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Chapter 1
Life is recognized by what living things do:
Order
Evolutionary Adaptation
Regulation
Growth and Development
Reproduction
Response to Environment
Energy Processing
Biological Hierarchy
Biosphere - all environments on Earth that are inhabited by life: includes most land regions,
bodies of water, and the lower atmosphere
Ecosystem - all living things in a particular area along with their non-living surroundings
Community - all organisms that inhabit an ecosystem
Population - all individuals of a species living within a specified area
Organisms - individual living things
Organ Systems/Organ - body part of two or more tissues that carries out a particular
function
Tissues - organized group of cells of a particular type
Cell - fundamental unit of a living organism
Organelles - functional, membrane enclosed components that makeup cells present in
eukaryotes
Molecules - composed of atoms and give rise to molecular structure
Biological Hierarchy
Emergent Properties - properties emerge that were not in the preceding level. Result from
arrangement and interaction of parts within a system as complexity increases. eg) thoughts
and memories are emergent properties of nerve cells in the brain
Reductionism - taking apart a complex system to simpler components that are more
manageable to study
System - combination of components that function together
Systems Biology - construct models for the dynamic behaviour of whole biological systems.
Successful models enable biologists to predict how a change in one or more variables will
affect other components and the whole system. Inventory parts; application of reductionism
Ecosystem Dynamics
- cycling of nutrients (materials: plants > soil)
- flow of energy from sunlight to producers to consumers
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Structure and Function are closely related
eg) leaf - thin flat shape maximizes captured sunlight
Cells are the basic units
-enclosed by membrane
-uses DNA as genetic information
-cells divide; basis of reproduction
-life comes from pre-existing life
Eukaryotic Cell - organelles and nucleus
Prokaryotic Cell - simpler and smaller with no nucleus; Bacteria/Archea
DNA:
Deoxyribonucleic Acid - chemical substance of genes
Genes - units of inheritance
Genome - library of genetic instructions within DNA that an organism inherits from its
predecessors
DNA genes control protein production using RNA
Nucleotides are transcribed into mRNA and translated into proteins
Feedback Mechanisms - self-regulation of biological processes
Negative feedback
Positive feedback
Evolution
Biology's core theme
process of change that has transformed life on Earth from its earliest beings to the
organisms present today
organisms are descended from common ancestors
accounts for the unity and diversity of life
Classifying Life
Taxonomy - names and classifies organisms into groups
Domain, Kingdom, Phylum, Class, Order, Family, Genus, Species
Domain:
Domain Bacteria - prokaryotes
Domain Archea - prokaryotes
Domain Eukaryote
Eukaryote Kingdoms: Plantae
Anamalia
Fungi
Protista
Charles Darwin
-Species showed "descent with modification" from common ancestors
-natural selection is the mechanism behind "descent with modification"
-Darwin's theory explained duality and diversity within evolution
Scientific Inquiry
Discovery/Descriptive Science - inductive reasoning
Hypothesis-Based Science - predictions that can be tested
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Deductive Reasoning - uses general premises to make specific predictions. Uses "ifthen"
reasoning.
Theory - an explanation broad in scope, generates new hypotheses and is supported by
large body of evidence
Chapter 3 - Water
The Molecule that Supports All Life
• All living organisms require water more than any other substance
• Most cells are surrounded by water, and cells themselves are about 70-95% water
• The abundance of water is the main reason the Earth is habitable
Polar Molecule - two ends have opposite charges
Properties:
Cohesive Behaviour
Ability to moderate temperature
Expansion on freezing
Versatility as a solvent
Cohesion - binding together of like molecules
water has hydrogen bonding
transports water up plants (evaporated water pulls other molecules upwards)
Adhesion - attraction between different molecules
clinging of one substance to another
water to cell walls of plants by H-bonding counters gravity
Surface Tension - measure of how difficult it is to break or stretch the surface of a liquid
Moderation of Temperature - water absorbs heat from warmer air and releases stored heat
to cooler air; can have large amount of heat with only a slight change in its own temperature
Specific Heat Capacity of water is 1 cal/g/ C
Solution - liquid that is homogeneous mixture of substances
Solvent - dissolving agent
Solute - substance dissolved
Aqueous Solution - solution in which water is a solvent
Hydrophilic Substance - has affinity for water
Hydrophobic Substance - does not have affinity for water
oil molecules are hydrophobic because of their non-polar bonds
Ch 8 - The Energy of Life
• The living cell is a mini chemical factory where thousands of reactions occur
• The cell extracts energy and applies energy to perform work
Metabolism
- the totality of an organism's chemical reactions
- emergent property; interactions between molecules within the cell
- transforms matter and energy
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metabolic pathway begins with a specific molecule and ends with a product
- each step is catalyzed by a specific enzyme
Feedback mechanisms allow biological processes to self-regulate
• Negative feedback means that as more of a product accumulates, the process that creates
it slows and less of the product is produced
• Positive feedback means that as more of a product accumulates, the process that creates it
speeds up and more of the product is produced
• Catabolic pathways - release energy by breaking down complex molecules into simpler
compounds
eg) Cellular respiration - breakdown of glucose in the presence of oxygen
• Anabolic pathways - consume energy to build complex molecules from simpler
eg) The synthesis of protein from amino acids
Bioenergetics - the study of how organisms manage their energy resources
Energy - the capacity to cause change
- can be converted from one form to another
• Kinetic energy -motion
• Heat (thermal energy) -random movement of atoms or molecules
• Potential energy -related to location or structure
• Chemical energy -potential energy available for release in a chemical reaction
The Laws of Energy Transformation
• Thermodynamics is the study of energy transformations
• A closed system is isolated from its surroundings
• In an open system, energy and matter can be transferred between the system and its
surroundings eg) Organisms are open systems
first law of thermodynamics: the energy of the universe is constant:
- Energy can be transferred and transformed; it cannot be created or destroyed
second law of thermodynamics:
- Every energy transfer or transformation increases the entropy (disorder) of the universe.
Some energy is converted to an unusable form such as heat.
Free-Energy Change
• living system's free energy is energy that can do work when temperature and pressure
are uniform, as in a living cell
change in free energy (∆G)
∆G= ∆H -T∆S
enthalpy,change total energy (∆H)
change in entropy (∆S)
temperature in Kelvin (T)
Spontaneous processes
- occur without energy input; they can happen quickly or slowly
- to occur without energy input, it must increase the entropy of the universe
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- negative ∆G
- can be harnessed to do work
Cells create ordered structures from less ordered materials
Organisms replace ordered forms of matter and energy with less ordered forms
Energy flows into an ecosystem in the form of light and exits in the form of heat
• An exergonic reaction proceeds with a net release of free energy and is spontaneous
• An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous
Equilibrium and Metabolism
• Reactions in a closed system eventually reach equilibrium and then do no work
• Cells are open systems experiencing a constant flow of materials (no equilib.)
• A defining feature of life is that metabolism is never at equilibrium
• A catabolic pathway in a cell releases free energy in a series of reactions
To do work, cells manage energy resources by energy coupling, the use of an exergonic
process to drive an endergonic one.
A cell does three main kinds of work:
- Chemical
- Transport
Mechanical
ATP - adenosine triphosphate
- powers cellular work by coupling exergonic reactions to endergonic reactions
- the cell's energy shuttle
- composed of ribose sugar, adenine, and three phosphate groups
- mediates most energy coupling in cells
- drives endergonic reactions by phosphorylation, transferring a phosphate group to some
other molecule, such as a reactant
• The recipient molecule is now phosphorylated
- renewable resource that is regenerated by addition of a phosphate group to
adenosine diphosphate (ADP)
Activation Energy and Enzymes
- Enzymes catalyze reactions by lowering the EA barrier
- Enzymes do not affect the change in free energy (∆G); instead, they hasten reactions that
would occur eventually
- The reactant that an enzyme acts on is called the enzyme's substrate
- The enzyme binds to its substrate, forming an enzyme- substrate complex
- The active site is the region on the enzyme where the substrate binds
- Induced fit of a substrate brings chemical groups of the active site into positions that
enhance their ability to catalyze the reaction
Allosteric Activation and Inhibition
- Each enzyme has active and inactive forms
- The binding of an activator stabilizes the active form of the enzyme
- The binding of an inhibitor stabilizes the inactive form of the enzyme
Feedback inhibition - end product of a metabolic pathway shuts down the pathway
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• Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more
product than is needed
Feedback mechanisms allow biological processes to:
self-regulate, react, be responsive, which are characteristics of living
• Negative feedback means that as more of a product accumulates, the process that creates
it slows and less of the product is produced
• Positive feedback means that as more of a product accumulates, the process that creates it
speeds up and more of the product is produced
Chapter 9 - Life is Work
Ecosystem Dynamics
- Cycling of nutrients - materials acquired by plants eventually return to the soil
- The flow of energy from sunlight to producers to consumers
Catabolic Pathways and Production of ATP
• The breakdown of organic molecules is exergonic
• Aerobic respiration consumes organic molecules and O2 and yields ATP
• Anaerobic respiration is similar to aerobic but consumes compounds other than O2
• Cellular respiration includes both aerobic and anaerobic respiration but is often used to
refer to as aerobic respiration
• carbohydrates, fats, and proteins are all consumed as fuel
C6H12O6 + 6 O2 6
CO2
+ 6 H2O + Energy (ATP + heat)
Redox Reactions
• Chemical reactions that transfer electrons between reactants are redox reactions
• The transfer of electrons during chemical reactions releases energy stored in organic
molecules
• This released energy is ultimately used to synthesize ATP
• In oxidation, a substance loses electrons, or is oxidized
• In reduction, a substance gains electrons, amount positive charge is reduced
• The electron donor is called the reducing agent
• The electron receptor is called the oxidizing agent
• During cellular respiration, the fuel (such as glucose) is oxidized, and O2 is reduced
