1. Why study Evolutionary Biology PDF

Preview

Summary

1. Why study Evolutionary Biology. Lecture Notes. Summer 2021...

Description

5/4/2021

WHY STUDY EVOLUTIONARY BIOLOGY? Introduction to EEB214 Evolution and Adaptation Summer 2021 Lecture Week 1, Day 1, lecture 1

1

We could study evolution …. • Outline: • To address a current problem • Zika virus • Is HIV an evolutionary

problem?

• To prepare for studying

biology • Outline of the course

objectives

https://flic.kr/p/R5KdaM

• To make sense of the

world we inhabit • Topics to be covered

2

1

5/4/2021

To address a problem: Zika virus • Zika virus in the Polynesia

disease outbreak is similar to the virus in the more recent South American outbreak

Lazear & Diamond 2016 J. Virol. 90, 4864-75

3

*Lecture Schedule (but always check the current one on quercus!) Lect Day

Lecture topic

Chap ter in text

Lecture Tutorial Quiz (LTQ)

Assignment

1

Methods in Evolution

1 &4

office hours

2

Natural selection and trees

1&2

LTQ1 (Sticklebacks)

3

Patterns & Variation

3&4

LTQ2 (Lizards)

4

Variation among individuals

5

Mendel, and populations

6

Population, selection & Migration

7

Evolutionary genetics and species

5&6

LTQ5 (Hbs)

8

Adaptation

2&5

(office hours)

9

Life history and behaviour

7

LTQ6 (Lactose)

10

Behaviour and adaptations

6&7

3rd June 2021

TEST 2

11

Evolution, developmentand genes

LTQ7 (limbs)

Poster assignment

12

Review

LTQ3 (Birds) 3&5

18th May 2021

TEST 1

LTQ4 (Mice)

8

LTQ8 (virus)

4

2

5/4/2021

*Lecture Schedule (but always check the current one on quercus!)

Grade outline Assignment description

Due date

Weight % of assignment

Term Test 1

18 May 2021

18

Term Test 2

3 June 2021

18

Online Assessments (OA)

Ongoing “pop” quizzes (best 3 )

6

Poster Assignment

8 June 2021

8

Lecture Tutorial Quizzes (LTQ)

Ongoing (best 6)

18

Discussion blogs (Packback)*

Ongoing (best 5*)

5

Final exam

TBA

27

5

Required Materials • Lectures:___________ • Text: Charlesworth, B. & Charlesworth, D. 2017 Evolution:

a very short introduction. Oxford University Press. ISBN 978-0-19-880436-9 available from Redshelf: • (for eText see link to Redshelf), see U of T bookstore

• Other readings (see Quercus Course Reserves) • Packback (Packback.ca) • Assignments: _____________ • Poster assignment: • For example…….

1-6

6

3

5/4/2021

To address a current problem • Scientist use the scientific method • The scientific method is: • Make observations • Propose ideas • Test ideas • Discard or modify ideas based on results • (Belk & Maier 2018 Biology science for life, Pearson)

• Comte de Buffon’s method circa 1774: (see text ch 4) • __________________________ • __________________________ • __________________________

7

Observations and hypotheses • Observation: • Hypothesis: • A hypothesis is an explanation for an observation that requires testing for validation (Belk & Maier 2018 Biology science for life, Pearson); • A testable hypothesis leads to predictions • Scientific hypotheses are: • Testable • Falsifiable • Prediction: E.g. If __________ then _____

8

4

5/4/2021

Observations and hypotheses • Observation: • Human immunodeficiency virus (HIV) becomes resistant to

antiviral drugs • Hypothesis: • A hypothesis is an explanation for an observation that requires testing for validation (Belk & Maier 2018 Biology science for life, Pearson); • A testable hypothesis leads to predictions • Scientific hypotheses are: • Testable • Falsifiable • Prediction: • E.g. If HIV is caused by a virus then treatment with antiviral drugs will __________

9

To address a current problem • Observation: • Human immunodeficiency virus (HIV) becomes resistant

to antiviral drugs • Question: • Is HIV an evolutionary problem?

