inactive forms of the repressor protein is
accomplished through an allosteric interaction with the molecules that are acted
upon by the particular metabolic pathway.

The operational logic of the operon will depend on how necessary the product of
the metabolic pathway it controls is for the cell.

Ex. The Lac Operon:

Involved in the digestion of lactose.
inducible: usually off, only on when lactose is present in the cell.
The binding of lactose to the repressor protein causes its conformation to change and
it to dissociate from the operator.

Ex. The Trp Operon:

Involved in the synthesis of tryptophan
25
repressible: Usually on, only off when there is an excess of tryptophan present
in the cell.
The binding of tryptophan to the repressor protein causes its conformation to
change and it to associate with the operator.

Upregulation: The binding of other regulatory proteins to the operator can increase
the rate of transcription of the structural genes to many times above the baseline
level.

Ex. The Catabolite Activator Protein: When particular energy-producing

molecules are low, the cAMP molecular signal associates with the CAP protein.
This CAP/cAMP complex associates with the promoter of operons involved in
energy production (e.g. the lac operon) and increases the amount of transcription
by directly recruiting RNA polymerase to the promoter.

Constitutive genes: Genes that are constantly transcribed and are not under major
regulatory control. Ex. Ribosomal RNA genes.

3. Eukaryotic Gene Regulation

Eukaryotes control gene expression at steps in the process

Pre-Transcriptional controls:
Access to genes: winding and unwinding of DNA around histone proteins is
controlled by enzymatic acetylation and de-acetylation of tail regions of the

26
 histones. Different types of cells will have different regions of the genome
accessible for transcription.

Regulation of transcription: Eukaryotes have a wide variety of transcription

factors that control transcription (activators and repressors). Different types of
cells will have different collections of transcription factors present, to allow the
transcription of certain accessible genes and block transcription of others.

Post-Transcriptional/Pre-Translational controls:
Post-Transcriptional processing: Poly-Adenylation, 5 capping, and intron
splicing all must occur to produce a functional transcript.
alternate splicing: combining different exons from the same transcript to produce
multiple gene products from one transcript.

RNA interference (RNAi): the blocking of transcription by small interfering RNA

molecules, which bind to specific transcripts and keep the ribosome from being
able to translate them.

Post-Translational controls:
Targeting of polypeptides: signals on the polypeptide determine if the polypeptide
will be made in the cytoplasm, or if the ribosome will associate with the ER.

Ubiquinone/Proteosome degradation: Tagging of a protein by a ubiquinone

molecule will cause the protein to be degraded by a proteasome complex.

4. Gene Regulation ! Phenotype

27
The control of gene expression leads to the control of phenotypes.

Phenotypes are the result of protein interactions within the cell. By controlling the
production of proteins, cells influence the manifestation of particular phenotypes.

Multicellular organisms control cellular differentiation through differential gene

expression.

The reason that different types of cells are present in a multicellular organism are
because different cell types are expressing different genes, which leads to their
differing phenotypes.

Even genetically identical organisms can have different phenotypes due to differences
in gene expression.

Ex. Cloned mammals have noticeable phenotypic differencesso do identical twins.

4.9: A variety of intercellular and intracellular signal

transmissions mediate gene expression. (EK3.B.2)

1. Signal Control of Gene Expression

Signals that are transmitted between and within cells affect gene expression:
Example: yeast mating- two mating types: Alpha and a. Each mating type
produces a pheromone that interacts with receptors on the cell membrane of the
opposite mating type. When this interaction occurs, the genes that control the
development of the mating structure (the shmoo) in the yeast are activated, and
the two mating types fuse together in a fertilization event.

28
Signals that are transmitted between and within cells affect cell function:
Example: Hox Genes: present in all animals. Control the development of specific
sections of an animals body. The presence of Hox transcription factors activate
the genes needed to begin the development of a particular segment of an animals
body (morphogenesis and differentiation).

4.10: Environmental factors influence the expression of the

genotype in an organism. (EK4.C.2)

1. Environmental Effects on Phenotype.

Phenotype is a product of genotype AND environment:
The genome is not a blueprint. It is more like a recipe.

An organisms environment has a major role in determining the organisms

phenotype.

The environment can determine phenotype directly:

Examples: Hydrangea flower color and soil pH, sex determination in reptiles,

The genome can respond to the environment:

Example: Seasonal changes in fur color, height and weight in humans, tanning
response.

Plasticity: The interactions between environment and genome can be very complex.
It becomes difficult to draw the nature vs. nurture line in many cases.

29