Stepwise Energy Harvest
(via NAD+ and the Electron Transport Chain)
• In cellular respiration, glucose and other organic molecules are broken
• Electrons from organic compounds are transferred to a coenzyme, NAD+
• As an electron acceptor, NAD+ functions as an oxidizing agent
• Each NADH (the reduced form of NAD+) represents stored energy that is tapped to
synthesize ATP
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• NADH passes the electrons to the electron transport chain (ETC)
• Unlike an uncontrolled reaction, the ETC passes electrons in a series of steps
• O pulls electrons down the chain in an energy- yielding tumble
• The energy yielded is used to regenerate ATP
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Cellular Respiration Process
- Glycolysis (breaks down glucose into two molecules of pyruvate)
- The citric acid cycle (completes the breakdown of glucose)
- Oxidative phosphorylation (accounts for most of the ATP synthesis)
• Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular
respiration
• A smaller amount of ATP is formed in glycolysis and the citric acid cycle by substrate-level
phosphorylation
Glycolysis
("splitting of sugar")
- breaks down glucose into two molecules of pyruvate
- occurs in the cytoplasm and has two major phases:
1) Energy investment phase
2) Energy payoff phase
Citric Acid Cycle - Kreb's Cycle
• takes place within the mitochondrial matrix
• oxidizes organic fuel derived from pyruvate
generates 1 ATP, 3 NADH, and 1 FADH2 per turn
• The citric acid cycle has eight steps, each catalyzed by a specific enzyme
• The acetyl group of acetyl CoA joins the cycle by combining with oxaloacetate, forming
citrate
• Cycle decomposes the citrate back to oxaloacetate
• The NADH and FADH2 produced by the cycle relay electrons extracted from food to the
electron transport chain
Pathway of Electron Transport
• ETC is in the cristae of the mitochondrion
• components mostly proteins
• carriers alternate reduced and oxidized states as they accept and donate electrons
• Electrons drop in free energy as they go down the chain
• Electrons are finally passed to O2, forming H2O
• Electrons are transferred from NADH or FADH2 to the electron transport chain
• Electrons are passed through a number of proteins including cytochromes (each with an
iron atom) to O2
• The electron transport chain generates no ATP
• The chain's function is to break the large free-energy drop from food to O2 into smaller
steps that release energy in manageable amounts
Chemiosmosis
• chemiosmosis - the use of energy in a H+ gradient to drive cellular work
• ETC causes proteins to pump H+ from the mitochondrial matrix to the intermembrane
space
• H+ moves back across the membrane, passing through channels in ATP synthase
• ATP synthase uses the exergonic flow of H+ to drive phosphorylation of ATP
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• The energy stored in a H+ gradient across a membrane couples the redox reactions of the
electron transport chain to ATP synthesis
• The H+ gradient is referred to as a proton-motive force, emphasizing its capacity to do
work
ATP Production
Breakdown of organic molecules is exergonic - energy generated
Cellular Respiration
• During cellular respiration, most energy flows in this sequence:
glucose - NADH - electron transport chain - proton-motive force - ATP
• About 40% of the energy in a glucose molecule is transferred to ATP
• generates about 38 ATP
• requires O2 to produce ATP
• Glycolysis can produce ATP with or without O2 (aerobic or anaerobic conditions)
Anaerobic Respiration
• In the absence of O2, glycolysis couples with fermentation or anaerobic respiration to
produce ATP
• Anaerobic respiration uses an electron transport chain with an electron acceptor other
than O2, for example sulfate
• Two common types are
alcohol fermentation
lactic acid fermentation
• Fermentation is a partial degradation of sugars that occurs without O2
• Fermentation uses phosphorylation instead of an ETC to generate ATP
• Fermentation consists of glycolysis plus reactions that regenerate NAD+
• Both processes use glycolysis to oxidize organic fuels to pyruvate
• Cellular respiration produces 38 ATP per glucose molecule
• Fermentation produces 2 ATP per glucose molecule
Ch. 10 Photosynthesis
Photosynthesis - is the process that converts solar energy into chemical energy
Autotrophs
• sustain themselves without eating anything derived from other organisms
• produce organic molecules from CO2 and other inorganic molecules
• Almost all plants are photoautotrophs, using the energy of sunlight to make organic
molecules from H2O and CO2
• These organisms feed not only themselves but also most of the living world
• Photosynthesis occurs in plants, algae, certain other protists, and some prokaryotes
Heterotrophs
• obtain their organic material from other organisms
• are the consumers of the biosphere
• Almost all heterotrophs depend on photoautotrophs for food and oxygen
Photosynthesis converts light to chemical energy
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• Chloroplasts are structurally similar to (likely evolved from) photosynthetic bacteria
• This structural organization allows for the chemical reactions of photosynthesis
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Redox Reactions of Photosynthesis
The opposite of cellular respiration, in photosynthesis water is oxidized to oxygen and
carbon dioxide is reduced to glucose.
6 CO2 + 12 H2O + Light energy
Reactants:
6 CO2 12 H2O
Products:
C6H12O6
C6H12O6 + 6 O2
+ 6 H2O
6 H2O 6 O2
Two parts of photosynthesis
1) Light Reactions -in the thylakoids - "photo" part
Split H2O
Release O2
Reduce NADP+ to NADPH
Generate ATP from ADP by photophosphorylation
2) Calvin Cycle -in the stroma - "synthesis" part
forms sugar from CO2 using ATP and NADPH
begins with carbon fixation
incorporates CO2 into organic molecules
Chloroplasts:
are solar-powered chemical factories
thylakoids transform light energy into the chemical energy of ATP and NADPH
Light Energy
• electromagnetic spectrum - entire range of electromagnetic energy, or radiation
• Visible light consists of wavelengths (including those that drive photosynthesis) that
produce colors we can see
• Light also behaves as though it consists of discrete particles, called photons
Photosynthetic Pigments
• Pigments are substances that absorb visible light
• Different pigments absorb different wavelengths
• Wavelengths that are not absorbed are reflected or transmitted
• Leaves appear green because chlorophyll reflects and transmits green light
• Chlorophyll a is the main photosynthetic pigment
• Accessory pigments like chlorophyll b broaden spectrum used for photosynthesis
• Accessory pigments called carotenoids absorb excessive light that would damage
chlorophyll
Light and Pigments
• When a pigment absorbs light, it goes from a ground state to an excited state, which is
unstable
• When excited electrons fall back to the ground state, photons are given off, an afterglow
called fluorescence
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• If illuminated, an isolated solution of chlorophyll will fluoresce, giving off light and heat
Photosystems
• A photosystem consists of a reaction-center complex (a type of protein complex)
surrounded by light-harvesting complexes
• The light-harvesting complexes (pigment molecules bound to proteins) funnel the energy
of photons to the reaction center
• A primary electron acceptor in the reaction center accepts an excited electron from
chlorophyll a
• Solar-powered transfer of an electron from a chlorophyll a molecule to the primary
electron acceptor is the first step of the light reactions
There are two types of photosystems in the thylakoid membrane
• Photosystem II (PS II) functions first (the numbers reflect order of discovery) and is best
at absorbing a wavelength of 680 nm
• The reaction-center chlorophyll a of PS II is called P680
• Photosystem I (PS I) is best at absorbing a wavelength of 700 nm
• The reaction-center chlorophyll a of PS I is called P700
Linear Electron Flow
• Linear electron flow, the primary electron pathway, involves both photosystems and
produces ATP and NADPH using light energy
• A photon hits a pigment and its energy is passed among pigment molecules until it excites
P680
• An excited electron from P680 is transferred to the primary electron acceptor
• P680+ (P680 that is missing an electron) is a very strong oxidizing agent
• H2O is split by enzymes, and the electrons are transferred from the hydrogen atoms to
P680+, thus reducing it to P680
• O2 is released as a by-product of this reaction
• Each electron "falls" down an electron transport chain from the primary electron acceptor
of PS II to PS I
• Energy released by the fall drives the creation of a proton gradient across the thylakoid
membrane
• Diffusion of H+ (protons) across the membrane drives ATP synthesis
• In PS I (like PS II), transferred light energy excites P700, which loses an electron to an
electron acceptor
• P700+ (P700 that is missing an electron) accepts an electron passed down from PS II via
the electron transport chain
• Each electron "falls" down an electron transport chain from the primary electron acceptor
of PS I to the protein ferredoxin (Fd)
• The electrons are then transferred to NADP+ and reduce it to NADPH
• The electrons of NADPH are available for the reactions of the Calvin cycle
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Cyclic Electron Flow
• Cyclic electron flow uses only photosystem I and produces ATP, but not NADPH
• Cyclic electron flow generates surplus ATP, satisfying the higher demand in the Calvin
cycle
• Some organisms such as purple sulfur bacteria have PS I but not PS II
• Cyclic electron flow is thought to have evolved before linear electron flow
• Cyclic electron flow may protect cells from light-induced damage
Chemiosmosis in Chloroplasts and Mitochondria
• Chloroplasts and mitochondria generate ATP by chemiosmosis, but use different
sources
of energy
• Mitochondria transfer chemical energy from food to ATP
• Chloroplasts transform light energy into the chemical energy of ATP
• In mitochondria, protons are pumped to the intermembrane space and drive ATP
synthesis as they diffuse back into the mitochondrial matrix
• In chloroplasts, protons are pumped into the thylakoid space and drive ATP synthesis as
they diffuse back into the stroma
• ATP and NADPH are produced on the side facing the stroma, where the Calvin cycle
takes
place
• In summary, light reactions generate ATP and increase the potential energy of electrons
by moving them from H2O to NADPH
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The Calvin Cycle
Like the citric acid cycle, the Calvin cycle regenerates its starting material after molecules
enter and leave the cycle
• The cycle builds sugar from smaller molecules by using ATP and the reducing power of
electrons carried by NADPH
• Carbon enters the cycle as CO2 and leaves as a sugar named glyceraldehyde-3phosphate
(G3P)
• For net synthesis of 1 G3P, the cycle must take place three times, fixing 3 molecules of CO2
• The Calvin cycle has three phases:
-Carbon fixation (catalyzed by rubisco)
- Reduction
-Regeneration of the CO2 acceptor ribulose bis-phosphate (RuBP)
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Real-life Applications:
Taxol - found in bark of pacific yew tree
- can treat breast cancer
Carbon Capture - CO2 is stored underground
Carbon Fixation - use plants to convert CO2
- possible to change chemical composition of atmosphere by enzymes
Rubisco
Ribulose 1,5-bisphosphate carboxylase oxygenase
All molecules of Carbon have touched the enzyme rubisco at some point, which makes it an
extremely important enzyme.