• Q: How could analyses used in evolutionary biology

provide an answer to __________ • E.g. HIV …,

10

5

5/4/2021

Time course of HIV infection Virus titre 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0

Virus titre Modified from Belk & Maier 2013 Biology Science for life 4th Ed. Pearson

11

Antiretroviral drug therapy

Goldberg et al 2012 Cell 148 p.1271

12

6

5/4/2021

Bergstrom & Dugatkin 2016 Evolution 2nd Edition. WW Norton

13

Q: How could analyses used in evolutionary biology provide an answer to _antiretroviral drug resistance in HIV ?__ • “ The idea behind multidrug therapy for HIV is to increase

the number of mutations required for resistance and thus reduce genetic variation in the viral population for survival in the presence of drugs. Could we achieve the same effect by using antiretroviral drugs in sequence instead of simultaneously? See article by Gulick et al. 1998 JAMA 280:35” • Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson.

14

7

5/4/2021

HIV an evolutionary problem • The question asks • “Why do therapies using just one drug, and sometimes therapies using multiple drugs, work well at first but ultimately fail?” • Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

• What is HIV? What is AIDS? ___________ • How can we find out information for the question which

refers to multidrug resistance? • Some drugs target an enzyme the virus uses to copy itself

15

Reverse Transcriptase: E.g. HIV

© 2012 by K.D.Williams -UTSC

Biology. Russell et al. 2012 Nelson Education Ltd.

16

8

5/4/2021

HIV an evolutionary problem

1

17

What does the media say about AIDS in Canada? • Human Immunodeficiency Virus (HIV) is also a problem in

Canada and, in some communities, it is spreading! • Youtube video link of HIV rates in Saskatchewan • https://youtu.be/5tydyioJJw8

There is drug resistance. “Funding cuts spark fears about the rise of drug-resistant strains of HIV in Africa” Glauser & Simon 2010 CMAJ 182:3 p.E165 DOI: 10.1503/cmaj.109-3149 http://dx.doi.org.myaccess.library.utoronto.ca/10.1503/cmaj.1093149

In the nineties there was hope drugs would cure AIDS. In 1996 Buffalo news reported that a cocktail of 3 drugs “wiped out the HIV virus” Osterman C. Buffalo News 12 July 1996

https://flic.kr/p/8nzDGb pills 2

18

9

5/4/2021

What does the media say about AIDS in Canada? • Human Immunodeficiency Virus (HIV) is also a problem in

Canada and, in some communities, it is spreading! • Youtube video link of HIV rates in Saskatchewan • https://youtu.be/5tydyioJJw8

There is drug resistance. “Funding cuts spark fears about the rise of drug-resistant strains of HIV in Africa” Glauser & Simon 2010 CMAJ 182:3 p.E165 DOI: 10.1503/cmaj.1093149 http://dx.doi.org.myaccess.library.utoronto.ca/10.1503/cmaj.109-3149

https://flic.kr/p/KDPuS Pills. E.g. Azidothymidine (AZT)

In the nineties there was hope drugs would cure AIDS. In 1996 Buffalo news reported that a cocktail of 3 drugs “wiped out the HIV virus” Osterman C. Buffalo News 12 July 1996

2

19

How does drug resistance arise? • Drugs like AZT are used to treat HIV infections because the

inhibit the ability of the virus to copy itself many times: AZT is a reverse transcriptase inhibitor. • Reverse transcriptase is an enzyme that catalyzes the copying of the RNA into DNA (opposite to the direction for making proteins: DNA to RNA to Protein) • Gulick & Mellors et al. [1] describe the effects of many studies that either gave the drugs simultaneously or sequential and the outcomes of each type of treatment • Goldberg et al [2] reviews how multidrug resistance happens: when patients do not take their pills and the virus replicates accumulating mutations that suppress the effectiveness of the drug. Resistant viral strains can then continue to survive even if some of the drugs are in the patient’s system. 3

