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Building complexity
Unit 04
Population Dynamics
HIV and humans
From a single cell to a
population…
Single Cells
Population of viruses
Population of humans
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
Genomics and Proteomics
– Genomics is the science of studying whole
genomes.
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 Dynamics
• How do we study populations?
– How do they grow?
– How can we describe them?
• How do populations respond to the
environment?
Population of viruses
in a single person
at the same time
Population of humans
in the same area
at the same time
HIV/AIDS
HIV Disease progression
Animal Viruses
– The reproductive cycle of an enveloped virus
Influenza virus
– Viruses that infect
animals are
common causes
of disease.
– From Medical
Virology 4th Ed.
By White and
Fenner
Simplified Viral Reproductive Cycle
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HIV, the AIDS Virus
– How HIV reproduces inside a CD4 + T lymphocyte
(T cell)
– 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
Integrase
Protease
Glycoproteins
gp120, gp41
– AIDS is
• Acquired immune deficiency syndrome.
• The disease caused by HIV infection.
• Treated with many classes of drugs:
–
–
–
–
HIV drug resistance:
How does this happen?
Reverse transcriptase inhibitors (AZT, ddC,…)
Protease inhibitors
Integrase inhibitors
Fusion inhibitors
http://www.youtube.com
/watch?v=RO8MP3wMv
qg
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.
HIV drug resistance
Initial 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.
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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Natural Selection
– Darwin’s book developed two main points:
• Descent with modification
• Natural selection
EVOLUTION
The Mechanism of
EVOLUTION
– 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.
Darwin’s Inescapable
Conclusion
– Fact 1: Potential for overproduction and
competition for existence
– Fact 2: Individual variation
– The inescapable conclusion:
Unequal reproductive success
–Fourteen species of Galápagos finches have beak
shapes adapted to suit their environments.
• Darwin called this process natural selection.
• The result of natural selection is adaptation.
Observing Artificial Selection
Artificial 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
How do we study
overproduction and struggle
for existence?
Look to Ecology
Darwin’s Inescapable
Conclusion
– Fact 1: Potential for overproduction
and competition for existence
Evidence
for HIV?
– Fact 2: Individual variation
– The inescapable conclusion:
Unequal reproductive success
• Darwin called this process natural selection.
• The result of natural selection is evolution when a population
has adapted to its environment.
A Hierarchy of Interactions
– Ecology
• Is the scientific study of the interactions
between organisms and their environments.
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
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
5
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.
Figure 18.17
– A comparison of the logistic growth model
and the exponential growth model
Copyright © 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings
HIV Disease progression:
Modified Logistic Growth Model
–Carrying capacity
•Is the number of individuals in a population that the
environment can just maintain with no net increase
or decrease.
Darwin’s Inescapable
Conclusion
Random Mutations in the
genome are the basis of
individual variation
• Base substitution
– Fact 1: Potential for overproduction and
competition for existence
– Fact 2: Individual variation
HIV can reproduce over a billion times a day.
It is in a constant struggle for existence
with the immune system
Evidence
for HIV?
– The inescapable conclusion:
Unequal reproductive success
• Darwin called this process natural selection.
• The result of natural selection is evolution when a
population has adapted to its environment.
– 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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An Example of
Mutations that have an
effect on drug response
in humans.
– In 2003, the Food and Drug
Administration
– 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.
• 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
How do mutations cause drug
resistance?
How does the
anti-HIV drug
AZT work?
• http://www.cabm.rutgers.edu/~kalyan/RT_imgs/index.html
– Dr. Kalyan Das at Rutgers University
Figure 10.1
How do mutations in the
genome cause resistance?
How do mutations in the
genome cause resistance?
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Natural Selection at work
Time 0:
Overproduction and
pre-existing individual variation
caused by random mutations
Time 1:
Struggle for existence:
Environmental
Selection
HIV drug resistance! How??
1.
Overproduction
Heritable
Individual
variation
2.
3.
Struggle for 4.
existence
HIV replicates over a billion times a day
Reverse transcriptase (RT) is error-prone!
•
5.
Time 2:
Population
has evolved
Large amount of offspring
•
About 50% of HIV DNA transcripts made by RT
contain at least one mistake (mutation) at random.
Random mutation is heritable
Mutants are better able to reproduce in
selective environment
Population adapts to change in environment,
resulting in a different population = evolution
Microbe evolution TODAY
Video 1: HIV Evolution on PBS (7:30 min)
Video 2: MDR-TB Evolution on PBS (9 min)
http://www.youtube.com/watch?v=
34GeUa7RzvY
http://www.youtube.com/watch?v=
W-WumllRPLI&feature=related
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