Evolution is the unifying concept of biology. Two Central Themes of Biology Adaptation - How and in...
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Evolution is the unifying concept of biology
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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?
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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
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A flowchart of evolutionary reasoning
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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
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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?
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2007 DataUNAIDS
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Change in HIV Prevalence: 1990 vs 2007
Credit: UNAIDS
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2007 DataUNAIDS
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Prevalence AmongPregnant WomenIn Botswana
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HIVHuman
ImmunodeficiencyVirus
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Credit: NIAID
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Credit: CDC
HIV-I (green)emerging from acultured lymphocyte
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Credit: NIAID
Normal T-cells HIV Infected T-cells
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AZT blocks reversetranscription
gp120 protein binds to CD4 protein and co-receptor
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Kuritzkes D R PNAS 2001;98:13485-13487
©2001 by The National Academy of Sciences
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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
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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…….
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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.
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VIRUS DNA VARIATION
Evolution of HIV Within a Single Host
Days Since HIV Infection
0 6 12
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X4 virionsOriginate
DuringThe Infection
Cycle
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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
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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:
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Phylogeny of SIV and HIVindicates that HIV originatedindependently at least twotimes from non-human primates.
Phylogeny based on reversetranscriptase gene.
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Phylogeny based on gp120 gene.
Phylogeny of chimp SIV and HIV indicates that HIV originated independently at least three times from chimp SIV.
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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.