HONR 289A The Ecology and Evolutionary Biology of Infectious Disease
Fall 2009
Queen Anne Hall Room 108
Tuesday 3:30 - 6 p.m.
Instructor:
Dr. Benjamin Rosenthal, Henry A. Wallace Beltsville Agriculture Research Center, U.S. Department of Agriculture.
brosenth@umd.edu (forwards to brosenth@gmail.com)
301 504 5408 (office)
Office hours: by prior arrangement on Tuesdays, 2:30-3:30
Course overview:
Certain ecological and evolutionary processes are especially well exemplified by organisms that induce infectious disease
and by their corresponding host responses. The advent of molecular evolutionary genetics has rendered such viral,
bacterial, and parasitic organisms ideal as study subjects because microbial abundance, and their relatively rapid
evolutionary potential, allows us to study (and sometimes even predict) evolutionary trajectories. That should come as
welcome news, given the devastation wrought by the likes of AIDS, malaria, and avian flu.
Population genetics has been termed “the auto mechanics of evolutionary biology” because it studies how standing intraspecific variation becomes converted into distinct biological lineages. We will explore its special contribution to elucidating
the biology of infection. We will also adopt the complementary perspectives of molecular evolution, phylogenetics,
comparative genomics, and epidemiology. Although mastery of any of these disciplines could not be achieved through
such an introductory seminar, students will gain insight into the range of questions that can be posed and tested using
available tools and attainable data.
The objectives of this course are threefold:
1) To gain an appreciation for the diverse methods available to study evolutionary and ecological processes using
increasingly abundant biological data.
2) To understand how these methods may be applied to real problems in infectious disease.
3) To become more critical readers of scientific literature and more precise scientific writers.
Student participation and evaluation:
Over the course of the semester, students will:
Submit 4 Article Overviews (described below; due 4pm Saturday prior to class). (Not individually graded; 5 pts total).
Submit 4 Reaction Papers (described below; due 4pm Saturday prior to class). (15 pts. each; 60 pts. total).
Contribute actively to weekly discussions, serve as the “student facilitator” for one seminar discussion, and keep other
distractions at bay (chats, tweets, posts, texts, or other such distractions erode the seminar environment and are
particularly unfair to those student facilitating class discussion; consequently please ‘unplug during class’. (10 pts).
Prepare a draft term paper for 2 peer reviewers (due 11/10; required, but ungraded).
Provide careful and constructive reviews of two draft term papers (due 11/17; required, but ungraded).
Submit a final term paper (due 11/24) and deliver a 12 minute presentation summarizing the term paper’s themes (on
12/1) (25 pts).
Article Overviews
By semester’s end, you will be expected to submit 4 brief (<1page) Article Overviews.
Each article overview (which could be prepared for an assigned reading, an article cited by an assigned reading, or an
article which has cited an assigned reading) should concisely convey your understand of:
1)
2)
3)
4)
5)
The article’s central question.
Any essential background information motivating that question.
The basic approach taken to addressing the question.
The main findings.
The most important conclusion(s).
A strong ‘article overview’ also includes, where possible, information on the degree of precision, confidence, and/or
uncertainty claimed or acknowledged by the authors, how broadly the results may be fairly generalized, and what lingering
questions or reservations you may have about what was done or what it means.
Article overviews are not individually graded; 5 points are awarded upon completion of four of them.
Article overviews are due, via e-mail, to the instructor by 4pm on the Saturday prior to class.
Reaction Papers
By semester’s end, you will be expected to submit 4 brief (~3 page) reaction papers expressing your observations,
insights, and/or questions about a text (or, preferably, a group of texts). Strong reaction papers do not merely summarize
such texts, but instead discuss your impressions of their content, construction, and conclusions. The strongest reaction
papers integrate information and perspectives from various assigned and unassigned readings, and from class
discussions.