G3P
Glyceraldehyde 3-phosphate
This molecule can be used to make glucose, sucrose, or other organic molecules
EXCEPTIONS TO STANDARD PHOTOSYNTHESIS
Environmental resistance
Alternative mechanisms of carbon fixation have evolved in hot, arid climates
To prevent dehydration, plants close their stromata to conserve H2O
This photosynthesis by reducing access to CO2 and causing O2 buildup
These conditions favor a seemingly wasteful process called photorespiration
Photorespiration
(most C3 plants: initial fixation of CO2 via rubisco forms G3P)
In photorespiration rubisco adds O2 instead of CO2 in the Calvin cycle
It consumes O2 and organic fuel releasing CO2 without ATP or sugar
It limits damaging products that build without the Calvin cycle
Problem: on a hot, dry day can drain up to 50% of carbon fixed by the Calvin cycle
Carbon storage
• C4 plants minimize the cost of photorespiration by incorporating CO2 into four-carbon
compounds in mesophyll cells
This requires the enzyme PEP carboxylase - has a higher affinity for CO2 than rubisco does;
it can fix CO2 even when CO2 concentrations are low
These four-carbon compounds are exported to bundle-sheath cells, where they release CO2
that is then used in the Calvin cycle
CAM Plants
Some plants, like succulents, use crassulacean acid metabolism (CAM) to fix carbon
CAM plants open their stomata at night, incorporating CO2 into organic acids
Stomata close during the day
CO2 is released from organic acids and used in the Calvin cycle
Ch. 11 - Cell Communication
Signal Transduction Pathway
- steps where a signal on a cell's surface is converted into a specific cellular response
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- pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and
were modified later in eukaryotes
- Cells in a multicellular organism communicate by chemical messengers
Local Signals
- cell junctions can directly connect the cytoplasm of adjacent cells
- In local signaling, cells may communicate by direct contact, or cell-cell recognition
- animal cells have gap junctions, plant cells have plasmodesmata
- paracrine signaling and synaptic signaling involve secretion of chemical messages
local regulators are messenger molecules that travel short distances (neurotransmitter)
Long Distance Signalling
plants and animals use hormones to communicate to far-away target cells
Cell receiving signals go through three processes:
Reception
Transduction
Response
There are Three Main Types of Receptors in the Plasma Membrane
1) G protein-coupled receptors
- plasma membrane receptor that works with the help of a G protein
common protein structure/function
proteins in plasma membrane are partially inside and outside of cell
*transmembrane domain
-G protein acts as an on/off switch that signals yes/no response
switches operate through GTP phosphoreceptor - guanine triphosphate
If GDP is bound to the G protein, the G protein is inactive
This structural change is recognized by other receptors
there is a difference in total negative charge (less phosphate)
GDP is smaller and has different shape than GTP
-7 alpha helices hold protein together
connecting amino acids are looped and occur outside membrane
Receptor tyrosine kinases
- membrane receptors that attach phosphates to tyrosines
- can trigger multiple signal transduction pathways at once
- signaling molecule binds to site outside membrane
2 tyrosines bind together
change in structure
they are phosphorylated between tyrosines
- Catalytic Events - enzymes receive message and respond quickly
- the fully activated tyrosine kinase is a new protein
Ligand-gated Ion Channel Receptors
- acts as a gate when the receptor changes shape
- when a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such
as Na+ or Ca2+, through a channel in the receptor
• Receptors
- cell surface and cytoplasmic
• Transduction
proteins that transmit messages
small molecules that transmit messages
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• Calcium
• cAMP
• IP3
• DAG
Intracellular Receptors
• found in the cytosol or nucleus of target cells
• Small molecules or hydrophobic chemical messengers can readily cross the
membrane
and activate receptors
steroid and thyroid hormones
anabolic steroids have these receptors to change mRNA
• An activated hormone-receptor complex can act as a transcription factor, turning on
specific genes
Signal Transduction
change message to something the cell can understand
usually involves multiple steps
Multistep pathways can amplify a signal:
In signal amplification, catalytic enzymes called kinases give many
eg) allergies are caused by too many signals
Multistep pathways provide opportunities for regulation of response
What turns off signals are opposing molecules called protein phosphates
Regulation
Protein Phosphorylation and Dephosphorylation
In many pathways, the signal is transmitted by a cascade of protein phosphorylations
phosphorylation: protein kinases transfer phosphates from ATP to protein
dephosphorylation: protein phosphatases remove the phosphates from proteins
Protein kinases are key regulatory enzymes
- transfer the terminal phosphate from an ATP to the hydroxyl group of amino acids
- protein phosphatases remove phosphates from amino acids
Amino Acids
• 3 hydroxy amino acids are also part of the uncharged polar group
• R side chain contains a hydroxy group
• The hydroxy group can be chemically modified to contain a phosphate, which changes its
charge to negative from neutral and increases space it occupies
Addition of a phosphate to a hydroxyl amino acid will change its charge and its size
Proteins can be phosphorylated at many sites and at different times
This permits a change in protein activity without changing the genome (post-translation
modification)
Many diseases are caused by changes in protein kinase activity
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Tyrosine Kinase Signaling
Epidermal Growth Factor Receptor
EGFR
Modular system composed of:
1. Receptor/detector
2. Amplifier/modifier
3. Effectors
HUMAN KINOME
518 protein kinases encoded by the human genome
Their activities are similar; their sequences are similar (25%)
Their substrate specificity (ligand interaction) is different, therefore, sequence is different
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Small Molecules and Ions as Second Messengers
• first messanger: The extracellular signal molecule that binds to the receptor
• second messengers: small, nonprotein, water-soluble molecules or ions that spread
throughout a cell by diffusion
Cyclic AMP (cAMP)
• one of the most widely used second messengers
• Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in
response
to an extracellular signal
G-protein pathways are used by major extracellular signalling molecules
Calcium Ions and Inositol Triphosphate (IP3)
• Calcium ions (Ca2+) act as a second messenger in many pathways
• Calcium is an important second messenger because cells can regulate its concentration
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A signal relayed by a signal transduction pathway may trigger:
• an increase in calcium in the cytosol
• Pathways leading to the release of calcium involve inositol triphosphate (IP3) and
diacylglycerol (DAG) as additional second messengers
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Response:
Cell signaling leads to regulation of transcription or cytoplasmic activities
• output response: the cell's response to an extracellular signal
Nuclear and Cytoplasmic Responses
• signal transduction pathway leads to responses in the cytoplasm or in the nucleus
• Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by
turning genes on or off in the nucleus
• The final activated molecule may function as a transcription factor
The response time to a cell signal
-Activation of an enzyme
-Activation of transcription
How is diversity created from simple pathways?
• Multistep pathways have two important benefits:
-Amplifying the signal (and thus the response)
-Contributing to the specificity of the response
The Specificity of Cell Signaling and Coordination of the Response
• Different kinds of cells express different proteins
• Same signal can have different effects in cells with different proteins and pathways
• Pathway branching and "cross-talk" further help the cell coordinate incoming signals
Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
• Scaffolding proteins are large relay proteins to which other relay proteins are attached
• Scaffolding proteins can increase the signal transduction efficiency by grouping together
different proteins involved in the same pathway
Communication - You should now be able to:
1. Describe the nature of a ligand-receptor interaction and state how such interactions
initiate a signal-transduction system
2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligandgated ion channels
3. List two advantages of a multistep pathway in the transduction stage of cell signaling
4. Explain how an original signal molecule can produce a cellular response when it may not
even enter the target cell
5. Define the term second messenger; briefly describe the role of these molecules in
signaling pathways
6. Explain why different types of cells may respond differently to the same signal molecule
Ch.12 Cell Division
Theme: Cells are an organism's basic units of structure and function
Louis Pasteur - disproved spontaneous generation
Virchow - cells come from pre-existing cells
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Continuity of life - based on the reproduction of cells, or cell division
In multicellular organisms, cell division is balanced by cell death (apoptosis)
Cell growth is the outcome of proliferation and cell death
Cell death is not apoptosis - apoptosis is a method of controlled death
Study of Sea Urchin Eggs
same process of all eukaryotic cells
use sea urchins because the egg cells have features:
synchronous
start clock at sperm*egg
about 106 cells
Theme: Continuity of life based on heritable information in DNA
doubling genome
distributing to daughter cells
Flow Cytometer - measures cells in fluids
use laser to measure amount of DNA in one cell
laser passes through nucleus
DNA has range from1 copy to 2 copies because of the cell cycle
DNA fractions occur in "s" phase
In unicellular organisms, division of one cell reproduces the entire organism
Multicellular organisms depend on cell division for:
- Development from a fertilized cell
Growth
Repair
Cell Divison
• an integral part of the cell cycle, the life of a cell from formation to its own division
• results in daughter cells with identical genetic information, DNA
• A special type of division produces non-identical daughter cells
(gametes, or sperm and egg cells)
Cellular Organization of the Genetic Material
Genome
• All the DNA in a cell constitutes the cell's genome
• A genome can consist of one DNA molecule (common in prokaryotic cells) or a number of
DNA molecules (common in eukaryotic cells)
• DNA molecules in a cell are packaged into chromosomes
• Every eukaryotic species has a characteristic number of chromosomes in nucleus
Somatic cells - have two sets of chromosomes
Gametes - reproductive cells: sperm and eggs; have half chromosomes as somatic
Distribution of Chromosomes During Eukaryotic Cell Division
• In preparation for cell division, DNA is replicated and the chromosomes condense
• Each duplicated chromosome has two sister chromatids
chromatids separate during cell division
• The centromere is the narrow "waist" of the duplicated chromosome, where the two
chromatids are most closely attached
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Phases of the Cell Cycle
The cell cycle consists of
Mitotic phase (mitosis and cytokinesis)
Interphase
Interphase - cell growth and copying of chromosomes in preparation for division is about
90% of the cell cycle and can be divided into subphases:
G1 phase ("first gap")
S phase ("synthesis")
G2 phase ("second gap")
The cell grows during all three phases
chromosomes are duplicated only during the S phase
Mitosis is conventionally divided into five phases:
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase
Cytokinesis is well underway by late telophase
Mitosis
The Mitotic Spindle: A Closer Look
• The mitotic spindle - microtubules that control chromosome movement
• During prophase, assembly of spindle microtubules begins in the centrosome, the
microtubule organizing center
• An aster (a radial array of short microtubules) extends from each centrosome
• The spindle includes the centrosomes, the spindle microtubules, and the asters
• During prometaphase, some spindle microtubules attach to the kinetochores of
chromosomes and begin to move the chromosomes
• At metaphase, the chromosomes are all lined up at the metaphase plate, the midway point
between the spindle's two poles
• 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
• Nonkinetochore microtubules from opposite poles overlap and push against each other,
elongating the cell
Cytokinesis: A Closer Look
• Cleavage
• In animal cells, cytokinesis occurs by cleavage, forming a cleavage furrow
• In plant cells, a cell plate forms during cytokinesis
Binary Fission
• Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary
fission
• In binary fission, the chromosome replicates (beginning at the origin of replication), and
the two daughter chromosomes actively move apart
• In telophase, genetically identical daughter nuclei form at opposite ends of the cell
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The Cell Cycle Control System
The eukaryotic cell cycle is regulated by a molecular control system
• The frequency of cell division varies with the type of cell
• These cell cycle differences result from regulation at the molecular level
biochemical view - proteins
• 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
-A "motor" exists in all eukaryotic cells to drive cell division
Enzyme of division example:
Cyclin-Dependent Kinase 1
cyclin protein
cdk catalytic subunit
The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases
• Two types of regulatory proteins are involved in cell cycle control:
cyclins and cyclin-dependent kinases (Cdks)
• The activity of cyclins and Cdks fluctuates during the cell cycle
• MPF (maturation-promoting factor) is a cyclin- Cdk complex that triggers a cell's passage
past the G2 checkpoint into the M phase
Manfred Lohka
Proteolosis
- breaking proteins
done with enzymes called proteases
break peptide bond
Cdk does not cycle because it is always present
Cylin does cycle through mitosis
To stop a cell cycle, you could block activity at any point in the cycle
Applications in cancer
What happens when things go wrong?
