Evolution is the unifying concept of biology

Two Central Themes of Biology Adaptation - How and in what ways do organisms function and become better suited to their environments? Diversity- What are the evolutionary relationships among species and and 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 are produced 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 Data UNAIDS

Change in HIV Prevalence: 1990 vs 2007 Credit: UNAIDS

2007 Data UNAIDS

Prevalence Among Pregnant Women In Botswana

HIV Human Immunodeficiency Virus

Credit: NIAID

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

Credit: NIAID Normal T-cellsHIV Infected T-cells

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

Kuritzkes D R PNAS 2001;98: ©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 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 Why is it advantageous for me-the-HIV-virus to replicate 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 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 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. Natural selection on human populations may result in an increase in HIV resistance alleles. Prediction: CCR5-delta32

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

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 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.