How and in what ways do organisms function and become better suited to their environments?
What are the evolutionary relationships among species and and how do they arise?

• Evolution means change
• Modern organisms are descendants of pre-existing life forms
• The evidence for evolution is overwhelming
• Natural selection is a primary mechanism of evolution

A flowchart of evolutionary reasoning

Evolution via natural selection is a logical outcome given:
• Individuals within species are variable
• Some variations are passed on to offspring
• In every generation, more offspring are produced than survive
• Survival and reproduction are not random: individuals that survive and reproduce are ones with the most favorable variations

• HIV and AIDS research
• AZT worked initially, but then failed….why?
• Why is HIV fatal?
• Why are some people resistant to HIV?
• Where did the HIV virus come from?

2007 Data
UNAIDS

Credit: UNAIDS
Change in HIV Prevalence: 1990 vs 2007

2007 Data
UNAIDS

Prevalence Among
Pregnant Women
In Botswana

Human
Immunodeficiency
Virus

Credit: NIAID

Credit: CDC
HIV-I (green) emerging from a cultured lymphocyte

Normal T-cells HIV Infected T-cells
Credit: NIAID

gp120 protein binds to CD4 protein and co-receptor
AZT blocks reverse transcription

Kuritzkes D R PNAS 2001;98:13485-13487
©2001 by The National Academy of Sciences

• Mutations of reverse transcriptase occur frequently during viral reproduction
• These mutations yield virions with different types of reverse transcriptase, that differ with respect to AZT inhibition
• Some mutant virions were better able to survive and reproduce in an environment with AZT than others
• These mutations were passed on to the offspring of AZT-resistant virions

Why is HIV Fatal?
Evolutionary Biologists Think About Problems From
The Perspective of the Organism
So…….
Why is it advantageous for me-the-HIV-virus to replicate so quickly that I kill my host?

Viruses are Deadly but Short-Sighted
1) They are so good at evolving new epitopes, they rapidly burn through the host’s supply of T-cells.
2) After infection, HIV populations evolve toward more aggressive replication.
3) Eventually, during infection HIV populations evolve the ability to use CXCR4 to gain access to naïve helper
T-cells.
4) Virulence may be associated with transmission.

VIRUS
DNA
VARIATION
Evolution of HIV Within a Single Host
0 6 12
Days Since HIV Infection

X4 virions
Originate
During
The Infection
Cycle

Why are some people resistant to infection by HIV?
Some people have a mutant form of CCR5
(co-receptor) on their CD4 cells.
CCR5-delta32
Prediction:
Natural selection on human populations may result in an increase in HIV resistance alleles.

Where did HIV originate?
Phylogeny: a tree that shows the genealogy of a group of strains, species or populations.
Basic concept underlying a phylogenetic tree:
More closely related species should have more similar characteristics.

Phylogeny of SIV and HIV indicates that HIV originated independently at least two times from non-human primates.
Phylogeny based on reverse transcriptase gene.

Phylogeny of chimp
SIV and HIV indicates that HIV originated independently at least three times from chimp SIV.
Phylogeny based on gp120 gene.

What does Evolutionary Biology have to say about AIDS?
1) Resistance alleles should increase in human and viral populations.
2) The search for a vaccine may be futile.
a) Combinational therapies may slow HIV evolution.
3) The best defense is education.