The cell cycle wants to accurately divide and distribute to daughter cells
Checkpoints:
second set of enzymes check DNA present
are all enzymes for division present
what are the neighbouring cells doing / environment favourability
eg) if chromosome not present, cyclin protein will not be activated
Apoptosis
Controlled death
no cytoskeleton, no control of shape
Formation of Hand:
in reproduction, the hand is formed by division to form fingers
cells in between fingers die so they are not webbed
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Sunburn:
cells die through apoptosis because they were damaged
Skin cells peel off
capases - main proteases
nucleases - takes apart DNA
The Key Roles of Cell Division
The continuity of life
Apoptosis is programmed cell death - it is a controlled process
• By controlling apoptosis a dying cell does not damage neighboring cells
• During apoptosis the nucleus is degraded (DNA) and the mitochondria/chloroplasts are
degraded (energy)
• Apoptosis is important in shaping an organism during embryonic development
• The role of apoptosis in embryonic development was first studied in Caenorhabditis
elegans
The formation of a hand
•Proliferation
•Apoptosis
•Differentiation
Apoptotic Pathways and the Signals That Trigger Them
• Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis
• Apoptosis can be triggered by:
An extracellular death-signaling ligand
DNA damage in the nucleus
Protein misfolding in the endoplasmic reticulum
Mitochondria have two roles in the cell
Energy (life)
Apoptosis (death)
Apoptosis
• Apoptosis is essential for the development and maintenance of all animals
• Apoptosis may be involved in some diseases (for example, Parkinson's and Alzheimer's,
Cancer)
Loss of Cell Cycle Controls in Cancer Cells
• Cancer cells do not respond normally to the body's control mechanisms
• Cancer cells may growth without signal transduction pathways:
-They may make their own growth factor
-They may convey a growth factor's signal
without the presence of the growth factor
• Cancer cells may not undergo apoptosis
Bio 1010
You should now be able to:
1. Describe the structural organization of the prokaryotic genome and the eukaryotic
genome
2. List the phases of the cell cycle; describe the sequence of events during each phase
3. List the phases of mitosis and describe the events characteristic of each phase
4. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules,
nonkinetochore microtubules, and asters
5. Compare cytokinesis in animals and plants
6. Understand that cancer may arise from absence of apoptosis or an increase in cell
proliferation
Lipids
Fats
constructed from 2 smaller molecules: glycerol and fatty acid
glycerol is a 3-Carbon alcohol with hydroxyl group on each carbon
3 fatty acids joined to glycerol by an ester linkage, creating a triacylglycerol, or triglyceride
function: energy storage
mammals store fat in adipose cells adipose tissue also cushions vital organs and
insulates
body
Saturated fatty acids - maximum number of hydrogen atoms; no double bonds
Saturated fats - solid at room temperature
animal fats (stearic acid in butter)
Unsaturated fatty acids - one or more double bonds; cis DB causes bending in chain
Unsaturated fats - liquid at room temperature
plant and fish oils (oleic acid = olive oil)
Hydrogenation - convert unsaturated to saturated by adding hydrogen
- Hydrogenating vegetable oils = unsaturated fats with trans double bonds
Phospholipids
2 fatty acids + phosphate group at glycerol
tails hydrophobic
phosohate is hydrophilic
= aliphatic molecule
self-assemble into bilayer when added to water, as in cell membranes with hydrophobic
tails pointing to interior
Steriods
Lipids that are characterized by carbon skeleton with four fused rings
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Cholesterol - component in animal cell membranes (plants don't b/c have cell walls)
inserts into bilayer at fatty acid chain
clicker question: (chitin, fat, phospholipid, polysaccharide, cholesterol)
Which macromolecule contains the most fatty acid components?
A fat molecule
3 fatty acids in a triglyceride
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Proteins
Proteins account for 50% of dry mass of cells. Protein functions include structural support,
storage, transport, cellular communications, movement, and defense against foreign
substances.
Enzymes - act as a catalyst to speed up reactions
can perform their functions repeatedly, functioning as workers
enable processes of life
Polypeptides - polymers built from same set of 20 amino acids
each has a unique linear sequence of amino acids
a protein consists of one or more polypeptides
Peptide bonds - link amino acids
Disulfide bonds - reinforce structure of protein
In antibodies Holo protein in complete antibody
Amino Acids - organic molecules
carboxyl and amino groups
differ in properties due to differing side chains, called R chains
must recognize non-polar, polar, and electrically charged amino acids
Levels of Protein Structure
Structure of a protein determines its function
• Primary structure -sequence of amino acids
-precise primary structure is determined by inherited genetic information
-order of amino acids is important; like the lettering in a long word
• Secondary structure-coils and folds in the polypeptide
-result of hydrogen bonds between repeating constituents of polypeptide backbone
-alpha helix
-beta pleated sheets
• Tertiary structure -three dimensional structure
-determined by interactions between R groups
- interactions include hydrogen bonds, ionic bonds, hydrophobic interactions, and van der
Waals interactions
-Strong covalent bonds called disulfide bridges may reinforce the protein's structure
• Quaternary structure -multiple polypeptides
results when two or more polypeptide chains form one macromolecule
eg) hemoglobin
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What Determines Protein Structure?
primary structure
physical and chemical environment
pH, salt concentration, temperature, and other factors
Denaturation - loss of a protein's native structure
denatured protein in biologically inactive
protein unravels
eg) boiling an egg
eg) perming hair
Protein Folding
- difficult to predict a protein's structure from its primary structure
- most proteins go through several states on their way to a stable structure
- Chaperonins - protein molecules that assist proper folding of other proteins
EXAMPLE:
Hemoglobin is a globular protein consisting of four polypeptides:
two alpha and two beta chains
both a "a" and "B" subunits consist primarily of alpha helical secondary structure
each subunit has a non-polypeptide: heme contains an iron atom to bind to oxygen
Sickle-Cell Disease: A Change in Primary Structure
• slight change in primary structure can affect a protein's structure and ability to function
Sickle-cell disease, an inherited blood disorder, results from a single amino acid
substitution
in the protein hemoglobin
Biotechnology
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We must know the sequence of DNA to find out the exons and codons. If we know the
sequence, we can synthesize proteins. Insulin is a protein that is produced commercially
through biotechnology.
Polymerization template
DNA polymerase reads template and inserts nucleotides. Nucleotides are labeled with
fluorescent groups. Dye is added to the nucleotide that machines can detect to determine
the sequence.
Adenine is dyed red. Every time red appears, we know it is adenine in the sequence.
Cloning
Take pieces of DNA and copy them many times over.
Bacteria use enzymes called restriction endonucleases to isolate DNA that can be copied.
DNA double strand
Antiparallel
Polar
Protein Production
DNA sequence required
Ribosomes make proteins with mRNA, 20 ammino acids, tRNA to encode for the amino
acids
We can use other organisms to make proteins for the lab
Bacteria have ribosomes and tRNA and can produce proteins.
Pig can express the green fluorescent protein from the jellyfish.
PCR
polymerase chain reaction
similar to replication
SEE TEXTBOOK!!!
Amplify DNA
Start with one molecule and can change it to many.
All you need is one copy of the genome
Ch 13 Meiosis and Sexual Life Cycles
Inheritance of Genes and Reproduction
Genes are the units of heredity
Each gene has a specific location called a locus on a certain chromosome
DNA is packaged into chromosomes
Genes are passed to the next generation through reproductive cells called gametes (sperm
and eggs)
Asexual - one parent produces genetically identical offspring by mitosis
- clones are produced
other organisms can be cloned by this technique
Epigenetics (epi=outside of genetics) modifying the genome
Sexual Reproduction - two parents give rise to offspring that have unique
Bio 1010
- combinations of genes inherited from the two parents
Karyotype - an ordered display of the pairs of chromosomes from a cell
Homologous chromosomes - homologs - A pair of chromosomes of the same length,
centromere position, and staining pattern that possess genes for the same characters at
corresponding loci (carry genes controlling the same inherited characters).
Sex Chromosomes
females have a homologous pair of XX
males have one X and one Y chromosome
The 22 pairs of chromosomes that do not determine sex are called autosomes
diploid cell
A cell containing two sets of chromosomes one set inherited from each parent
found in somatic cells
humans have diploid number of 46 (2n)
haploid cell
A cell containing only one set of chromosomes (n=23)
found in gametes
Gametes are produced by meiosis
each set of 23 consist of 22 autosomes and a single sex chromosome
In an unfertilized egg - ovum - the sex chromosome is X
In a sperm cell, the sex chromosome can be either X or Y
In a cell in which DNA synthesis has occurred, each chromosome is replicated
Each replicated chromosome consists of two identical sister chromatids
Fertilization - union of two haploid gametes
Zygote - diploid with one set of chromosomes from each parent
Stages of Meiosis
Meiosis I - homologous chromosomes separate
- haploid daughter cells with replicated chromosomes,
called reductional division
Three events are unique to meiosis. All occur in meiosis I
Meiosis II - sister chromatids separate
- four haploid cells result with unreplicated chromosomes,
called equational division
- very similar to mitosis
Meiosis I
Prophase I
The sister chromatids are genetically identical and joined at the centromere
The single centrosome replicates, forming two centrosomes
preceded by interphase
very long
chromosomes begin to condense
synapsis
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homologous chromosomes loosely pair up, aligned gene by gene
crossing over
nonsister chromatids exchange DNA segments
tetrad
each pair of chromosomes forms a group of four chromatids
chiasmata
tetrads usually have X-shaped regions where crossing over occurred
Mitosis vs. Meiosis
Mitosis - conserves the number of chromosome sets
- producing cells that are genetically identical to parent cell
Meoisis
reduces the number of chromosomes sets from two (diploid) to
one (haploid), producing cells that differ genetically from each other and from the parent
cell
*see figure 13.9 on page 256
Three events are unique to meiosis, and all three occur in meiosis l:
-Synapsis and crossing over in prophase I: Homologous chromosomes physically
connect
and exchange genetic information
-At the metaphase plate, there are paired homologous chromosomes (tetrads), instead of
individual replicated chromosomes
-At anaphase I, it is homologous chromosomes, instead of sister chromatids, that separate
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Evolution
Alleles are the different versions of genes
Reshuffling alleles during sexual reproduction (division, crossing over) produces genetic
variation in offspring
Behaviour of chromosomes in meiosis and fertilization is responsible for most variation
Origins of Genetic Variation Among Offspring
• The behavior of chromosomes during meiosis and fertilization is responsible for most of
the variation that arises in each generation
• Three mechanisms contribute to genetic variation:
Independent assortment of chromosomes
Crossing over
Random fertilization
Independent Assortment of Chromosomes
• Homologous pairs of chromosomes orient randomly at metaphase I of meiosis
• In independent assortment, each pair of chromosomes sorts maternal and paternal
homologues into daughter cells independently of the other pairs
Each separation event is independent of another
Crossing Over
• Crossing over produces recombinant chromosomes, which combine genes inherited from
each parent
• In crossing over, homologous portions of two nonsister chromatids trade places
• Crossing over contributes to genetic variation by combining DNA from two parents into a
single chromosome
Random Fertilization
• Random fertilization adds to genetic variation because any sperm can fuse with any ovum
(unfertilized egg)
• Crossing over adds even more variation Each zygote has a unique genetic identity
Unique individuals in a population
- selection Evolution
You should now be able to:
1. Distinguish between the following terms: somatic cell and gamete; autosome and sex
chromosomes; haploid and diploid
2. Describe the events that characterize each phase of meiosis
3. Describe three events that occur during meiosis I but not mitosis
4. Name and explain the three events that contribute to genetic variation in sexually
reproducing organisms
Ch. 14 Mendel and Genes
The theory of evolution and the molecule of DNA
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Observations:
-Individuals in a population vary in their heritable characteristics.
-Organisms produce more offspring than the environment can support.
Inferences:
-Individuals that are well suited to their environment tend to leave more offspring than
other individuals
-Over time, favorable traits accumulate in the population.
