Transcript Lecture PPT - Carol Lee Lab - University of Wisconsin

On your Notecards please write the following:
(1) Name
(2) Year
(3) Major
(4) Courses taken in Biology
(4) Career goals
(5) Email address
(6) Why am I taking this class?
EVOLUTION
The Unifying Concept in Biology
Dr. Carol Eunmi Lee
University of Wisconsin, Madison
“Nothing in biology
makes sense except in
the light of evolution”
Theodosius Dobzhansky (1900-1975)
Reading
(1) Evolutionary Analysis
5th Edition, 2013
Jon Herron & Scott Freeman
(2) Journal articles posted
on Course Website
Who am I?
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BA, MA from Stanford University
Anthropology (Human Evolution)
PhD, University of Washington
Evolutionary Genetics
Postdoc, University of California, San Diego
Evolutionary Physiology and Biochemistry
Professor, University of Wisconsin, Madison
Center of Rapid Evolution, Zoology, Genetics
Research in
my Lab
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Adaptation, Functional Evolutionary
Genomics, Physiological Evolution
Rapid evolution of invasive species
entering the Great Lakes (zebra
mussels, quagga mussels, copepods)
Evolution of waterborne infectious
diseases carried by these invaders
(cholera)
TA
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Tiago Ribeiro, Master’s degree in Genetics and
Evolutionary Biology
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Will lead discussion on Fridays, starting next week (times
posted on website)
Office Hours: Mondays Noon-2 pm, Birge Hall, Room 422
Course Website
http://carollee.labs.wisc.edu/Evolution410.html
Background needed for this
course
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Some understanding of basic genetics
(Hardy Weinberg Equilibrium, DNA,
RNA, transcription, translation, allele,
genotype)
OUTLINE:
1) Overview
2) What is Evolution?
3) Basic Concepts
3) Practical Applications
4) Example of Evolution in Action: Evolution of HIV
(1) TODAY: What is Evolution? Practical Applications
(2, 3) History of Evolutionary Thought
(4) Hardy Weinberg Equilibrium (no evolution), Genetic Drift
(5) EVOLUTIONARY MECHANISMS: Genetic Drift
(6, 7, 8) EVOLUTIONARY MECHANISMS: Genetic Variation
(9) EVOLUTIONARY MECHANISMS: Epigenetic Inheritance
(10,11,12) EVOLUTIONARY MECHANISMS: Natural Selection
(13) Evolutionary Tradeoffs
(14) Adaptation vs. Plasticity
(15, 16) Molecular Evolution
(17) Genome Evolution
(18, 19) Speciation
(20, 21) Earth History, History of Life on Earth
(22) Reconstructing the Tree of Life
(23) Microbial Evolution
(24) Plant Evolution
(25) Animal Diversity
(26, 27) Human Evolution
Course Overview
Structure of Lectures:
Introduction
&Background
What is Evolution? Practical Applications
History of Evolutionary Thought
No Evolution
Hardy Weinberg Equilibrium
Evolutionary
Mechanisms
Genetic Drift
Genetic Variation (Mutation, Recombination)
Epigenetic Variation
Natural Selection
(including molecular and genome levels)
Macroevolution
Speciation
History of Life on Earth
Tree of Life
Diversity
Microbial Evolution
Plant Evolution
Animal Diversity
Human Evolution
Grading & Exams
• 3 exams of equal weight, multiple choice:
100 points each = 300 pts total
• 3 quizzes: 20 points each = 60 pts total
• 3 homeworks: 30 points each = 90 pts total
300 (exams) + 60 (quizzes) + 90 pts (homework)
= 450 points total
Q: What is Evolution?
Q: How does Evolution Occur?
Q1: What is Evolution?
Q1: What is Evolution?
(give the most comprehensive answer)
(1) The increase in fitness over time due to natural
selection, or adaptation.
(2) The accumulation of mutations, which alter fitness
over time.
(3) The change in allele frequencies (or the heritable
expression of those alleles) in a population across
generations.
