“Nothing in biology

EVOLUTION makes sense except in

the light of evolution”

The Unifying Concept in Biology Theodosius Dobzhansky (1900-1975)

Dr. Carol Eunmi Lee

University of Wisconsin, Madison
Copyright ©2023; do not upload without permission

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Course Website: Introduce Yourself!

Online, in Canvas, 3 pts

http://carollee.labs.wisc.edu/Evolution410.html Year, Major, Course Background, Career Goals, etc.

3 4

Diagnostic Quiz Background needed for this

Online, in Canvas, 3 pts just for taking it course
From Introductory Biology: Some understanding
The score you receive does not count toward your


of basic genetics (Hardy Weinberg Equilibrium,

grade, but this quiz provides an indication of your
DNA, RNA, transcription, translation, allele,
preparation for the course.
genotype)
The quiz covers material you should have learned  Please examine results from the Diagnostic quiz
from Introductory Biology. and assess where your gaps might be

Please study any material that needs reviewing from  You can review your Introductory Biology text on
your Intro Bio textbook. Feel free to reach out to me basic Genetics and Evolution
if you want peer tutoring. 5 6
Reading Who am I?
Carol Lee
(1) Evolutionary Analysis
5th Edition  BA, MA from Stanford University
Jon Herron & Scott Freeman Anthropology (Human Evolution)

 PhD, University of Washington

Evolutionary Genetics
(2) Journal articles posted
Postdoc, University of California, San Diego
on Course Website:


Evolutionary Physiology and Biochemistry

http://carollee.labs.wisc.edu/Evolution
410.html  Professor, University of Wisconsin, Madison
7 Department of Integrative Biology, Genetics 8

Research in TA
my Lab
Patricia
Zito
 Adaptation, Functional Evolutionary
Genomics, Physiological Evolution
 Rapid evolution in response to
BA in Biological Sciences, University of Chicago
climate change, biological invasions, 

and pollution  Research in molecular evolution, speciation, phylogenetics

 Will lead discussion starting next week (times posted on website)
 Arthropod Genome Evolution  Office Hours: Wednesdays 1:00-2:00 pm, or by appointment
9 10

(1) TODAY: What is Evolution? Practical Applications

OUTLINE: (2, 3) History of Evolutionary Thought

(4) Hardy Weinberg Equilibrium (no evolution, null hypothesis)
(5) EVOLUTIONARY MECHANISMS: Genetic Drift
(6, 7, 8) EVOLUTIONARY MECHANISMS: Genetic Variation
1) Overview (9) EVOLUTIONARY MECHANISMS: Epigenetic Inheritance
(10,11,12) EVOLUTIONARY MECHANISMS: Natural Selection
(13, 14) Evolution of Sex, Evolutionary Tradeoffs (Aging)
2) What is Evolution?
(15, 16) Molecular Evolution
(17) Protein Evolution
3) Basic Concepts (18) Genome Evolution
(19, 20) Speciation
3) Practical Applications (21) Earth History, History of Life on Earth
(22) Reconstructing the Tree of Life
4) Example of Evolution in Action: Evolution of HIV (23) Animal Evolution

11
(24, 25) Human Evolution
Course Overview 12
Structure of Lectures:
Assignments & Exams
Introduction What is Evolution?
History of Evolutionary Thought
No Evolution Hardy Weinberg Equilibrium
• 3 exams of equal weight, multiple choice: 100 points
Evolutionary Genetic Drift each = 300 pts total
Mechanisms Genetic Variation (Mutation, Recombination)
Epigenetic Variation
Natural Selection • 3 quizzes: 30 points each = 90 pts total
Molecular Evolution Evolution of New Genes
Protein Evolution Evolution
Evolution of Genome Architecture • 3 homeworks: 70 points each = 210 pts total
Macroevolution Speciation (Link between Micro and Macroevolution)
History of Life on Earth
Tree of Life (Phylogenetics)
**Makeup exams and quizzes are written essay exams
Diversity Animal Diversity
Human Evolution
13 14

Q1: What is Evolution?

Q: What is Evolution?
Q: How does Evolution Occur?

15 16

Q1: What is Evolution? Q: What is Evolution?