Mendelian Genetics:
Which genetic principles account for the passing of traits from parents to offspring?
The "blending" hypothesis - genetic material from two parents blends together
The "particulate" hypothesis - parents pass on discrete heritable units (genes)
Mendel documented a particulate mechanism through his experiments and discovered the
basic principles of heredity by breeding garden peas
Advantages of pea plants for genetic study:
-Varieties with distinct heritable features, or characters (eg flower color);
character variants (purple or white flowers) are called traits
-Mating of plants can be controlled
-Each pea plant has sperm- and egg-producing organs (stamens and carpels)
-Cross-pollination (fertilization between different plants) can be achieved by dusting one
plant with pollen from another
Mendel's Crosses
Mendel chose to track only those characters that varied in an either-or manner
P generation
• used varieties that were true-breeding
(plants that produce offspring of the same variety when they self-pollinate)
F1 generation
• When Mendel crossed contrasting, true- breeding white and purple flowered pea plants,
all of the F1 hybrids were purple
• Hybridization - the mating or crossing of two true-breeding varieties
F2 generation
• When Mendel crossed the F1 hybrids, many of the F2 plants had purple flowers, but some
had white
Results
• Mendel discovered a ratio of about three to one, purple to white flowers, in the F2
generation
• Mendel reasoned that only the purple flower factor was affecting flower color in the F1
hybrids
• Mendel called the purple flower color a dominant trait and the white flower color a
recessive trait
Bio 1010
• What Mendel called a "heritable factor" is what we now call a gene
Mendel's Model
•Mendel developed a hypothesis to explain the 3:1 inheritance pattern he observed in F2
offspring
• Four related concepts make up this model
• These concepts can be related to what we now know about genes and chromosomes
The first concept
alternative versions of genes account for variations in inherited characters
• For example, the gene for flower color in pea plants exists in two versions, one for purple
flowers and the other for white flowers
• These alternative versions of a gene are now called alleles
• Each gene resides at a specific locus on a specific chromosome
The second concept
for each character an organism inherits two alleles, one from each parent
identical - true breeding
• Mendel made this deduction without knowing about the role of chromosomes
• The two alleles at a locus on a chromosome may be identical, as in the true-breeding
plants of Mendel's P generation
• Alternatively, the two alleles at a locus may differ, as in the F1 hybrids
The third concept
if the two alleles at a locus differ, then one (the dominant allele) determines the organism's
appearance, and the other (the recessive allele) has no noticeable effect
• In the flower-color example, the F1 plants had purple flowers because the allele for that
trait is dominant
What makes an allele dominant?
Protein structure
Active enzymes encode for colour/ dye
*look up word: streptomycin*
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The fourth concept
Law of Segregation
two alleles for a heritable character separate during gamete formation and
end up in different gametes
• Thus, an egg or a sperm gets only one of the two alleles that are present in the somatic
cells of an organism
Mendel's segregation model accounts for the 3:1 ratio he observed in the F2
generation of his numerous crosses
• This segregation of alleles corresponds to meiosis
• The possible combinations of sperm and egg can be shown using a Punnett square, a
diagram for predicting the results of a genetic cross between individuals of known genetic
makeup
• A capital letter represents a dominant allele, and a lowercase letter represents a
recessive
allele
Vocabulary
Mendel called "genes" as "factors"
Used 7 different traits (see table 14.1)
Alleles - different sequence of DNA
- alternate forms of genes
Traits - arise from different genes
Locus: site on the gene where two alleles are located
Homozygous - an organism with two identical alleles
true breeding
Heterozygous - an organism has two different alleles for a gene is said to be
heterozygous for the gene controlling that character
Phenotype - trait that is physical appearance
Genotype - genetic makeup
The Relation Between Dominance and Phenotype
• dominant allele does not subdue a recessive allele; alleles don't interact
Alleles are simply variations in a gene's nucleotide sequence
For any character, dominance/recessiveness relationships of alleles depend on the level at
which we examine the phenotype
Testcross
How can we tell the genotype of an individual with the dominant phenotype?
Such an individual must have one dominant allele, but the individual could be either
homozygous dominant or heterozygous
Carry out a testcross: breed the individual with a homozygous recessive individual
If any offspring display the recessive phenotype, the mystery parent must have been
heterozygous
The Law of Independent Assortment
• Mendel derived the law of segregation by following a single character
• The F1 offspring produced in this cross were monohybrids, individuals that are
heterozygous for one character
• A cross between such heterozygotes is called a monohybrid cross
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• Mendel identified his second law of inheritance by following two characters at the same
time
• Crossing two true-breeding parents differing in two characters produces dihybrids in the
F1 generation, heterozygous for both characters
• A dihybrid cross, a cross between F1 dihybrids, can determine whether two characters are
transmitted to offspring as a package or independently
• Using a dihybrid cross, Mendel developed the law of independent assortment
• Strictly speaking, this law applies only to genes on different, nonhomologous
chromosomes
Law of Independent Assortment
- each pair of alleles segregates independently of each other pair of alleles
during gamete formation
Mendelian Genetics reflect Probability
Exceptions:
Extending Mendelian Genetics for a Single Gene
Inheritance of characters
• Inheritance of characters by a single gene may deviate from simple Mendelian patterns in
the following situations:
-When alleles are not completely dominant or recessive
- When a gene has more than two alleles
- When a gene produces multiple phenotype
*disorders
Human Traits follow Mendelian Genetics
Recessively Inherited Disorders
• Many genetic disorders are inherited in a recessive manner
• Many diseases, such as heart disease and cancer, have both genetic and environmental
components
• Little is understood about the genetic contribution to most multifactorial diseases
You should now be able to:
1. Describe Lamarck's theories, and explain why they have been rejected
2.Explain what Darwin meant by "descent with modification"
3.List and explain Darwin's four observations and two inferences.
4.Explain why an individual organism cannot evolve
5.Describe at least four lines of evidence for evolution by natural selection (although we
stress the scientific view of evolution, we do not mean that socially, we should not
necessarily have survival of the fittest)
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1. Define the following terms: true breeding, hybridization, monohybrid cross, P generation,
F1 generation, F2 generation
2. Distinguish between the following pairs of terms: dominant and recessive; heterozygous
and homozygous; genotype and phenotype
3. Use a Punnett square to predict the results of a cross and to state the phenotypic and
genotypic ratios of the F2 generation
Ch 15 Chromosomes
Overview: Locating Genes Along Chromosomes
• Mendel's "hereditary factors" were genes, though this wasn't known at the time
• Today we can show that genes are located on chromosomes
• The location of a particular gene can be seen by tagging isolated chromosomes with a
fluorescent dye that highlights the gene
• We can sequence genes
Mendelian inheritance has its physical basis in the behavior of chromosomes
• Mitosis and meiosis were first described in the late 1800s
chromosome theory of inheritance
A basic principle in biology stating that genes are located on chromosomes and that the
behavior of chromosomes during meiosis accounts for inheritance patterns.
- Mendelian genes have specific loci (positions) on chromosomes
- Chromosomes undergo segregation and independent assortment
The behavior of chromosomes during meiosis was said to account for Mendel's laws of
segregation and independent assortment
Morgan's Experimental Evidence: Scientific Inquiry
• The first solid evidence associating a specific gene with a specific chromosome came from
Thomas Hunt Morgan, an embryologist
• Morgan's experiments with fruit flies provided convincing evidence that chromosomes are
the location of Mendel's heritable factors
Fruit flies are a model organism for genetic studies:
They have many offspring
A
D
rosophila
XW+
Y
generation can be bred every two weeks
They have only four pairs of chromosomes
Morgan noted wild type, or normal, phenotypes that were common in the fly populations.
Traits alternative to the wild type are called mutant phenotypes
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W+
red X
Wt - white X1
39
XX red
X1X red
(XW+ and XWt-)
XY red
X1Y white
Correlating Behavior of a Gene's Alleles with Behavior of a Chromosome Pair
In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with
red eyes (wild type)
Fruit Flies
The F1 generation all had red eyes
The F2 generation showed the 3:1 red:white eye ratio,
only males had white
the white-eyed mutant allele must be located on the X chromosome
Morgan's finding supported the chromosome theory of inheritance
Sex-linked genes exhibit unique patterns of inheritance
In humans and some other animals, there is a chromosomal basis of sex determination
The Chromosomal Basis of Sex
• In humans and other mammals, there are two varieties of sex chromosomes: a larger X
chromosome and a smaller Y chromosome
• Only the ends of the Y chromosome have regions that are homologous with the X
chromosome
• The SRY gene, (testes determining factor) on the Y chromosome codes for the
development of testes
Inheritance of Sex-Linked Genes
• The sex chromosomes have genes for many characters unrelated to sex
• A gene located on either sex chromosome is called a sex-linked gene
• In humans, sex-linked usually refers to a gene on the larger X chromosome
• Sex-linked genes follow specific patterns of inheritance
• For a recessive sex-linked trait to be expressed
- A female needs two copies of the allele A male needs only one copy of the allele
• Sex-linkedrecessivedisordersaremuchmore common in males than in females
Examples of sex-linked phenotypes
Color blindness
Duchenne muscular dystrophy
Hemophilia
X Inactivation in Female Mammals (epigenetics)
• In mammalian females, one of the two X chromosomes in each cell is randomly inactivated
• This occurs during embryonic development
• The inactive X condenses into a Barr body
• If a female is heterozygous for a particular gene located on the X chromosome, she will be
a mosaic for that character
Barr body
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A dense object lying along the inside of the nuclear envelope in cells of female mammals,
representing a highly condensed, inactivated X chromosome.
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Non-independent Assortment
Occurs with linked genes - genes occur on same chromosome
Some genes do not segregate independently
• Genes located on the same chromosome that tend to be inherited together are called
linked genes
• Each chromosome has hundreds or thousands of genes
Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry
• A genetic map, an ordered list of the genetic loci along a particular chromosome
• the farther apart two genes are, the higher the probability that a crossover will occur
between them and therefore the higher the recombination frequency
Genetic Disorders
Abnormal Chromosome Number
Nondisjunction - An error in meiosis or mitosis in which members of a pair of homologous
chromosomes or a pair of sister chromatids fail to separate properly from each other.
• A linkage map is a genetic map of a chromosome based on recombination frequencies
• linkage maps techniques are being made redundant
• Today, genomes are sequenced, so we know the exact distance, in base pairs, between
genes.
