Unit 04Population Dynamics

HIV and humans

Building complexityFrom 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.

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

Population Dynamics

• How do we study populations? – How do they grow?– How can we describe them?

• How do populations respond to the environment?

HIV/AIDS

HIV Disease progression

Animal Viruses

– Viruses that infect animals are common causes of disease.

– From Medical Virology 4th Ed. By White and Fenner

– The reproductive cycle of an enveloped virus

Simplified Viral Reproductive Cycle

Influenza virus

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

– How HIV reproduces inside a CD4 + T lymphocyte (T cell)

Integrase

Protease

Glycoproteins gp120, gp41

– 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

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.

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.

The Darwinian View of Life

The evolutionary view of life came into focus in 1859 when Charles Darwin published The Origin of Species.

– Darwin’s book developed two main points:

• Descent with modification

• Natural selection

EVOLUTION

The Mechanism of EVOLUTION

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.

–Fourteen species of Galápagos finches have beak

shapes adapted to suit their environments.

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.

Observing Artificial SelectionArtificial selection is the selective breeding of domesticated plants and animals by humans.

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

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?

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.

A Hierarchy of Interactions

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

Figure 18.17

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

– 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.

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

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.

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?

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

– 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.

– 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.

Figure 10.1

How does the anti-HIV drug AZT work?

How do mutations cause drug resistance?

• http://www.cabm.rutgers.edu/~kalyan/RT_imgs/index.html

– Dr. Kalyan Das at Rutgers University

How do mutations in the genome cause resistance?

How do mutations in the genome cause resistance?

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

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

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)