(4) The progression into more complex forms of life
Q1: What is Evolution?
(give the most comprehensive answer)
The change in allele frequencies (or the heritable
expression of those alleles) in a population across
generations.
(BB)
Blue
Generation 1:
Generation 2:
Generation 3:
(Bb)
Purple
250
200
100
500
600
800
(bb)
Red
250
200
100
Although, even if allele frequencies in a population remain the
same across generations, a population is evolving if it goes
out of Hardy-Weinberg Equilibrium (more on this later)
Q: What is Evolution?
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Change in proportions of genetically different individuals at
each generation
Leading to an average change in characteristics of
populations over time  change in allele frequencies
(genetic composition) or the heritable change in the
expression of those alleles (epigenetic inheritance)
Acts by removing individuals from the population, or by
allowing some to leave more offspring
By population, we are referring to a group of interbreeding
individuals and their offspring (in the case of sexual species)
Q3: How does Evolution Occur?
Q3: How does Evolution Occur?
***Through
5 Major Mechanisms:
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Genetic Drift
Mutation
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Heritable Epigenetic Modification
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Migration
Natural Selection
(Think about what forces would change the allele
frequencies in a population, or the heritable
expression of those alleles)
i.e. what causes changes in the
allelic composition in a population?
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Genetic Drift: totally random changes in allele frequency
from generation to generation
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Mutation: changes in the genetic code, such as errors in
DNA replication, gene deletions or duplications, etc…
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Epigenetic Inheritance: heritable changes that are not
due to changes in DNA sequence itself, but the expression
of the DNA, such as changes in DNA methylation and
histone modifications, etc…
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Migration: alleles moving from one population to another
Natural Selection: when some alleles favored over others
due to an increase in fitness (not random); acts on genetic
variation in the population
Sources of Genetic Variation
Mutation generates
genetic variation
Natural Selection
Natural Selection acts on
genetic or epigenetic
variation in a population
Epigenetic modification
changes expression of
genes
Genetic Drift reduces
genetic variation
Without genetic or
epigenetic variation,
Natural Selection cannot
Evolutionary Concepts
Permeate all Aspects of
Biology
Biotechnology
Agriculture
Medicine
Conservation
Agriculture
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Most of your food is
a product of intense
artificial selection, or
human induced
evolution
Evolution of a
Pathogen as an
Example:
I will now use an infectious disease to illustrate
basic evolutionary concepts.
The following example illustrates several
evolutionary mechanisms
I will explain these concepts in more detail over
the next few lectures
HIV: Fastest
evolving organism
on Earth
HIV infects
macrophages,
T-cells
HIV Facts
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AIDS is among the most deadly epidemics in Human
History (1981-2012: ~36 million deaths)
~75 million have been infected, ~35.3 million people
currently living with AIDS (estimated 2012)
90 million deaths predicted by 2020
#people living with HIV
UNAIDS. 2012
Report on the Global
AIDS Epidemic
(http://www.avert.org/w
orldwide-hiv-aidsstatistics.htm)
A global view of HIV infection
33 million people [30–36 million] living with HIV, 2007
Problem :
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HIV has the fastest mutation rate of any virus or
organism observed to date
HIV evolves more rapidly than humans, and more
quickly than the ability of humans to produce new
drugs
Implications: AIDS vaccines are unlikely to work on all
strains of the virus… …and unlikely to work on a given
strain in the long run
Our understanding of how to combat viruses had in general been
poor, and the recent intensive research on HIV has greatly
enhanced our understanding of how to combat viruses in general
HIV
 Retrovirus with two single
strand RNA genomes
 Uses the enzyme Reverse
Transcriptase to replicate
RNA
DNA
 Attacks host immune
system: infects
macrophages and helper T
cells
How might HIV Evolve?