Alterations of chromosome number or structure cause some genetic disorders
Large-scale chromosomal alterations often cause a variety of developmental disorders
Changes in chromosome number
Changes in chromosome structure
Abnormal Chromosome Number
• In nondisjunction, pairs of homologous chromosomes do not separate normally during
meiosis
• As a result, one gamete receives two of the same type of chromosome, and another gamete
receives no copy
Polyploidy
• is a condition in which an organism has more than two complete sets of chromosomes
- Triploidy (3n) is three sets of chromosomes
- Tetraploidy (4n) is four sets of chromosomes
• Polyploidy is common in plants, but not animals
• Polyploids are more normal in appearance than aneuploids
Alterations of Chromosome Structure
Breakage of a chromosome can lead to changes in chromosome structure:
- Deletion removes a chromosomal segment
- Duplication repeats a segment
- Inversion reverses a segment within a chromosome
- Translocation moves a segment from one chromosome to another
Human Disorders Due to Chromosomal Alterations
• Alterations of chromosome number and structure are associated with some serious
disorders
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• Down syndrome is an aneuploid condition that results from three copies of chromosome
21
• It affects about one out of every 700 children born in the United States
Genome Facts
The human genome is composed of 3.2 billion base pairs
Distributed in 23 chromosomes (technically 24 chromosomes)
Each chromosome contains one molecule of DNA and associated proteins Each cell
contains
2 copies of each chromosome (one from each parent)
46 chromosomes, 22 pairs common and 1 pair either xx or xy 46 molecules of DNA
Certain cancers, such as chronic myelogenous leukemia (CML), are caused by
translocations
of chromosomes
Genomic Imprinting
• Some modifications of DNA occur naturally
• For a few mammalian traits, the phenotype depends on which parent passed along the
alleles for those traits - epigenetics
Epigenetics
Genomic imprinting is the result of the methylation (addition of - CH3) of DNA
Genomic imprinting is thought to affect only a small fraction of mammalian genes
Most imprinted genes are critical for embryonic development
The Structures Relationships
-adenine and guanine
-uracil and thymine
-explanation for base pairing
-chemotherapy
You should now be able to:
1. Explain the chromosomal theory of inheritance and its discovery
2. Explain why sex-linked diseases are more common in human males than females
3. Distinguish between sex-linked genes and linked genes
4. Explain how meiosis accounts for recombinant phenotypes
6. Explain how nondisjunction canl ead to aneuploidy
7. Define trisomy, triploidy, and polyploidy
8. Distinguish among deletions, duplications, inversions, and translocations
9. Explain genomic imprinting
Ch 16
The Molecular Basis of Inheritance
Deoxyribonucleic acid
Overview: Life's Operating Instructions
• In 1953, James Watson and Francis Crick proposed a structure of deoxyribonucleic acid, or
DNA
• Hereditary information is encoded in DNA and reproduced in all cells of the body
• This DNA program directs the development of biochemical, anatomical, physiological, and
(to some extent) behavioural traits
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The Search for the Genetic Material: Scientific Inquiry
Darwin - evolution
Mendel - heredity
Pasteur - end of spontaneous generation and microbiology
Morgan - chromosomes
- chromosomes are composed of proteins and DNA
Overview
To understand the function of DNA, we will look at the origins of molecular biology
Experimental Biology to answer questions about heredity
Structure-Function relationships of molecules
Profound impact upon our understanding of biology
Profound impact on society
DNA is the genetic material
• Early in the 20th century, the identification of the molecules of inheritance loomed as a
major challenge to biologists
• Identification is not enough in science, one needs to propose a mechanism
- how does it work?
An experiment to test the role of DNA and proteins in genetic transmission
• The discovery of the genetic role of DNA began with research by Frederick Griffith in 1928
• Griffith worked with two strains of a bacterium, one pathogenic and one harmless
see Griffith's experiment
Evidence That Viral DNA Can Program Cells
• More evidence for DNA as the genetic material came from studies of viruses that infect
bacteria
• Such viruses, called bacteriophages (or phages), are widely used in molecular genetics
research
• In 1952, Alfred Hershey and Martha Chase showed that DNA is the genetic material of a
phage known as T2
• They designed an experiment showing that only one of the two components of T2 (DNA or
protein) enters an E. coli cell during infection
• They concluded that the injected DNA of the phage provides the genetic information
Evidence was accumulating from experiments that DNA was the hereditary molecule.
But how? One needed a mechanism to explain it.
The discovery of the structure of DNA is one of best examples of a structure - function
relationship.
Johann Friedrich Miescher 1869 isolates DNA
(function unknown)
1950, Erwin Chargaff reported that there is an equal number of A and T bases, and an equal
number of G and C bases
Building a Structural Model of DNA: Scientific Inquiry
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• After most biologists became convinced that DNA was the genetic material, the challenge
was to determine how its structure accounts for its role
• Maurice Wilkins and Rosalind Franklin were using a technique called X-ray
crystallography to produce a picture of the DNA molecule
(a) Rosalind Franklin
(b) Franklin's X-ray diffraction photograph of DNA
• Franklin's X-ray crystallographic images of DNA enabled Watson to deduce that DNA was
helical
• The X-ray images also enabled Watson to deduce the width of the helix and the spacing of
the nitrogenous bases
• The width suggested that the DNA molecule was made up of two strands, forming a double
helix
Understand the Following:
The experimental evidence that led to the discovery of DNA The structure of DNA and how
it is related to the function of DNA The molecular basis of DNA replication Telomeres (page
318) Chromosome structure
Evidence was accumulating from experiments that DNA was the hereditary molecule. But
how? One needed a mechanism to explain it.
The discovery of the structure of DNA is one of best examples of a structure - function
relationship.
Many proteins work together in DNA replication and repair
• The relationship between structure and function is manifest in the double helix
• Watson and Crick noted that the specific base pairing suggested a possible copying
mechanism for genetic material
Features of the Watson and Crick model
It was coherent with biological facts Nucleic acids
Chargaff's rules Spacing of nucleotides
It suggested a mechanism for storing information It suggested a mechanism for diversity
from simplicity
Structure and function
Base pairing uses hydrogen bonds that creates specificity with low energy requirements
Base pairing suggested a possible copying mechanism for genetic material
Base order (sequence) suggests information
phosphate - ribose sequence does not contain information
base sequence can contain enormous amounts of information related to the
number of nucleotides that are used
Base Positions Possible outcomes
1
4
2
16
3
64
4
256
3,200,000,000 4 3,200,000,000
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DNA is used in two ways
- Storing information (archiving)
- Instructions to make proteins (translation)
•Since the two strands of DNA are complementary, each strand acts as a template for
building a new strand in replication
•the strands are relatively easily separated
•is a mechanism for making copies
Watson and Crick's semiconservative model of replication predicts that when a DNA
molecule is copied (replicated)...
each daughter molecule will have one old strand (derived or "conserved" from the parent
molecule) and one newly made strand
DNA is made in cells by a carefully regulated enzyme system
The copying of DNA is remarkable in its speed and accuracy
More than a dozen enzymes and other proteins participate in DNA replication
Molecular tool-kit to make DNA
Know their function and relate it to DNA synthesis
• Replication begins at special sites called origins of replication, where the two DNA strands
are separated, opening up a replication "bubble"
• A eukaryotic chromosome may have hundreds or even thousands of origins of replication
• Replication proceeds in both directions from each origin, until the entire molecule is
copied
Ch 15
You should now be able to:
1. Explain the chromosomal theory of inheritance and its discovery
2. Explain why sex-linked diseases are more common in human males than females
3. Distinguish between sex-linked genes and linked genes
4. Explain how meiosis accounts for recombinant phenotypes
6. Explain how nondisjunction canl ead to aneuploidy
7. Define trisomy, triploidy, and polyploidy
8. Distinguish among deletions, duplications, inversions, and translocations
9. Explain genomic imprinting
Ch 16
You should now be able to:
Ch 17
The theory of evolution and the molecule of DNA
DNA is used in two ways
- Storing information (archiving)
• replication and mitosis
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- Instructions to make polypeptides
• transcription and translation
Nutritional Mutants in Neurospora: Scientific Inquiry
• George Beadle and Edward Tatum used an excellent model system to answer a complex
biological question
- Do genes encode enzymes?
• They developed a one gene-one enzyme hypothesis, which states that each gene dictates
production of a specific enzyme
• George Beadle and Edward Tatum exposed bread mold to X-rays
• This created mutants that were unable to synthesize certain molecules
• X-rays are electromagnetic radiation (chpt 10) that can damage DNA at certain sites
• If DNA is damaged, then genes might be damaged, and proteins will not be made
• Cells use pathways in metabolism, signalling and cell cycle (Chpt 9, 11, 12)
The synthesis of Arginine from Ornithine via gene products (enzymes)
Conclusion:
Making the link between genes and proteins
• RNA is the intermediate between genes and the proteins
- RNA contain ribose instead of deoxyribose
- RNA use uracil nucleotides instead of thymidine nucleotides
Basic Principles of Transcription and Translation
• Transcription is the synthesis of RNA under the direction of DNA
• Transcription produces messenger RNA (mRNA)
• Translation is the synthesis of a polypeptide, which
occurs under the direction of mRNA
• Ribosomes are the sites of translation
Molecular Components of Transcription
• RNA synthesis differs from DNA synthesis
- substrates
- the entire genome is not transcribed, only specific genes, a type of regulation that requires
regulatory units
• Promoter - The DNA sequence to which RNA polymerase attaches
• Transcription unit - The stretch of DNA that is transcribed
• mRNA - messenger RNA, the RNA used in translation
• Transcription factors - proteins that mediate RNA polymerase binding to specific DNA
sequences
• TATA box - a DNA sequence that is required for initiating RNA synthesis
• Polyadenylation signal - a stretch of RNA where all the bases are adenines, at the end of an
RNA molecule a sequence that signals termination in eukaryotic mRNA
• RNA polymerase II - the enzyme the synthesizes mRNA
Elongation of the RNA Strand
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• As RNA polymerase moves along the DNA, it untwists the double helix, 10 to 20 bases at a
time
• Transcription progresses at a rate of 40 nucleotides per second in eukaryotes
• A gene can be transcribed simultaneously by several RNA polymerases
Eukaryotic cells modify RNA after transcription
• Enzymes in the eukaryotic nucleus modify pre- mRNA before the genetic messages are
dispatched to the cytoplasm
• During RNA processing, both ends of the primary transcript are usually altered
• Also, usually some interior parts of the molecule are cut out, and the other parts spliced
together
Enzymes in the eukaryotic nucleus modify pre-mRNA before the genetic messages are
dispatched to the cytoplasm
• Each end of a pre-mRNA molecule is modified in a particular way:
-
-A tail
• These modifications share several functions:
- They seem to facilitate the export of mRNA
- They protect mRNA from hydrolytic enzymes
- They help ribosomes attach t
Split Genes and RNA Splicing
• Most eukaryotic genes and their RNA transcripts have long noncoding stretches of
nucleotides that lie between coding regions
• These noncoding regions are called intervening sequences, or introns
• The other regions are called exons because they are eventually expressed, usually
translated into amino acid sequences
• RNA splicing removes introns and joins exons, creating an mRNA molecule with a
continuous coding sequence
In some cases, RNA splicing is carried out by spliceosomes
• Spliceosomes consist of a variety of proteins and several small nuclear ribonucleoproteins
(snRNPs) that recognize the splice sites
• In some cases, RNA splicing is carried out by spliceosomes
• Spliceosomes consist of a variety of proteins and several small nuclear ribonucleoproteins
(snRNPs) that recognize the splice sites
The Functional and Evolutionary Importance of Introns
• Some genes can encode more than one kind of polypeptide, depending on which segments
are treated as exons during RNA splicing
• Such variations are called alternative RNA splicing
• Because of alternative splicing, the number of different proteins an organism can produce
is much greater than its number of genes
• Some genes can encode more than one kind of polypeptide, depending on which segments
are treated as exons during RNA splicing
• Such variations are called alternative RNA splicing
• Because of alternative splicing, the number of different proteins an organism can produce
is much greater than its number of genes
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Ribozymes
• Ribozymes are catalytic RNA molecules that function as enzymes and can splice
RNA
• The discovery of ribozymes rendered obsolete the belief that all biological catalysts were
proteins
• Three properties of RNA enable it to function as an enzyme
- It can form a three-dimensional structure because of its ability to base pair with itself
- Some bases in RNA contain functional groups
- RNA may hydrogen-bond with other nucleic acid molecules
Transcription - review
• RNA is another type of nucleic acid with specific chemical properties
- uracil and 2' hydroxyl group - unstable
• Like DNA, RNA is synthesized in 5' to 3' direction
• RNA can be multi-copy; DNA is one or two copies
• RNA is single stranded; DNA is double stranded
• RNA can be edited, this expands the genome information
• RNA can have catalytic activity
The Genetic Code
• How are the instructions for assembling amino acids into proteins encoded into DNA?