20

10

5/4/2021

Multidrug treatments cannot reduce the variation in resistance if given sequentially

4

21

Multidrug treatments cannot reduce the variation in resistance if given sequentially Sequential treatment

• Treatment with drugs

each of which with a different type of action. Consequently different genetic variants for resistance to the drug within the virus population evolve

https://flic.kr/p/ay7LqQ

Simultaneous treatment

• Treating with more than

one drug at a time reduces resistance because fewer virions will have both (or multiple) types of resistance mutations

https://flic.kr/p/8nzDGb pills

4

22

11

5/4/2021

Conclusions • Understanding the ability of HIV to change really is

important: • because of evolution the increased survivorship of viruses with

genetic resistance to the drugs is a challenge, • Because it improves our ability to treat HIV because it contributes

to a greater compliance among HIV-infected people receiving drug treatments.

5

23

References and further reading on HIV • References cited 1. Glauser, W. & Simon, B. (2010) Funding cuts spark fears about the rise of drug-resistant strains of HIV in Africa. CMAJ 182:3 p.E165 DOI: 10.1503/cmaj.109-3149 2. Gulick, R. M. & Mellor, J.W. et al. (1998) Simultaneous vs sequential initiation of therapy with Indinavir, Zidovudine, and Lamivudine for HIV-1 infection: 100-week follow-up. JAMA 280:35 3. Goldberg et al. 2012 Outwitting Evolution: fighting drug resistant TB, malaria and HIV. Cell 148:1271-1283 4. Osterman C. Buffalo News 12 July 1996

• Further reading: • Hogg, R. S. et al. (2012) Disparities in the burden of HIV/AIDS in Canada. PLoS One 349260 • Yang Q. et al 2010 Estimates of the number of prevalent and incident Human Immunodeficiency Virus (HIV) infections in Canada, 2008. Can J Public Health 101: 486

6

24

12

5/4/2021

To prepare for studying biology • To prepare for research in evolutionary biology

25

To prepare for research in evolutionary biology

Daniel E. Goldberg, Robert F. Siliciano, William R. Jacobs Jr. null, Volume 148, Issue 6, 2012, 1271–1283 http://dx.doi.org/10.1016/j.cell.2012.02.021

26

13

5/4/2021

To prepare for research in evolutionary biology • Research into drugs that stop viruses reproducing

RT inhibitors

Protease inhibitors

Chemokine Receptors

Fusion inhibitors

Integrase inhibitors

27

FIGURE 1-3B

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

28

14

5/4/2021

Using the scientific process to study HIV • Question: • How does AZT treatment change the genetic variation for resistance to the drug within the virus population? • Hypothesis: • AZT treatment may change the number of genetic variants for resistance to the drug within the virus population • Prediction: • Larder et al (1989) predicted that the samples of virus that could be cultured on plates treated with AZT would increase over the 2 to 20 months of treatment as the population of resistant virions grew • Methods: • Results: • Discussion: • Conclusions

29

AZT is a drug that makes reverse transcriptase ineffective

RT inhibitors

30

15

5/4/2021

FIGURE 1-10

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

31

How does AZT treatment change the resistance to the drug within the virus population? Scientific Process

• Question:

Question

• How does AZT treatment

change the genetic variation for resistance to the drug within the virus population?

• Hypothesis: • Prediction: • Methods: • Results:

•

• Discussion: • Conclusions:

32

16

5/4/2021

AZT treatment changes incidence of the genetic variants for resistance to the drug within the virus population Hypothesis

Scientific Process

• Question:

• AZT treatment may

change number of genetic variants for resistance to the drug within the virus population

• Hypothesis: • Prediction: • Methods: • Results:

•

• Discussion: • Conclusions:

33

The samples of virus that could be cultured on plates treated with AZT would increase over the many months of the treatment Scientific Process

• Question:

Hypothesis

• Larder et al (1989)

predicted that the samples of virus that could be cultured on plates treated with AZT would increase over the 2 to 20 months of treatment as the population of resistant virions grew.

