on your notecards please write the following: evolution · evolution 410 9/9/19 professor carol lee...

Evolution 410 9/9/19

Professor Carol Lee 1

(1) Name(2) Year(3) Major(4) Courses taken in Biology(4) Career goals(5) Email address(6) Why am I taking this class?

On your Notecards please write the following:

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The Unifying Concept in Biology

Dr. Carol Eunmi LeeUniversity of Wisconsin, Madison

EVOLUTION

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Theodosius Dobzhansky (1900-1975)

“Nothing in biology makes sense except in the light of evolution”

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Reading(1) Evolutionary Analysis

5th EditionJon Herron & Scott Freeman

(2) Journal articles posted on Course Website:

http://carollee.labs.wisc.edu/Evolution410.html

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Who am I?

■ BA, MA from Stanford UniversityAnthropology (Human Evolution)

■ PhD, University of WashingtonEvolutionary Genetics

■ Postdoc, University of California, San DiegoEvolutionary Physiology and Biochemistry

■ Professor, University of Wisconsin, MadisonCenter of Rapid Evolution, Integrative Biology, Genetics 5

Research in my Lab

■ 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)

■ Arthropod Genome Evolution 6



TA

■ Master’s Degrees in Marine Biology and Ecology■ Will lead discussion starting this week (times posted on

website)

■ Office Hours: Wed 12:00-2:00 pm, Birge Hall, Room 4217

Teresa Popp(Juanita Diaz, last year’s TA, might also help)

Juanita Diaz

Teresa Popp

Course Website:

http://carollee.labs.wisc.edu/Evolution410.html

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Background needed for this course

■ Some understanding of basic genetics (Hardy Weinberg Equilibrium, DNA, RNA, transcription, translation, allele, genotype)

■ Please review your Introductory Biology text on basic Genetics

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1) Overview

2) What is Evolution?

3) Basic Concepts

3) Practical Applications

4) Example of Evolution in Action: Evolution of HIV

OUTLINE:

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(1) TODAY: What is Evolution? Practical Applications(2, 3) History of Evolutionary Thought(4) Hardy Weinberg Equilibrium (no evolution)(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 (Aging)(14) Molecular Evolution(15) Protein Evolution(16) Genome Evolution(17, 18) Speciation(19.20) Earth History, History of Life on Earth(22) Reconstructing the Tree of Life(21) Plant Evolution(23) Animal Evolution(24, 25) Human Evolution

Course Overview11

Introduction What is Evolution? History of Evolutionary Thought

No Evolution Hardy Weinberg Equilibrium

Evolutionary Genetic DriftMechanisms Genetic Variation (Mutation, Recombination)

Epigenetic VariationNatural Selection

Molecular Evolution Evolution of New GenesProtein Evolution EvolutionEvolution of Genome Architecture

Macroevolution Speciation (Link between Micro and Macroevolution)History of Life on EarthTree of Life

Diversity Plant EvolutionAnimal DiversityHuman Evolution

Structure of Lectures:

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• 3 exams of equal weight, multiple choice: 100 points each = 300 pts total

• 4 quizzes: 30 points each = 120 pts total

• 3 homeworks: 60 points each = 180 pts total

Assignments & Exams

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Q: What is Evolution?

Q: How does Evolution Occur?

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Q1: What is Evolution?

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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 life16

Q: What is Evolution?■ Change in proportions of genetically different individuals at

each generation

■ Leading to an average change in characteristics of populations over time à 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)

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(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 life18




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

(BB) (Bb) (bb)Blue Purple Red

Generation 1: 250 500 250Generation 2: 200 600 200Generation 3: 100 800 100

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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 20





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 à genotype frequencies should follow HW expectations, given the allele frequencies 21

Q3: How does Evolution Occur?

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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 expression of those alleles) 23

i.e. what causes changes in the allelic composition in a population?

■ Genetic Drift: totally random changes in allele frequency from generation to generation

■ Mutation: changes in the genetic code, such as errors in DNA replication, gene deletions or duplications, etc…

■ 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…changes “epi-alleles” not the genetic code (actual alleles)

■ 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

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Natural Selection

Without genetic or epigenetic variation, Natural Selection cannot occur

Mutation generates genetic variation

Epigenetic Inheritance changes expression of genes

Genetic Drift reduces genetic variation

Sources of Genetic Variation

Natural Selection acts on genetic or epigenetic variation in a population

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Evolutionary Concepts Permeate all Aspects of Biology

BiotechnologyAgriculture

Medicine

Conservation26

Agriculture

■ Most of your food is a product of intense artificial selection, or human induced evolution

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Human-induced Evolution

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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

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HIV infects macrophages, T-cells

HIV: Fastest evolving organism on Earth

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HIV Facts■ AIDS is among the most deadly epidemics in Human

History (1981-2012: ~36 million deaths)

■ ~78 million have been infected, ~36.7 million people currently living with AIDS (estimated 2015)

■ 90 million deaths predicted by 2020

#people living with HIVUNAIDS. 2016 Report on the Global AIDS Epidemic

(http://www.unaids.org/sites/default/files/media_asset/2016-prevention-gap-report_en.pdf) 31 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 enhanced our understanding of how to combat viruses in general33

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

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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 today... Discuss later

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(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

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Why does AZT work initially but fail in the long run?

■ FAST MUTATION RATE: Lots of Mutationsarise, including in the viral reverse transcriptase gene à 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)

■ The careful reverse transcriptase enzyme is slow, but the virus is now resistant to AZT (Tradeoff between fast & sloppy vs. slow & careful enzyme)

■ What would happen when AZT therapy stops?

AZT

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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

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Time à

Population of HIV individuals with different reverse transcriptase variants

So, what would happen when AZT therapy stops?

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(2) Selection on Virulence of HIV

■ 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)

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Selection on Virulence■ High Transmission Rate: will select for High Virulence

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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”

■ 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 strain42



Selection on Virulence■ Low Transmission Rate: will select for Low Virulence

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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”

■ 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

■ Natural selection will favor the LESS virulent strain 44

So, how would you select for a less harmful strain of HIV?

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Combating HIV■ 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 46

Evolution in Host-Parasite System

SELECTION ON THE HOST (Humans)

■ 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 doand more quickly than our ability to produce new drugs

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Why does AZT work initially but fail in the long run?

■ 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

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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

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EvolutionPopulationGenetic DriftNatural SelectionMutationGenetic VariationAllele, GenotypeHIV

Concepts

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on your notecards please write the following: evolution · evolution 410 9/9/19 professor carol lee...

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