• There are 20 amino acids, but there are only four nucleotide bases in DNA
• How many bases correspond to an amino acid?
Codons: Triplets of Bases
• The flow of information from gene to protein is based on a triplet code: a series of
nonoverlapping, three-nucleotide words
• These triplets are the smallest units of uniform length that can code for all the amino acids
• Example: ATG at a particular position on a DNA strand results in the amino acid
methionine
• RNA is the intermediate between genes and the proteins
- RNA contain ribose instead of deoxyribose
- RNA use uracil nucleotides instead of thymidine nucleotides
Cracking the Code
• All 64 codons were deciphered by the mid- 1960s
• Of the 64 triplets, 61 code for amino acids; 3 triplets are "stop" signals to end translation
• No codon specifies more than one amino acid
• Codons must be read in the correct reading frame (correct groupings) in order for the
specified polypeptide to be produced
Evolution of the Genetic Code
• The genetic code is nearly universal, shared by the simplest bacteria to the most complex
animals
• Genes can be transcribed and translated after being transplanted from one species to
another
Molecular Components of Translation
• A cell translates an mRNA message into protein with the help of transfer RNA (tRNA)
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• Molecules of tRNA :
- Each carries a specific amino acid on one end
- Each has an anticodon on the other end; the anticodon base-pairs with a complementary
codon on mRNA
- A tRNA molecule consists of a single RNA strand that is only about 80 nucleotides long
• Accurate translation requires two steps:
-First: a correct match between a tRNA and an amino acid, done by the enzyme aminoacyltRNA synthetase
- Second: a correct match between the tRNA anticodon and an 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
Ribosomes
• Ribosomes facilitate specific coupling of tRNA anticodons with mRNA codons in
protein
synthesis
• The two ribosomal subunits (large and small) are made of proteins and ribosomal RNA
(rRNA)
A ribosome has three binding sites for tRNA:
- The P site holds the tRNA that carries the growing polypeptide chain
- The A site holds the tRNA that carries the next amino acid to be added to the chain
- The E site is the exit site, where discharged tRNAs leave the ribosome
Building a Polypeptide
• The three stages of translation:
- Initiation
- Elongation
- Termination
• All three stages require protein "factors" that aid in the translation process
Ribosome Association and Initiation of Translation
• The initiation stage of translation brings together mRNA, a tRNA with the first amino acid,
and the two ribosomal subunits
• First, a small ribosomal subunit binds with mRNA and a special initiator tRNA
• Then the small subunit moves along the mRNA until it reaches the start codon (AUG)
• Proteins called initiation factors bring in the large subunit that completes the translation
initiation complex
Termination of Translation
• Termination occurs when a stop codon in the mRNA reaches the A site of the ribosome
• The A site accepts a protein called a release factor
• The release factor causes the addition of a water molecule instead of an amino acid
• This reaction releases the polypeptide, and the translation assembly then comes apart
Polyribosomes
• A number of ribosomes can translate a single mRNA simultaneously, forming a
polyribosome (or polysome)
• Polyribosomes enable a cell to make many copies of a polypeptide very quickly
Instructions to make polypeptides
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• transcription
• RNA processing
• translation
• Variation in DNA
Ch 18 - Regulation of Gene Expression
Differential Gene Expression
The cells in an organism are genetically identical
Differences between cell types result from differential gene expression, the expression of
different genes by cells with the same genome
Errors in gene expression can lead to diseases including cancer
Regulation of Bacterial Gene Expression
• Environmental conditions - Metabolism
• OPERON
- transcriptional unit that contains the promoter, the operator and a cluster of genes they
control
- single mRNA (coordinate control)
- Negative gene regulation - repressible and inducible operons
- Positive gene regulation
• There are two types of genes:
- Structural genes
- Regulatory genes
Tryptophan and Lactose models
E.coli - synthesizes the amino acid Tryptophan and Lactose models
Tryptophan
- Trp operon is usually on
Negative gene regulation
- Repressible operon
• Trp operon is switched off by Trp repressor
• Trp repressor is inactive by itself - needs
corepressor = Tryptophan
Inducible operon
• Lactose is used by E. coli as energy source
• Lac operon is usually off (no lactose)
• Lac repressor is ACTIVE by itself
• Lactose present: the inducer protein (allolactose) inactivates the repressor and turns on
transcription
• Trp and lac genes are both NEGATIVELY controlled
• In positive regulation the regulatory protein interacts DIRECTLY with the genome to turn
transcription on
Positive gene regulation
• Glucose and Lactose - E. coli prefers glucose as energy source
• Low glucose: the regulatory protein called Catabolic Activator Protein (CAP) is an
activator that binds to cAMP (accumulates when glucose is scarce) and attaches upstream of
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lac promoter - increases affinity of RNA polymerase II to the promoter - turns on
transcription
• High glucose: low cAMP - does not stimulate transcription
Lactose
Lac operon is usually off (no lactose)
Regulation of Eukaryotic Gene Expression
Eukaryotic gene transcription - the genome is the same
Chromatin modifications
Regulation of transcription initiation
RNA processing
Non coding RNA
RNA interference
Chromatin modification
• Histone acetylation - the attachment of acetyl groups to certain amino acids of histone
proteins. Acetyl groups are attached to positively charged lysines in histone tails.
• This process loosens chromatin structure, thereby promoting the initiation of
transcription
• Histonemethylation,Methylgroups (methylation) can condense chromatin
• Histonephosphorylation,phosphategroups next to a methylated amino acid can loosen
chromatin
DNA Methylation
• DNA methylation, the addition of methyl groups to certain bases in DNA, is associated with
reduced transcription in some species
• DNA methylation can cause long-term inactivation of genes
• In genomic imprinting, methylation regulates expression of either the maternal or
paternal alleles of certain genes at the start of development
• Although the chromatin modifications do not alter DNA sequence, they may be passed to
future generations of cells, which is called epigenetic inheritance
A bacterial cell can transcribe and translate at the same time
A eukaryotic cell needs a nuclear envelope because the mRNA is processed before it
leaves
the nucleus
Organization of a Typical Eukaryotic Gene
• Transcription factors: proteins that mediate the binding of RNA polymerase and initiation
of transcription (Transcription Initiation complex)
• Eukaryotic genes are regulated by control elements, segments of noncoding DNA that help
regulate transcription by binding certain proteins
• Control elements and the proteins they bind are critical to the precise regulation of gene
expression in different cell types
Enhancers and Specific Transcription Factors
• Proximal control elements are located close to the promoter
• Distal control elements, groups of which are called enhancers, may be far away from a
gene or even located in an intron
Combinatorial Control of Gene Activation
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A particular combination of control elements can activate transcription only when the
appropriate activator proteins are present
Mechanisms of Post-Transcriptional Regulation
• Transcription alone does not account for gene expression
• Regulatory mechanisms can operate at various stages after transcription
• Such mechanisms allow a cell to fine- tune gene expression rapidly in response to
environmental changes
RNA Processing
In alternative RNA splicing, different mRNA molecules are produced from the same primary
transcript, depending on which RNA segments are treated as exons and which as introns
mRNA Degradation
• mRNA molecules have specific life spans
• The mRNA life span is determined in part by sequences in the leader and trailer regions
What is in the human genome?
• Only a small fraction of DNA codes for proteins, rRNA, and tRNA
• A significant amount of the genome may be transcribed into noncoding RNAs
• Noncoding RNAs regulate gene expression at two points: mRNA translation and
chromatin
configuration
RNA interference
• RNAi is the phenomenon of inhibition of gene expression by RNA molecules
• miRNA and siRNA: small single stranded RNA - regulate gene expression
• They bind to complementary mRNA molecules
• miRNA-protein complex degrades the target mRNA or blocks its translation
• miRNA and siRNA are very similar and have similar functions - they are formed by a
different precursor
Ch 19 - Viruses
Read textbook alone
Concept 17.5: Point mutations can affect protein structure and function
• Mutations are changes in the genetic material of a cell or virus
• Point mutations are chemical changes in just one base pair of a gene
• The change of a single nucleotide in a DNA template strand can lead to the production of
an abnormal protein
Types of Point Mutations
• Point mutations within a gene can be divided into two general categories
- Base-pair substitutions
(substitute one of four bases)
- Base-pair insertions or deletions
Substiutions
• A base-pair substitution replaces one nucleotide and its partner with another pair of
nucleotides
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• Silent mutations have no effect on the amino acid produced by a codon because of
redundancy in the genetic code
• Missense mutations still code for an amino acid, but not necessarily the right amino acid
• Nonsense mutations change an amino acid codon into a stop codon, nearly always
leading
to a nonfunctional protein
Insertions and Deletions
• Insertions and deletions are additions or losses of nucleotide pairs in a gene
• These mutations often have a major effect on the resulting protein (more often than do
substitutions)
• Insertion or deletion of nucleotides may alter the reading frame, producing a frameshift
mutation
Mutagens
• Spontaneous mutations can occur during DNA replication, recombination, or repair
• Mutagens are physical or chemical agents that can cause mutations
Viruses as Human Pathogens
FLU VIRUS DEFINITION
Flu is due to the virus Influenza family Orthomyxoviruses Antisense RNA virus
3 types Influenza virus: A, B, C
Type A is the most pathogen for humans responsible of pandemic disease, host is wild
aquatic birds
Type B infects human, seals and furet. Less common than type A Type C infects human, dog
and pigs. Less common than A or B. Mild disease.
Influenza Virus type A
Influenza
•Highly contagious acute disease of the upper respiratory tract
•Transmitted by
•airborne droplets
•direct contact of nasal secretions or birds dropping,
•contact with contaminated surfaces
•Name of the disease through the word « influenza de freddo »
•Influence of the cold
Since 1510, 31 pandemics
•Asiatic (Russian) flu1889-1890 H2N2
•Spanish flu 1918-1920 H1N1
•Asian Flu 1957-1958 H2N2
•Hong Kong Flu 1968-1969 H3N2
•Swine flu 2009
H1N1
Influenza
Structure
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• The genetic material for influenza A (H1N1) is in the form of RNA
• Negative strand RNA
• Eight single strands RNA
• Each helical strand is protected by protein (nucleocapsid)
16 H and 9 N in birds in humans H1, H2, H3, N1, N2
Structure
• A matrix protein surrounds the eight strands of RNA and an envelope surrounds the
matrix protein.