(give the most comprehensive answer)
 Change in proportions of genetically different individuals at each
generation
(1) The increase in fitness over time due to natural
selection, or adaptation  Leading to an average change in characteristics of populations
over time à change in allele frequencies (genetic composition)
(2) The accumulation of mutations, which alter fitness or the heritable change in the expression of those alleles
over time (epigenetic inheritance)

(3) The change in allele frequencies (or the heritable  Acts by removing individuals from the population, or by allowing
expression of those alleles) in a population across some to leave more offspring
generations
 By population, we are referring to a group of interbreeding
individuals and their offspring (in the case of sexual species)
(4) The progression into more complex forms of life
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 Q1: What is Evolution? Q1: What is Evolution?
(give the most comprehensive answer) (give the most comprehensive answer)
The change in allele frequencies (or the heritable
expression of those alleles) in a population across
(1) The increase in fitness over time due to natural generations.
selection, or adaptation
(BB) (Bb) (bb)
(2) The accumulation of mutations, which alter fitness Blue Purple Red
over time
Generation 1: 250 500 250
(3) The change in allele frequencies (or the heritable Generation 2: 200 600 200
expression of those alleles) in a population across Generation 3: 100 800 100
generations

(4) The progression into more complex forms of life

19 20

Q1: What is Evolution? Q1: What is Evolution?

(give the most comprehensive answer) (give the most comprehensive answer)
The change in allele frequencies (or the heritable The change in allele frequencies (or the heritable
expression of those alleles) in a population across expression of those alleles) in a population across
generations. generations.

(BB) (Bb) (bb) (BB) (Bb) (bb)

Blue Purple Red Blue Purple Red

Generation 1: 250 500 250 Generation 1: 250 500 250

Generation 2: 200 600 200 Generation 2: 200 600 200
Generation 3: 100 800 100 Generation 3: 100 800 100
Although, even if allele frequencies in a population remain the same
Although, even if allele frequencies in a population remain the across generations, a population is evolving if it goes out of Hardy-
same across generations, a population is evolving if it goes out of Weinberg Equilibrium à genotype frequencies should follow HW
Hardy-Weinberg Equilibrium 21 expectations, given the allele frequencies 22

Q3: How does Evolution Occur?

Q3: How does Evolution Occur?
***Through 5 Major Mechanisms:
 Genetic Drift
 Mutation
 Heritable Epigenetic Modification
 Migration
 Natural Selection

(Think about what forces would change the allele

frequencies in a population, or the heritable
23 expression of those alleles) 24
 i.e. what causes changes in the
allelic composition in a population? Sources of Genetic Variation
 Genetic Drift: totally random changes in allele frequency from
generation to generation Mutation generates
genetic variation
 Mutation: changes in the genetic code, such as errors in DNA
replication, gene deletions or duplications, etc…
Natural Selection Epigenetic Inheritance
changes expression of
 Epigenetic Inheritance: heritable changes that are not due to
changes in DNA sequence itself, but the expression of the DNA, genes
such as changes in DNA methylation and histone modifications, Natural Selection acts on
etc…changes “epi-alleles” not the genetic code (actual alleles) genetic or epigenetic Genetic Drift reduces
variation in a population genetic variation
 Migration: alleles moving from one population to another
 Natural Selection: when some alleles favored over others due to Without genetic or
an increase in fitness (not random); acts on genetic variation in epigenetic variation, Natural
the population 25 Selection cannot occur 26

Evolutionary Concepts
Permeate all Aspects of Agriculture
Biology

Biotechnology
Agriculture  Most of your food is
a product of intense
Medicine artificial selection, or
human induced
Conservation evolution
27 28

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
29 30
 HIV: Fastest HIV Facts
evolving organism
on Earth  AIDS is among the most deadly epidemics in Human History

 As of 2022, 40.4 million have died of AIDS, ~85.6 million have

been infected, and ~39 million people are currently living with
AIDS (WHO 2022 estimate)
HIV infects
macrophages, x10

T-cells UNAIDS, 2020

Report on the
Global AIDS
Epidemic
https://www.unaids.org/en/res
ources/fact-sheet

https://www.unaids.org/sites/d
efault/files/media_asset/2020_
31 aids-data-book_en.pdf 32

Problem :
 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
33 enhanced our understanding of how to combat viruses in general34

HIV How might HIV Evolve?