A reaction paper documents your engagement with course materials, allowing you to specify (for yourself, for the reader)
what you find important, persuasive, useful, compelling, intelligible, relevant, applicable, or worthy of further study (or what
fails to do so). Write a good reaction paper and our “student facilitator” will likely seek to emphasize these ideas during
class discussion. Take a position and be prepared to defend it: your favorite study may fall short in other’s eyes. Let’s
find out why, and learn something in the process.
How do you go the extra mile? Follow up on your questions by seeking information from additional sources (the course
reserve materials are a great place to start). Attempt to address, as best you can, points that especially interest or
confuse you. Did doing so resolve your confusion? Reinforce your hunch? Overturn your previous understanding? Take
risks and tackle areas about which you feel uncertain. The best reaction papers document, briefly, a process of discovery
and its results.
By devoting serious attention to your reaction papers, you will:
1- learn about the subject at hand
2- gain experience wrestling with (sometimes challenging) texts
3- improve your skill at succinctly expressing your observations and opinions
4- prepare yourself for classroom discussion
A thoughtful reaction paper may well develop the ideas you seek to explore in greater depth through your term paper.
Each reaction paper is graded on a 15 point scale.
Reaction papers are due, via e-mail, to the instructor by 4pm on the Saturday prior to class.
Course schedule:
Week 1- September 1
Introduction to the content and conduct of this course.
A. Questions.
Why should evolutionary biologists and ecologists pay attention to infectious disease?
Are such diseases still important?
What potential might evolutionary and ecological perspectives contribute to understanding, preventing, or ameliorating
infectious diseases?
What characteristics of infectious diseases are inherently evolutionary or ecological?
B. A taste of what’s to come:
A brief overview of the course content- themes and problems we’ll emphasize.
BREAK
C. Introductions. Do you have specific interests? How might this course fit into your overall educational goals?
D. Overview what successful student participation entails in a seminar.
E. Preview course assignments and opportunities for participation.
F. Overview structures in scientific writing that promote clarity, even when certain terminology or methods may be
unfamiliar. We will pay attention to how papers are presented, with the hope that our own contributions will emulate the
best of these.
G. Overview proper attribution in scientific (indeed in all academic) writing: Generously and accurately acknowledge
whose observations and interpretations lay the foundation for your own understanding of things.
Week 2- September 8
Discuss:
Population dynamics of flaviviruses revealed by molecular phylogenies.
BREAK
Mutational paths to B-lactamase antibiotic resistance.
Phylogeny, demography, epidemiology….convergence?
Assignments:
1. Biology, Evolution, and Infectious Disease: Convergence and Synthesis
Bruce R. Levin, Marc Lipsitch, Sebastian Bonhoeffer
http://www.sciencemag.org.proxy-um.researchport.umd.edu/cgi/content/full/283/5403/806
2. Population dynamics of flaviviruses revealed by molecular phylogenies. Paolo M. De A. Zanotto, Ernest A.
Gould, George F. Gauo, Paul H. Harvey, and Edward C. Holmes. Proc. Natl. Acad. Sci USA Vol. 93 pp 548-553, Jan
1996.
3. Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins Dan Weinreich et al. 2006.
www.sciencemag.org.proxy-um.researchport.umd.edu/cgi/content/abstract/312/5770/111
3. Use Google Scholar or the ISI Web of Knowledge “trace the roots” or “follow the trail” of any of these three articles.
(To sign in to the ISI Web of Knowledge, you’ll need to type in the 14-digit number that appears above the barcode on the
back of your University ID).
http://portal.isiknowledge.com.proxy-um.researchport.umd.edu/portal.cgi?DestApp=WOS&Func=Frame
4. This is your first opportunity to write a ‘reaction paper’, which should attempt to tie together what you learned from an
assigned reading and one of its antecedents or successors. It will be interesting to discuss the diverse directions this
takes the class. You may also elect to write an ‘article overiew’ which succinctly distills the content of a particular
reading.
5. On October 13, we will discuss Alfred Crosby’s Ecological Imperialism: The Biological Expansion of Europe, 900-1900.
Get your copy now, either at the library, or online…. Amazon.com, for instance, has plenty of used and new copies for $812 plus shipping.