(1) Drugs impose Selection on HIV:
→ evolution of drug resistance
(2) Transmission Rate imposes Selection on HIV:
→ evolution of virulence
(3) Host immune system also imposes selection on the
virus HIV → will not discuss
(1) Natural Selection in Response to Drugs
Example of an HIV Drug: AZT
AZT (Azidothymidine) is a thymidine mimic which stops
reverse transcription and impedes viral replication
Why does AZT work initially but fail in the long run?
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FAST MUTATION RATE: Lots of Mutations
arise, including in the viral reverse
transcriptase gene  genetic variation
NATURAL SELECTION favors reverse
transcriptase enzyme mutant that can
recognize AZT and not use it (meaning the
ones with the mutant now live, the others die)
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The careful reverse transcriptase enzyme
is slow, but the virus is now resistant to
AZT (Tradeoff between fast & sloppy vs.
slow & careful enzyme)
AZT
• In the presence of AZT, Natural
Selection favors mutants that
are resistant to AZT (blue, have
slow & careful enzyme)
Results in %change in
the population, toward
higher % of AZT
resistant mutants
So, what would happen when AZT therapy stops?
(2) Selection on Virulence of HIV
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Need to keep host alive long enough to get
passed on to the next host
(Evolutionary Tradeoff between fast viral population
growth versus keeping the host alive)
 High
Transmission rate : High Virulence
(Can grow fast and jump to the next host; ok if host dies;
the genetic strain that grows faster will win)
 Low
Transmission Rate : Low Virulence
(More virulent strains would die with the host and get
selected out; less virulent strain that does not kill the
host will win)
Selection on Virulence
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High Transmission Rate: will select for High Virulence
High Transmission Rate
If the virus is likely to move to a new host, the faster
growing (and more virulent) strain is likely to overtake
the slower strains and “win”
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It’s ok to kill the host, since the chances of jumping to
a new host is high
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Natural selection will favor the MORE virulent strain
Selection on Virulence
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Low Transmission Rate: will select for Low Virulence
Low Transmission Rate
If the virus is not likely to move to a new host the
slower growing (and less virulent) strain is likely to
“win”
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It’s not ok to kill the host, since the chances of jumping
to a new host is low. If the virus kills the host, it will kill
itself
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Natural selection will favor the LESS virulent strain
So, how would you select for a less harmful
strain of HIV?
Combating HIV
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Must lower transmission rate of HIV
so that less fatal strains evolve
Must understand evolutionary
properties of a disease:
–Evolutionary history
–Mutation rate
–Selective Forces
–Evolutionary Tradeoffs
– Evolution in response to drug AZT: slow &
accurate vs. fast & sloppy replication
– Evolution in response to transmission rate:
slow growing & less virulent (keep host
alive) vs. fast growing & more virulent
Evolution in Host-Parasite System
SELECTION ON THE HOST (Humans)
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Some humans have resistance to some HIV
strains. Proportion of people with resistant
alleles is increasing in some populations.
Gene Therapy? Could we win an arms race?
But HIV evolves faster than we do
and more quickly than our ability to produce new drugs
Questions:
(1) What is Evolution?
(2) How does evolution operate? What are the main
Evolutionary Mechanisms?
(3) Discuss how an understanding of evolution impacts
practices in Agriculture, Medicine, and Conservation
(4) For example, discuss how different evolutionary
mechanisms impact the evolution of HIV, the virus
that causes AIDS
Why does AZT work initially but fail in the long run?
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FAST MUTATION RATE: Mutations in the viral reverse
transcriptase gene of HIV arises
NATURAL SELECTION favors reverse transcriptase
enzyme that can recognize AZT and not use it
These mutations slow down the virus (as it becomes
more careful), but makes the virus resistant to AZT
(Tradeoff between speed vs. accuracy of reverse
transcription)
What would happen when AZT therapy stops? Back
mutations that restore the Amino Acid sequence to the
original state are then favored by selection so that
reverse transcription could speed up again (fast & sloppy
are favored – because fast replicating mutants would outgrow
the slower)
AZT
Concepts
Evolution
Population
Genetic Drift
Natural Selection
Mutation
Genetic Variation
Allele, Genotype
HIV