Evolution is the unifying concept of biology

Two Central Themes of Biology

Adaptation - How and in what ways doorganisms function and become bettersuited to their environments?

Diversity- What are the evolutionaryrelationships among species andand how do they arise?

Evolution : key points

• 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 areproduced than survive

• Survival and reproduction are not random: individuals that survive and reproduce are ones with the most favorable variations

Evolution is important to many fields of biology

• 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 DataUNAIDS

Change in HIV Prevalence: 1990 vs 2007

Credit: UNAIDS

2007 DataUNAIDS

Prevalence AmongPregnant WomenIn Botswana

HIVHuman

ImmunodeficiencyVirus

Credit: NIAID

Credit: CDC

HIV-I (green)emerging from acultured lymphocyte

Credit: NIAID

Normal T-cells HIV Infected T-cells

AZT blocks reversetranscription

gp120 protein binds to CD4 protein and co-receptor

Kuritzkes D R PNAS 2001;98:13485-13487

©2001 by The National Academy of Sciences

AZT worked initially, but then failed…..Why?

• Mutations of reverse transcriptase occur frequently during viral reproduction

• These mutations yield virions with differenttypes of reverse transcriptase,that differ with respect to AZT inhibition

• Some mutant virions were better able tosurvive and reproduce in an environmentwith AZT than others

• These mutations were passed on to theoffspring of AZT-resistant virions

Why is HIV Fatal?

Evolutionary Biologists Think About Problems From The Perspective of the Organism

Why is it advantageous for me-the-HIV-virus toreplicate so quickly that I kill my host?

So…….

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 towardmore aggressive replication.

3) Eventually, during infection HIV populations evolve the ability to use CXCR4 to gain access to naïve helperT-cells.

4) Virulence may be associated with transmission.

VIRUS DNA VARIATION

Evolution of HIV Within a Single Host

Days Since HIV Infection

0 6 12

X4 virionsOriginate

DuringThe 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.

Natural selection on human populations mayresult in an increase in HIV resistance alleles.

Prediction:

CCR5-delta32

Where did HIV originate?

Phylogeny: a tree that shows the genealogy of a groupof strains, species or populations.

More closely related species should have more similarcharacteristics.

Basic concept underlying a phylogenetic tree:

Phylogeny of SIV and HIVindicates that HIV originatedindependently at least twotimes from non-human primates.

Phylogeny based on reversetranscriptase gene.

Phylogeny based on gp120 gene.

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

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.