Week 3- September 15
A. Round robin on the biology and epidemiology of several important diseases.
Who read about Malaria, and what did you learn? How is it transmitted? Where? To whom? Under what
circumstances?
Who read about Toxoplasmosis, and what did you learn?
Who read about AIDS, and what did you learn?
Who read about Tuberculosis, and what did you learn?
Who read about Influenza A virus, and what did you learn?
Who read about Cholera, and what did you learn?
Who read about Human papillomavirus, and what did you learn?
BREAK
Report from the field: summarize, in just a few minutes, the article you found. Give us a few words of background, the
paper’s objectives, its methods, findings, and interpretation. Would you choose to pursue additional information about this
topic, or recommend it to others? Why or why not?
Assignments:
1. Read something about the basic biology and transmission of three of the following diseases: Malaria, Toxoplasmosis,
AIDS, Tuberculosis, Influenza A virus, Cholera, Human papillomavirus.
Books, review articles, research papers, websites provide such information and serve as portals to additional resources.
(Note: the quality of any information source must be assessed, and this is especially so for information on the web, which
may or may not have undergone critical peer review. For this particular assignment, cdc.gov provides a good starting
point).
2. Many people now study how hosts and pathogens interact, how microbes evolve, the implications for such evolution to
the spectrum of disease that they cause, the continued efficacy of drugs deployed against them, or the challenge of
developing vaccines. Others investigate factors that naturally promote (or suppress) disease transmission or the results
of interventions intended to improve public health. Your mission: “go out” and find a study, relating to one or more of
these course themes, and digest as much of it as you can. Summarize the background, purpose, observations, and
conclusions of the study. Weigh in on A) how effectively you believe those to have been explained and B) any ideas it
brings to mind that you think merit follow up. You need not understand every technicality embodied within the paper.
Make your best effort to grasp the most important aspects of the findings and conclusions being advanced, understanding
that you have not necessarily been exposed to all the background that would be necessary to comprehensively assess its
merits.
3. If you haven’t yet gotten your copy of Crosby’s Ecological Imperialism, do so.
Week 4 September 22
Discuss Mechanisms of Influenza A evolution.
Influenza- viral reassortment, antigenic drift, and successive strain replacement.
BREAK
Expert panel: is UMD adequately prepared?
Assignments:
1. Read an introduction about antigentic shift and antigenic drift in influenza viruses at:
http://www.cdc.gov/flu/about/fluviruses.htm#how
2. Predicting the evolution of Influenza A.
3. Ecological and immunological determinants of influenza evolution.
4. Large-Scale Sequence Analysis of Avian Influenza Isolates
5. Find a scientific article, and a press account, addressing a question you have about H1N1 flu.
6. Read the University of Maryland’s emergency preparedness plan concerning H1N1.
http://www.umd.edu/umnews/h1n1fall09.cfm
Week 5- September 29
AIDS, the zoonoses. Understanding the origins of HIV and modeling the determinants to its management or spread.
BREAK
The evolutionary genetics of resistance to HIV
Readings:
1. Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1
2. Limitations of a Molecular Clock Applied to Considerations of the Origin of HIV-1
3. The Geographic Spread of the CCR5 delta HIV-Resistance Allele.
4. A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1
www.sciencemag.org.proxy-um.researchport.umd.edu/cgi/content/abstract/317/5840/944
Week 6- October 6
Malaria’s Eve:
Evidence from parasite population genetics
BREAK
The age of human adaptations to malaria
Readings:
1. Malaria’s Eve: Evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum
by Rich et al.
2. Recent Origin of Plasmodium falciparum from a Single Progenitor by Volkman et al.
3. Haplotype Diversity and Linkage disequilibrium at Human G6PD: Recent Origins of Alleles that confer malarial
resistance.
Has anything else been written on the subject recently?
Week 7- October 13
Discuss Ecological Imperialism and its perspective on past pandemics.
BREAK
Continue discussion…and its relevancy to ongoing and feared future epidemics.