• Sticking out of the envelope are two types of surface antigens: hemagglutinin (H) and
neuraminidase (N).
• H, N, give the name for the influenza subtype.
Function
• Hemagglutinin (spikes) recognize sialic acid on the surface of epithelial cells. It allows for
the attachment and penetration of the virus in the host cells.
• Neuraminidase is a sialidase assists the entry and the exit of the virion. Allows the
budding.
• Both enzymes are antigens.
Function
RNA antisense viruses:
• The negative strand RNA acts as the template to produce the complementary mRNA
strand. This strand will be used for protein synthesis.
• The final stage in replication, is to form an envelope.
• The virus pushes through the portion of the cell membrane where the neuraminidase
spikes are waiting, so that it surrounds the virus in a process called budding.
Influenza A Replication
Many strains of influenza?
• Antigenic variation: antigenic drift (minor) or antigenic shift (major). Chemical changes
occurs periodically in hemagglutinin and neuraminidase
• Antigenic drift is caused by minor mutations. These mutations cause the HA and the NA to
accumulate changes
• Antigenic shift is the result of a huge change in the virus structure. This can lead to
completely new Hemagglutinin and Neuraminidase.
• There are two ways for this to happen.
Many strains of Influenza
Influenza A infects
•Humans
•Birds main animal reservoirs
•Pigs intermediate host
The swine flu, is a combination of swine flu, avian flu, and the human flu. Combined in the
pig.
Many strains of influenza?
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Pigs can be infected by avian, swine and/or humans
Allowing an antigenic shift
DISEASE
•Severe Headache
•Muscle pain
•Chills
•Fever
•Sore throat
•Coughing
•Weakness
•And general discomfort
•May cause nausea and vomiting
INFLUENZA
•recover within one to two weeks without medical treatment.
•In the very young, the elderly, and those with other serious medical conditions, infection
can lead to severe complications, pneumonia and death.
•Infected people can be contagious 1 day before the symptoms, and 7 days after. •The virus
can survive many days on a surface •The virus is more stable in dry air and cold
temperature (5°C)
INFLUENZA
The vaccine in Canada:
ArepanrixTM H1N1 (AS03-adjuvanted H1N1 pandemic influenza vaccine) Glaxo Smith
Kline
The virus is inactivated with ultraviolet light And fixed with formaldehyde treatment
Medicine: Tamiflu and Relenza
•targets the neuraminidase spikes
•blocks the release of the virus
Two serious complications of influenza:
• Guillain-Barr syndrome (GBS) nerve damage, polio-like paralysis, and coma (1 to 2 case
for 1 million of vaccinated person, with 90% of recovery)
• Reye's syndrome (children with Flu or chicken pox who has received aspirin): fever rises,
and repeated, vomiting. Probably due to activity of the immune sytem
H1N1 and some numbers
2% of the infected people will be hospitalized Between 1 and 10 persons out of 10 000
infected persons will die of it
As of 3 December- 1,000,000 persons have been vaccinated in Alberta 57 persons have
died
from H1N1 infection
Chapter 22 - Darwin and Evolution
"Nothing in biology makes sense except in the light of evolution"
Theodosius Dobzhansky (1900-1975)
Evolution - The Overarching Theme of Biology
Theory of Evolution - principles on which evolution is based
Theory - principles upon which a subject is based
Bio 1010
not an hypothesis -a possible answer to a well formulated question
1859 Charles Darwin - The Origin of Species
focused on the great diversity of organisms
noted that current species are descendants of common ancestors
revolutionary ideas challenged traditional views
Evolution - descent with modification
The view that all organisms are related through descent from an ancestor
that lived in the remote past
both a pattern and a process
change over time
Taxonomy
Linnaeus: classify organisms
The fact that species can be classified shows that there are relationships
(Domain, Kingdom, Phylum, Class, Order, Genus, Species)
thought could acquire traits - was disproved
Fossils
Georges Cuvier lay groundwork for Darwin's ideas
Fossil - remains or traces of organisms from the past, usually found in
sedimentary rock, which appears in layers or strata
Paleontology - study of fossils
Cuvier speculated that each boundary between strata represents a
catastrophe, the idea of catastrophism
Lamarck' Hypothesis of Evolution
Inheritance of acquired characteristics
species evolve through use and disuse of body parts
disproved through observation
Natural Selection explains Adaptations
Darwin perceived adaptation to the environment and the origin of new
species as closely related processes
Theme: organisms interact with their environment
The Origin of Species
Darwin wrote essay but did not publish his theory until Wallace had come to similar
conclusions. Darwin published his work, and as he expected, social uproar ensued.
Darwin developed two main ideas:
Descent with modification explains life's unity and diversity
Natural selection is a cause of adaptive evolution
In the Darwinian view, the history of life is like a tree
branches represent life's diversity
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observations of different living species, and fossils
Artificial Selection - humans have modified other species by selecting and breeding
individuals with desired traits
Four Observations of Nature and Two Inferences
Observations:
Members of a population often vary greatly in their traits
Traits are inherited from parents to offspring
All species are capable of producing more offspring than the environment can support
Owing to lack of food or other resources, many of these offspring do not survive
Inferences:
Individuals that are well suited to their environment tend to leave more offspring than
other individuals
Over time, favorable traits accumulate in the population.
Two examples provide evidence for natural selection:
The effect of differential predation on guppy populations
The evolution of drug-resistant HIV (antibiotic resistance)
Natural Selection:
can only increase or decrease heritable traits in a population
does not create traits - Lamarck was wrong
selects for traits already present in the population
The local environment determines which traits will be selected for or selected against in
any specific population
Evolutionary Tree
Tree of life can explain homologies
hypotheses about the relationships among different groups
Can be made using different types of data, for example, anatomical and DNA sequence data
You should now be able to:
1.
Describe Lamarck's theories, and explain why they have been rejected
2.
Explain what Darwin meant by "descent with modification"
3.
List and explain Darwin's four observations and two inferences.
4.
Explain why an individual organism cannot evolve
5.
Describe at least four lines of evidence for evolution by natural selection (although
we stress the scientific view of evolution, we do not mean that socially, we should not
necessarily have survival of the fittest)
Monday December 7, 2009
Chapter 17 - Completing the analysis of Evolution and DNA
Chapter 18 - Gene Regulation
Chapter 19 - Independent Review of viruses
Chapter 20 - Biotechnology and Overview of Biology
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Clicker Question
A bacterium is infected with a bacteriophage that has T2 protein coat and T4 DNA
The new phage will have:
T4 protein and T4 DNA
because DNA makes RNA makes protein
Chapter 18
If the genome is the same, why aren't all cells the same?
Each body part consists of specialized cells
Eukaryotic gene transcription
histone modifications
regulation of transcription initiation
RNA processing
Non coding RNA
RNA interference
Differential Gene Expression
The cells in an organism are genetically identical
Differences between cell types result from differential gene expression, the expression of
different genes by cells with the same genome
Errors in gene expression can lead to diseases including cancer
Overview: Gene expression is regulated
Prokaryotes and eukaryotes alter gene expression in response to their environment
In multicellular eukaryotes, gene expression regulates development and is responsible for
differences in cell types
In multicellular organisms gene expression is essential for cell specialization
*know steps in figure 18.6
gene - to - protein
The steps from genes to proteins can be regulated
The regulation steps that are used differs between cell types
Chromatin Modification
Chromatin is DNA and protein
Chromatin can be modified by changes in histones
• Histone acetylation, Acetyl groups are attached to positively charged lysines in histone
tails
• This process loosens chromatin structure, thereby promoting the initiation of
transcription
• Histone methylation, Methyl groups (methylation) can condense chromatin
• Histone phosphorylation, phosphate groups next to a methylated amino acid can loosen
chromatin
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DNA Methylation
Compare to histone (protein) methylation
• DNA methylation, the addition of methyl groups to certain bases in DNA, is
associated with reduced transcription in some species
• DNA methylation can cause long-term inactivation of genes
• In genomic imprinting, methylation regulates expression of either the maternal or
paternal alleles of certain genes at the start of development
• Although the chromatin modifications do not alter DNA sequence, they may be passed to
future generations of cells, which is called epigenetic inheritance
Organization of a Typical Eukaryotic Gene
• Eukaryotic genes are regulated by control elements, segments of noncoding DNA that help
regulate transcription by binding certain proteins
• Control elements and the proteins they bind are critical to the precise regulation of gene
expression in different cell types
enhancer - A segment of eukaryotic DNA containing multiple control elements, usually
located far from the gene whose transcription it regulates.
Enhancers and Specific Transcription Factors
• Proximal control elements are located close to the promoter
• Distal control elements, groups of which are called enhancers, may be far away from a
gene or even located in an intron
Combinatorial Control of Gene Activation
• A particular combination of control elements can activate transcription only when the
appropriate activator proteins are present
Mechanisms of Post-Transcriptional Regulation
• Transcription alone does not account for gene expression
• Regulatory mechanisms can operate at various stages after transcription
• Such mechanisms allow a cell to fine-tune gene expression rapidly in response to
environmental changes
RNA Processing
In alternative RNA splicing, different mRNA molecules are produced from the same primary
transcript, depending on which RNA segments are treated as exons and which as introns
mRNA Degradation
• mRNA molecules have specific life spans
• The mRNA life span is determined in part by sequences in the leader and trailer regions
What is in the human genome?
Only a small fraction of DNA codes for proteins, rRNA, and tRNA A significant amount of the
genome may be transcribed into noncoding RNAs
Noncoding RNAs regulate gene expression at two points: mRNA translation and chromatin
configuration
Recruitment of activators available in cell determine what genes will be expressed
Liver cell has access to different proteins in cell than Optic cell
Bio 1010
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Clicker Question
The part of the gene that ultimately encodes for proteins:
Exon encodes for amino acids
All organisms are the same
DNA - RNA - Proteins
Carbohydrates
Lipids
Proteins
Cell walls
Cell membranes
Organelles
Respiration
Protein
Synthesis
DNA
All organisms are different
Structural differences
Genomic differences
What makes organisms different from each other?
Identical
Individuals Species Orders Phyla
Different
Kingdoms Domains
If genomes were identical, then natural selection would not be possible Natural selection
selects differences
Differences of inheritable characteristics - genes - DNA
DNA
Evolution leads us to predict that DNA is different in different species and in different
individuals
- number of base pairs
- sequence of base pairs
- number of genome copies
DNA
What has led to differences in DNA between organisms?
- the DNA Biochemical pathways are not perfect
• DNA replication
• DNA transcription
• RNA translation
• Chromosome organization
• Mutation
DNA
What would happen if these biochemical events were perfect ?
Bio 1010
(zero error)?
- in an environment that never changes
- in an environment that changes
DNA replication
DNA transcription
RNA translation
Chromosome organization
Mutation
we will look closely at mutations
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