unit 04 population dynamics hiv and humans. building complexity from a single cell to a...
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Unit 04Population Dynamics
HIV and humans
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Building complexityFrom a single cell to a
population…
Single Cells
Population of viruses
Population of humans
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Single Cells
• How matter flows from cells through other cells
• How energy flows from the sun through plant and animal cells
• How cells respond to changes in their environment and reproduce
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Genomics and Proteomics– Genomics is the science of studying whole
genomes.
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Proteomics– Success in genomics has given rise to
proteomics,• The systematic study of the full set of
proteins found in organisms.
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What is a Population?
“A group of interacting individuals belonging to one species and
living in the same geographic area at the same time.”
Population of viruses in a single person at the same time
Population of humans in the same area at the same time
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Population Dynamics
• How do we study populations? – How do they grow?– How can we describe them?
• How do populations respond to the environment?
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HIV/AIDS
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HIV Disease progression
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Animal Viruses
– Viruses that infect animals are common causes of disease.
– From Medical Virology 4th Ed. By White and Fenner
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– The reproductive cycle of an enveloped virus
Simplified Viral Reproductive Cycle
Influenza virus
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HIV, the AIDS Virus– HIV is a
retrovirus.• A retrovirus is
an RNA virus that reproduces by means of a DNA molecule.
• It copies its RNA to DNA using reverse transcriptase
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– How HIV reproduces inside a CD4 + T lymphocyte (T cell)
Integrase
Protease
Glycoproteins gp120, gp41
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– AIDS is• Acquired immune deficiency syndrome.• The disease caused by HIV infection.• Treated with many classes of drugs:
– Reverse transcriptase inhibitors (AZT, ddC,…)– Protease inhibitors– Integrase inhibitors– Fusion inhibitors
http://www.youtube.com/watch?v=RO8MP3wMvqg
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HIV drug resistance:How does this happen?
2537 patients with HIV in the UK from 1996-2003.None had received anti-retrovirals before they joined the study.They were then placed on combination anti-retroviral therapy.
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HIV drug resistanceInitial ideas
• What would the genomes of a population of HIV viruses look like at each of the following time points:
• Time 0 – before anti-HIV drug is taken
• Time 1 – when the anti-HIV drug is taken
• Time 2 – some time later while the anti-HIV drug is still being taken.
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The Darwinian View of Life
The evolutionary view of life came into focus in 1859 when Charles Darwin published The Origin of Species.
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– Darwin’s book developed two main points:
• Descent with modification
• Natural selection
EVOLUTION
The Mechanism of EVOLUTION
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Natural Selection
– Darwin was struck by the diversity of animals on the Galápagos Islands.
– He thought of adaptation to the environment and
the origin of new species as closely related
processes.•As populations separated by a geographic barrier
adapted to local environments, they became separate
species.
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–Fourteen species of Galápagos finches have beak
shapes adapted to suit their environments.
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Darwin’s Inescapable Conclusion
– Fact 1: Potential for overproduction and competition for existence
– Fact 2: Individual variation
– The inescapable conclusion: Unequal reproductive successUnequal reproductive success
• Darwin called this process natural selection.• The result of natural selection is adaptation.
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Observing Artificial SelectionArtificial selection is the selective breeding of domesticated plants and animals by humans.
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Observing Natural Selection– There are many examples of natural selection
in action.• The development of antibiotic-resistant bacteria is
one.
Tuberculosis - MDR-TB - XDR-TB
Staphylcoccus aureus (staph) - CA-MRSA
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Darwin’s Inescapable Conclusion
– Fact 1: Potential for overproduction
and competition for existence
– Fact 2: Individual variation
– The inescapable conclusion:
Unequal reproductive successUnequal reproductive success• Darwin called this process natural selection.
• The result of natural selection is evolution when a population has adapted to its environment.
Evidence for HIV?
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How do we study overproduction and struggle
for existence?Look to Ecology
– Ecology• Is the scientific study of the interactions
between organisms and their environments.
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A Hierarchy of Interactions
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Population Growth Models
– Two models, the exponential growth model and the logistic growth model, will help us understand population growth.
– The growth rate• Is the change in population size over time
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The Exponential Growth Model: The Ideal of an Unlimited
Environment
– The exponential growth model• Describes the rate of expansion of a population
under ideal, unregulated conditions.– Enough food and resources– Waste is washed or taken away or not significant
Copyright © 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings
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Figure 18.17
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The Logistic Growth Model: The Reality of a Limited Environment
– In nature, a population may grow exponentially for a while, but eventually one or more environmental factors will limit its growth.
– Population-limiting factors restrict population growth.
Copyright © 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings
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– A comparison of the logistic growth model and the exponential growth model
–Carrying capacity•Is the number of individuals in a population that the environment can just maintain with no net increase or decrease.
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HIV Disease progression:Modified Logistic Growth Model
HIV can reproduce over a billion times a day.It is in a constant struggle for existence
with the immune system
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HIV drug resistance:How does this happen?
2537 patients with HIV in the UK from 1996-2003.None had received anti-retrovirals before they joined the study.They were then placed on combination anti-retroviral therapy.
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Darwin’s Inescapable Conclusion
– Fact 1: Potential for overproduction and competition for existence
– Fact 2: Individual variation
– The inescapable conclusion: Unequal reproductive successUnequal reproductive success
• Darwin called this process natural selection.• The result of natural selection is evolution when a
population has adapted to its environment.
Evidence for HIV?
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Random Mutations in the genome are the basis of
individual variation• Base substitution
– Silent mutation– Missense mutation– Nonsense mutation
• Insertion or deletion– Reading frame shift
• They occur at random by – Errors in DNA replication by enzymes– Exposure to mutagens (UV, chemicals, etc…)
• Mutations can be beneficial, harmless, or harmful
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– In 2003, the Food and Drug Administration
• Approved the drug gefinitib for the treatment of lung cancer.
• Gefinitib blocks signaling from a growth factor receptor (a receptor that signals the cell to grow and divide!) found in abundance on some lung cancer cells.
– Unfortunately, gefinitib is ineffective for many patients.
Copyright © 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings
An Example of Mutations that have an effect on drug response
in humans.
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– A 2004 study found that genetic differences among patients affected their response to the drug,
• Pre-existing individual variation
in a population of
humans affects their
ability to respond to
the drug.
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Figure 10.1
How does the anti-HIV drug AZT work?
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How do mutations cause drug resistance?
• http://www.cabm.rutgers.edu/~kalyan/RT_imgs/index.html
– Dr. Kalyan Das at Rutgers University
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How do mutations in the genome cause resistance?
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How do mutations in the genome cause resistance?
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Time 0:Overproduction and pre-existing individual variationcaused by random mutations
Natural Selection at work
Time 2:Populationhas evolved
Time 1:Struggle for existence:EnvironmentalSelection
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HIV drug resistance! How??
1. Large amount of offspring• HIV replicates over a billion times a day
2. Reverse transcriptase (RT) is error-prone!• About 50% of HIV DNA transcripts made by RT
contain at least one mistake (mutation) at random.
3. Random mutation is heritable
4. Mutants are better able to reproduce in
selective environment
5. Population adapts to change in environment,
resulting in a different population = evolution
Overproduction
HeritableIndividualvariation
Struggle forexistence
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Microbe evolution TODAY
http://www.youtube.com/watch?v=34GeUa7RzvY
http://www.youtube.com/watch?v=W-WumllRPLI&feature=related
Video 1: HIV Evolution on PBS (7:30 min)
Video 2: MDR-TB Evolution on PBS (9 min)