1. Read Ecological Imperialism: The Biological Expansion of Europe by Alfred W. Crosby.
2. Read Evolution, consequences and future of plant and animal domestication by Jared Diamond
Nature 418, 700-707 (8 August 2002)
www.nature.com/nature/journal/v418/n6898/abs/nature01019.html
3. Do any diseases currently rival those described above in their social impact? Are there any you fear may? Find
something to read that discusses an ongoing or anticipated scourge, and relate it to what you have read about past
pandemics.
Week 8- October 20
Clonality- a concept borrowed from bacteriology.
Asexual perpetuation of Toxoplasma gondii?
Grigg et al and the clonal model for Toxoplasma gondii.
BREAK
Is it more complicated than that?
Lehmann et al.
Readings:
1. Read enough of “How clonal are bacteria?” of John Maynard Smith et al so that you think you understand what is being
conveyed by figure 1. Don’t feel compelled to review all of the data in the paper. Save time for the following three papers
on Toxoplasma gondii (which is not bacterial).
2. Success and Virulence in Toxoplasma as the Result of Sexual Recombination Between
Two Distinct Ancestries Grigg et al.
3. Globalization and the population structure of Toxoplasma gondii by Lehmann et al.
4. Recent expansion of Toxoplasma gondii through enhanced oral transmission by Su et al.
Has anything else been written on the subject recently?
Week 9- October 27
The Evolution of virulence: evidence from ‘natural experiments’
BREAK
The evolution of virulence: evidence from controlled experiments.
Readings:
1. Readings:
Population structure and the evolution of virulence in nematode parasites of fig wasps
Crossing the line: Selection and Evolution of Virulence Traits
Convergence of the secretory pathways for cholera toxin and the filamentous phage ctx
Experimental evolution of Parasites
Week 10- November 3
Variable surface antigens: moving targets
BREAK
Immunodominant antigens: deceptive targets?
Assignments:
1. Readings:
HIV-1 Evolution and Disease Progression
Var genes
Deceptive imprinting
2. A fully referenced draft of your term paper is due in one week, so set November 3 as a goal for having a strong outline
put together (this is not an assignment to be turned in, but rather a bit of scheduling advice).
Week 11- November 10
Elucidating other facets of evolutionary biology using the variability of pathogens and their hosts.
Co-phylogeny and relative evolutionary rates
BREAK
Does the number of ancestral alleles tell us something about the number of ancestors we’ve had?
Assigments:
1. Read Disparate rates of Molecular Evolution in Gophers and their chewing lice; Myth of Eve
2. Bring three copies of your draft term paper (one for each of two peer reviewers, and one for me) at the beginning of
class, November 10
.
NUMBER the lines of your text to ease the reviewer’s need to direct comments and suggestions to specific portions of
your text. In Microsoft Word, this can be accomplished as follows:
1.
2.
3.
4.
On the File menu, click Page Setup, and then click the Layout tab.
In the Apply to box, click Whole document.
Click Line Numbers.
Select the Add line numbering check box, and then select the options you want.
See the next week to understand what your reviewer will be looking for.
Week 12- November 17
Basic epidemiological models- and its relationship to ecology more generally.
BREAK
Ecology of pathogen interaction: TB and HIV.
Transmission parameters and the political forces that shape them: cost-effectiveness in TB control.
Assignments:
1. Read the Wikipedia page providing an overview of Mathematical modeling in epidemiology:
http://en.wikipedia.org/wiki/Mathematical_modelling_in_epidemiology
You will not be quizzed on the math here. But make an effort to see where they are trying to go with this. Play with some
scenarios and see if the relationships make sense to you.
2. Read and come ready to discuss “Antiretroviral Drugs for Tuberculosis Control in the Age of HIV/AIDS” by Williams and
Dye, a paper that uses such a perspective to forecast the effects of particular health policies.
3. Read and come ready to discuss “Limited good and limited vision: multidrug-resistant Tuberculosis and global health
policy” by Kim et al.
4. Perform a thorough review of each of the two projects you have been provided.
Your review should address both the concepts underlying the paper, as well as the mechanics of its execution.
