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 (1) Name (2) Year (3) Major  (1) Name (2) Year (3) Major

(1) Name (2) Year (3) Major - PowerPoint Presentation

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(1) Name (2) Year (3) Major - PPT Presentation

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 1 The Unifying Concept in Biology Dr Carol Eunmi Lee ID: 774646

evolution selection hiv evolutionary evolution selection hiv evolutionary genetic host population azt rate natural allele amp reverse change frequencies

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(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 Edition Jon 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 University

Anthropology (Human Evolution)PhD, University of Washington Evolutionary GeneticsPostdoc, University of California, San Diego Evolutionary Physiology and BiochemistryProfessor, University of Wisconsin, Madison Center of Rapid Evolution, Integrative Biology, Genetics

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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

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TA

Background in Geology and Evolutionary BiologyWill lead discussion starting this week (times posted on website)Office Hours: Wed 12:00-2:00 pm, Birge Hall, Room 421

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Juanita Diaz

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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) Overview2) What is Evolution?3) Basic Concepts3) Practical Applications4) 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), 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) Adaptation vs. Plasticity(14) Evolutionary Tradeoffs (Aging)(15, 16) Molecular Evolution(17) Genome Evolution(18, 19) Speciation(20) Earth History, History of Life on Earth(21) Reconstructing the Tree of Life(23) Plant Evolution(24) Animal Evolution(25, 26) Human Evolution

Course Overview

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Introduction What is Evolution? History of Evolutionary Thought No Evolution Hardy Weinberg EquilibriumEvolutionary Genetic DriftMechanisms Genetic Variation (Mutation, Recombination) Epigenetic Variation Natural Selection (including molecular and genome levels)Molecular Evolution Regulatory Evolution Amino Acid Evolution Evolution of Genome ArchitectureMacroevolution Speciation History of Life on Earth Tree of LifeDiversity Plant Evolution Animal Diversity Human Evolution

Structure of Lectures:

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• 3 exams of equal weight, multiple choice: 100 points each = 300 pts total• 3 quizzes: 30 points each = 90 pts total• 3 Homeworks: 210 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)

The increase in fitness over time due to natural selection, or adaptationThe accumulation of mutations, which alter fitness over timeThe change in allele frequencies (or the heritable expression of those alleles) in a population across generationsThe progression into more complex forms of life

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Q: What is Evolution?

Change in proportions of genetically different individuals at each generationLeading 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 offspringBy population, we are referring to a group of interbreeding individuals and their offspring (in the case of sexual species)

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Q1: What is Evolution?(give the most comprehensive answer)

The increase in fitness over time due to natural selection, or adaptationThe accumulation of mutations, which alter fitness over timeThe change in allele frequencies (or the heritable expression of those alleles) in a population across generationsThe progression into more complex forms of life

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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) (Bb) (bb) Blue Purple Red Generation 1: 250 500 250Generation 2: 200 600 200Generation 3: 100 800 100

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

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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) (Bb) (bb) Blue Purple Red Generation 1: 250 500 250Generation 2: 200 600 200Generation 3: 100 800 100

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  genotype frequencies should follow HW expectations, given the allele frequencies

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Q3: How does Evolution Occur?

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Q3: How does Evolution Occur?

***Through 5 Major Mechanisms:Genetic DriftMutationHeritable Epigenetic ModificationMigrationNatural Selection(Think about what forces would change the allele frequencies in a population, or the heritable expression of those alleles)

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

Genetic Drift: totally random changes in allele frequency from generation to generationMutation: 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 anotherNatural 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 variationEpigenetic 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

Biotechnology Agriculture Medicine Conservation

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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 mechanismsI 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 HIV

UNAIDS. 2016 Report on the Global AIDS Epidemic

(http://www.unaids.org/sites/default/files/media_asset/2016-prevention-gap-report_en.pdf)

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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 drugsImplications: AIDS vaccines are unlikely to work on all strains of the virus… …and unlikely to work on a given strain in the long runOur 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

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HIV

Retrovirus with two single strand RNA genomes

Uses the enzyme Reverse Transcriptase to replicate RNA → DNAAttacks 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

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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 Mutations arise, including in the viral reverse transcriptase gene  genetic variationNATURAL 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

Population of HIV individuals with different

reverse transcriptase variants

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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 strain

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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

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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 evolveMust understand evolutionary properties of a disease:Evolutionary historyMutation rateSelective ForcesEvolutionary TradeoffsEvolution in response to drug AZT: slow & accurate vs. fast & sloppy replicationEvolution in response to transmission rate: slow growing & less virulent (keep host alive) vs. fast growing & more virulent

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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 do and 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 arisesNATURAL SELECTION favors reverse transcriptase enzyme that can recognize AZT and not use itThese 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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