• Hypothesis: • Prediction: • Methods: • Results: • Discussion: • Conclusions: • 34

17

5/4/2021

Using the scientific process to study HIV • Methods: • Larder et al (1989) measured the percentage of resistant virions present in samples from patients. These samples were taken at regular intervals over the AZT treatment. The percent resistance was then plotted against the concentration of AZT typically used to reduce HIV replication. • Results: • AZT treatment was associated with an increase in the incidence resistance to the drug within the virus population • AZT resistance arises quickly in about 6 months • Discussion: • Conclusions: • Over time the AZT drug-resistant virions proliferate, and this reduces effectiveness of the drug to inhibit virus reproduction

35

The number of resistant virions was sampled after 2, 11, 16 and 20 months and plotted against the concentration of AZT administered Methods Scientific Process

• Question:

• Larder et al (1989)

measured the percentage of resistant virions present in samples from patients. These samples were taken at regular intervals over the AZT treatment. The percent resistance was then plotted against the concentration of AZT typically used to reduce HIV replication.

• Hypothesis: • Prediction: • Methods: • Results: • Discussion: • Conclusions: •

36

18

5/4/2021

FIGURE 1-11

Months after AZT given: 2, 11, 20

Months after AZT given: 1, 11, 16

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

37

AZT treatment was associated with a decrease in the incidence resistance to the drug within the virus population Results

Scientific Process

• Question:

• AZT treatment changes

number of genetic variants for resistance to the drug within the virus population

• Hypothesis: • Prediction: • Methods: • Results:

•

• Discussion: • Conclusions:

38

19

5/4/2021

FIGURE 1-11

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

39

AZT treatment was associated with a decrease in the incidence resistance to the drug within the virus population Scientific Process

Results

• Question:

• AZT treatment changes

• Hypothesis:

number of genetic variants for resistance to the drug within the virus population • AZT resistance arises quickly in about 6 months even in the presence of high doses of the drug

• Prediction: • Methods: • Results: • Discussion: • Conclusions:

40

20

5/4/2021

FIGURE 1-12

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

41

Results of AZT over months of therapy Initially

But after many months…

• Initially the AZT drug was

• But after many months….

effective at a low dose: it reduced the amount of virus and there were negligible amounts of resistant virus.

(describe the AZT resistance in the Figure) ____________________ ____________________ ____________________ ____________________ ____________________

42

21

5/4/2021

Over time the AZT drug resistant virus proliferates, and this reduces effectiveness of the drug to inhibit virus reproduction Scientific Process

• Question: • Hypothesis: • Prediction: • Methods: • Results: • Discussion: • Conclusions:

Discussion & Conclusions • Changes (mutations) in the

enzymes affect their function. The AZT treatment could cause one or more changes, likely in the structure of the reverse transcriptase enzyme, that then increase the ability of the enzyme to function. Over time genetic mutations in the enzyme decrease the effectiveness of AZT

43

FIGURE 1-13

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

44

22

5/4/2021

FIGURE 1-15

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

45

To prevent the effects of evolution of resistance to drugs patients are given a drug cocktail • Highly Active Antiretroviral Therapy (HAART) has been

given to patients since the late 1990s and has dramatically improved the ability of people to live with HIV and maintain low viral counts.

46

23

5/4/2021

FIGURE 1-16

Evolutionary Analysis 5th Ed. Herron and Freeman 2014 Pearson

47

Each drug blocks HIV in a different way • (See link to HIV virus TED talk

https://youtu.be/0TipTogQT3E)

48

24

5/4/2021

Why study evolution? • Because it is a unifying

principle in biology • http://boundless.utoronto

.ca/dev/Campaign%20fo r%20the%20University% 20of%20Toronto%20%20Case%20for%20Su pport.pdf

https://flic.kr/p/qpFFpH

Boundless Inquiry 49

Why study evolutionary biology? • To address a current problem • To prepare for research in evolutionary biology • To make sense of the world we inhabit • What topics would you like to study in evolutionary biology? • _________________________________________________________