Are the issues to be discussed clearly delineated?
What are the most interesting issues being raised in the paper?
Can you state the central objective or theme of the paper? Has the author done so in a concise and interesting way?
Do these objectives seem achievable within the scope of such a paper? You may suggest other vantage points to
broaden the paper or, perhaps, recommend those areas deserving most emphasis if the study seems overly diffuse.
Is sufficient background information provided in the introduction, and is it thoroughly referenced?
Is subsequent information presented in a logical order?
What parts are written with greatest clarity? Are there rough spots that seem vague, awkwardly worded, or repetitive?
Does each paragraph develop a particular idea or point?
Do any issues merit further attention or clarification?
Do any inaccuracies require correction?
Are points of conjecture qualified as such?
Is the writing precise? Does it define specialized terms? Are grammatical or spelling errors evident?
Do its conclusions seem justified?
Was it a satisfying what did you learn?
Having read the paper, do you believe the title succinctly conveys the essence of the matter? (You may suggest
alternatives).
DOES THE PAPER GENEROUSLY AND ACCURATELY ACKNOWLEDGE whose observations and interpretations lay
the foundation for each idea? DRAFTS LACKING literature citations throughout the text and a bibliography will be
returned (after instructor approval) without comment (ouch! Please do not make this mistake).
Reviewers should point out any places where he or she cannot easily discern the provenance of an idea or phrase, or
where the text could reasonably be interpreted as claiming for its author credit for ideas or language rightfully attributed to
others. In other words, does the text consistently explain who helped develop the ideas and observations that support (or
refute) ideas discussed in the paper?
Is the reference section, itself, complete and consistent?
Be fair….and as constructive as possible. Remember that there are diverse ways of effectively presenting ideas (not all
conforming to your own preferences). Provide the author concrete feedback for strengthening their work. The author will
be looking to you for advice they can actually USE in the remaining time- reviews recommending that the entire idea be
scrapped are not likely to be viewed with sympathy!
Remember- peer review’s purpose is to help safeguard the quality and integrity of published work (such review
determines whether and where a given paper will be published). Publishers and editors depend on this process to ensure
that the content of their text is sound.
Authors, themselves, are also protected in the process…because the need to satisfy knowledgeable and careful
reviewers improves the writing upon which an author’s reputation will be based. As a reviewer in our course, you are
providing an essential service to the author by offering constructive advice.
Week 13- November 24
Ecosystem energetic implications of parasite and free-living biomass in three estuaries
Assignments:
1. Complete your term paper. Give serious consideration to your reviewer’s suggestions for strengthening its content
and/or organization. Due at the beginning of class on November 24
2. Please read Ecosystem energetic implications of parasite and free-living biomass in three estuaries
Week 14- December 1 Student Presentations (1)
Assignments:
1. Put together an oral presentation of your final project (10-12-minutes, plus 3 minutes for questions; Illustrating your talk
generally helps….you may use the chalk board. If you elect to use Power Point, I will need your slides (generally 4-5
slides suffices) by 8:30 AM December 1st so that they can all be loaded and ready to go with minimal delay in the
transition between talks.
Outline your interests, what you set about to learn, what you found, what you concluded, and perhaps what you see as
interesting future work. PRACTICE your talk in front of a willing friend to see how long it really takes, what came off
clearly, and what you need to better explain or illustrate. Practice it again (preferably on a new “victim”) to see how well
you’ve smoothed the rough edges. It might seem awkward to ask for 15 minutes of someone else’s time, but such
practice will build your confidence and help you accurately assess your presentation’s length.
2. Course evaluation
Your participation in the evaluation of courses through CourseEvalUM is a responsibility you hold as a student member of
our academic community.
Your feedback is confidential and important to the improvement of teaching and learning at the University as well as to the
tenure and promotion process. CourseEvalUM will be open for you to complete your evaluations for fall semester courses
between Tuesday, December 1 and Sunday, December 13. You can go directly to the website
(www.courseevalum.umd.edu)to complete your evaluations starting December 1. By completing all of your evaluations
each semester, you will have the privilege of accessing the summary reports for thousands of courses online at Testudo.