§ Retrovirus with two single
strand RNA genomes
(1) Drugs impose Selection on HIV:
→ evolution of drug resistance
§ Uses the enzyme Reverse
Transcriptase to replicate
RNA DNA (2) Transmission Rate imposes Selection on HIV:
→ evolution of virulence
§ Attacks host immune
system: infects (3) Host immune system also imposes selection
macrophages and helper on the virus HIV → will not discuss today... Discuss
T cells later
35 36
(1) Natural Selection in Response to Drugs Why does AZT work initially but fail in the long run?
 FAST MUTATION RATE: Lots of Mutations
AZT
Example of an HIV Drug: AZT arise, including in the viral reverse
transcriptase gene à genetic variation
AZT (Azidothymidine) is a thymidine mimic which stops
reverse transcription and impedes viral replication  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)

 The careful reverse transcriptase enzyme is

slow, but the virus is now resistant to AZT
(Tradeoff between fast & sloppy vs. slow & careful
enzyme)
Azido instead of
a hydroxyl group
37 What would happen when AZT therapy stops? 38

Population of HIV individuals with different reverse transcriptase variants

In the presence of AZT, Natural

Selection favors mutants that are
resistant to AZT (blue, have slow &
careful enzyme)

Results in %change in So, what would happen when AZT therapy stops?
the population, toward
higher % of AZT resistant
mutants

Time à
39 40

(2) Selection on Virulence of HIV

Selection on Virulence
 Need to keep host alive long enough to get
passed on to the next host  High Transmission Rate: will select for High Virulence
(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)
41 42
 High Transmission Selection on Virulence
Rate
 Low Transmission Rate: will select for Low Virulence

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”

It’s ok to kill the host, since the chances of jumping to a

new host is high

 Natural selection will favor the MORE virulent strain

43 44

Low Transmission
Rate

 If the virus is not likely to move to a new host the So, how would you select for a
slower growing (and less virulent) strain is likely to
“win”
less harmful strain of HIV?

In this case, It is 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

 Natural selection will favor the LESS virulent strain 45 46

Combating HIV
 Must lower transmission rate of HIV Evolution in Host-Parasite System
so that less fatal strains evolve
SELECTION ON THE HOST (Humans)
 Must understand evolutionary
properties of a disease:
 Some humans have resistance to some HIV
–Evolutionary history
strains. Proportion of people with resistant
–Mutation rate alleles is increasing in some populations.
–Selective Forces
–Evolutionary Tradeoffs
– Evolution in response to drug AZT: slow &  Gene Therapy? Could we win an arms race?
accurate vs. fast & sloppy replication
But HIV evolves faster than we do
– Evolution in response to transmission rate:
slow growing & less virulent (keep host and more quickly than our ability to produce new drugs
alive) vs. fast growing & more virulent 47 48
Why does AZT work initially but fail in the long run?
Questions:
 FAST MUTATION RATE: Mutations in the viral reverse
transcriptase gene of HIV arises
AZT (1) What is Evolution?
 NATURAL SELECTION favors reverse transcriptase
enzyme that can recognize AZT and not use it
(2) How does evolution operate? What are the main
 These mutations slow down the virus (as it becomes Evolutionary Mechanisms?
more careful), but makes the virus resistant to AZT
(Tradeoff between speed vs. accuracy of reverse
transcription) (3) Discuss how an understanding of evolution impacts
practices in Agriculture, Medicine, and Conservation
 What would happen when AZT therapy stops? Back
mutations that restore the Amino Acid sequence to the (4) For example, discuss how different evolutionary
original state are then favored by selection so that mechanisms impact the evolution of HIV, the virus
reverse transcription could speed up again (fast & sloppy that causes AIDS
are favored – because fast replicating mutants would outgrow
the slower) 49 50

Concepts

Evolution
Population
Genetic Drift
Natural
Selection
Mutation
Genetic Variation
Allele, Genotype
HIV, viruses in
general
51