Download Lecture 2 : Evolution is the unifying concept of biology

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
HIV-I (green)
emerging from a
cultured lymphocyte
Credit: CDC
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
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
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.
Evolution of HIV Within a Single Host
VIRUS
DNA
VARIATION
0
6
Days Since HIV Infection
12
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.