Week 15- December 8 Wrap up
Course conclusion.
Recommended resources at McKeldin Library
Plagues and peoples
William H. McNeill.
Anchor Press, 1976.
Guns, germs, and steel : the fates of human societies
Jared Diamond. W.W. Norton, c1997.
Ecological imperialism : the biological expansion of Europe, 900-1900
Alfred W.Crosby. Cambridge University Press, 2004.
Principles of population genetics
Daniel L. Hartl, Andrew G. Clark.
Sinauer Associates, c1997.
An illustrated guide to theoretical Ecology
Ted J. Case. Oxford University Press, 2000.
Molecular evolution : a phylogenetic approach
Roderic D.M. Page and Edward C. Holmes. Blackwell Science, 1998.
Infectious diseases of humans : dynamics and control
Roy M. Anderson and Robert M. May. Oxford University Press, 1991.
Evolution of infectious disease
Paul W. Ewald. Oxford University Press, 1994.
Immunology and evolution of infectious disease
Steven A. Frank. Princeton University Press, c2002.
Essentials of human parasitology
Judith S. Heelan, Frances W. Ingersoll. Delmar, c2002.
Evolutionary genetics : from molecules to morphology
edited by R.S. Singh and C.B. Krimbas. Cambridge University Press, 2000.
Fundamentals of molecular evolution
Dan Graur, Wen-Hsiung Li. Sinauer Associates, c2000.
New uses for new phylogenies
edited by Paul H. Harvey Oxford University Press, 1996.
• Academic Accommodations: If you have a documented disability, you should contact Disability Support Services 0126
Shoemaker Hall. Each semester students with documented disabilities should apply to DSS for accommodation request
forms which you can provide to your professors as proof of your eligibility for accommodations. The rules for eligibility and
the types of accommodations a student may request can be reviewed on the DSS web site at
http://www.counseling.umd.edu/DSS/receiving_serv.html.
• Religious Observances: The University System of Maryland policy provides that students should not be penalized
because of observances of their religious beliefs, students shall be given an opportunity, whenever feasible, to make up
within a reasonable time any academic assignment that is missed due to individual participation in religious observances.
It is the responsibility of the student to inform the instructor of any intended absences for religious observances in
advance. Notice should be provided as soon as possible but no later than the end of the schedule adjustment period.
Faculty should further remind students that prior notification is especially important in connection with final exams, since
failure to reschedule a final exam before the conclusion of the final examination period may result in loss of credits during
the semester. The problem is especially likely to arise when final exams are scheduled on Saturdays.
Academic Integrity & the Honors College
The University is an academic community. Its fundamental purpose is the pursuit of knowledge. Like all other
communities, the University can function properly only if its members adhere to clearly established goals and values.
Essential to the fundamental purpose of the University is the commitment to the principles of truth and academic honesty.
Accordingly, the Code of Academic Integrity is designed to ensure that the principle of academic honesty is upheld. While
all members of the University share this responsibility, The Code of Academic Integrity is designed so that special
responsibility for upholding the principle of academic honesty lies with the students. (The University of Maryland Student
Honor Council)
All University of Maryland students are asked to write and sign the following Honor Pledge to all submitted assignments
and exams:
I pledge on my honor that I have not given or received any unauthorized assistance on this assignment/examination.
The University of Maryland honor system is fully described in the Code of Academic Integrity. Please read:
www.studenthonorcouncil.umd.edu/code.html. The Code is administered by an all-student Honor Council. The student
Honor Council office is located in room 2118 Mitchell Building and can be reached at 301-314-8204.
The Honors College works to enrich its community life by promoting an atmosphere of honesty, trust, and mutual
responsibility. In the event that a Honors College student is found responsible for a violation of the Code of Academic
Integrity by the Student Honor Council, he or she will be dismissed from the Honors College for the semester in which the
violation took place and for all subsequent semesters in which the student is enrolled as an undergraduate at Maryland.