The plan for the last three lectures of the semester:

1
The plan for the last three lectures of the
semester ? - Monday Dec. 5 - The Red Queen
Hypothesis Microevolution in Pathogenic
Microorganisms ? Wednesday Dec. 7 - Dr.
Berlochers research (Apples, Pests, and
Evolution) ? Friday Dec. 9 - Careers in
Integrative Biology, Dr. Berlochers evaluations
2
Hughes Undergraduate Research Fellowships
Summer Living-Learning Community and Research
Program June 4 - August 6, 2005

• Fellowship Award
• 2,600 stipend
• Housing and dinner meals at Illini Tower
• Tuition waiver for 4-5 hours of graded
  research/independent study credit
• Application Review Process
• Program information and application
  www.life.uiuc.edu/hughes/hurf/
• Turn in completed application by January 25,
  2006
• Applications will be evaluated based on academic
  record and personal statement
• Contact Information
• Nikki Lowery, HURF Program Manager
• E-mail hurf_at_life.uiuc.edu
• Office 428 Natural History Building

• The Program
• Research experience for undergraduates
• Workshops, seminars field trips
• Living-learning community of like-minded students
• Academic year continuation program
• Eligibility
• Minimum Overall GPA of 2.75
• Minimum math science GPA of 3.00
• UIUC freshman, sophomore, or junior in
• Animal Sciences
• Bioengineering
• Biology (IB, MCB, unassigned)
• Chemistry
• Crop Sciences
• NRES

3
IB 150 Final Exam 800-1100 AM, Thursday,
December 15 ? The final exam will have about 100
questions. About 50 will come from material
covered since the last hour exam, including
Integrative Topics lectures. The rest will come
from the earlier part of the course. ? We will
take a few questions directly from the two
previous exams. ? Room and other information
later this week.
4
Final exam advice If you have questions, go
talk to your TA or to me! Dont wait till the
last possible minute to get your questions
answered! I will be holding my usual office
hours (2 - 4 PM) Tuesdays and Thursdays this week
and as much of next week as I can manage. I will
also be answering the Web Crossing page.
5
Before going on, I want to say a few words about
our new IB Honors Biology program. The original
Honors Biology program did not survive the split
of the School of Life Sciences into two schools,
but both IB and MCB have new Honors programs
starting. The IB program is modeled very closely
after the original Honors program, so let me tell
you a bit about that.
6
Honors Biology (1962 - 2005) - Three core
courses, The Cell, The Organism, and The
Population taken by all students. Core courses
taught by professors and dedicated TAs
professors attend labs. - Lab intensive courses.
Dedicated lab space. Students had keys to the
labs, and could use the labs at any time. For
The Population, serious field work, one overnight
trip. - Writing-intensive courses. Essay exams,
lab reports in the form of research papers. Comp
II credit for The Cell. - Lots of additional
course requirements. Statistics. Majors physics.
72 hours required courses. - Admission by
interview conducted by a professor and two
current students. 30 students in each year.
7
Honors Biology (1962 - 2005) Outstanding
biologists.
Matthew "Max" Krummel, Assistant Professor of
Pathology, Department of Pathology, University of
California at San Francisco, Honors Biology and
Biochemistry 1989
Douglas Melton, Howard Hughes Medical
Institute Department of Molecular and Cellular
Biology Harvard University, Honors Biology 1975
Rebecca D. Klaper, Shaw Assistant Scientist,
Great Lakes WATER Institute, University of
Wisconsin-Milwaukee, Honors Biology 1992
Larry A Nielsen, Provost, North Carolina State,
Honors Biology 1970
8
(No Transcript)
9
(No Transcript)
10
(No Transcript)
11
Details of the new IB Honors Program are
available on the IB web site, and I will be
talking to some labs this week. We also have a
brochure. Talk to us if you are interested!
Asistant Professor Charles Whitfield, teaching
the Cell course in the new IB program.
12
Integrative Topic Lecture III (Berlocher) The
Red Queen Hypothesis Microevolution in
Pathogenic Microorganisms
13
Lecture 39 - The Red Queen Hypothesis
Microevolution in Pathogenic Microorganisms
Readings none.
Microorganisms and microevolution. The Red
Queen Hypothesis. Reasons for rapid virus
evolution. high mutation rate fast
generations. Things to remember from early in
course. mutations occur in tree-like patterns
phyogentic tree allele frequency change natural
selection genetic drift.
A little bit about the human immune
system. antigen antibody 2 week antibody
development antibody memory Microevolution in
influenza virus antigen drift antigen shift
1918 pandemic, vaccine development
Microevolution in HIV molecular clock drug
resistance natural immunity
14
Disease-causing microorganisms (protozoa,
bacteria, and viruses) and their hosts are
engaged in a continual, biochemical arms race
with humans. Viruses, for example, continually
evolve new genetic strains, and the human immune
system responds. Humans also have some capacity
for microevolutionary response.
15
L. van Valens Red Queen Hypothesis (modified
version) rapid adaptation of parasites to hosts
is continually occurring.
...in this place it takes all the running you
can do, to keep in the same place. Through the
Looking Glass, Lewis Carol
16
Why is there such rapid virus evolution? Viruses,
especially RNA viruses (which use RNA instead of
DNA for genes) have 1) an extraordinarily high
rate of mutation (as large as a 10-4 probability
of a base not being replicated correctly per
generation) and 2) extremely short generation
times (for example, 1.2 days for HIV
virus). Plus, there is a lot of drift and
selection...
17
Generation
..AATCGT..
1
2
..AATCCT..
..AATCGT..
3
..AATCGT..
..AATCCT..
4
..CATCCT..
..AATCGT..
..ATTCGT..
..AATCCT..
Mutation adds new sequences (alleles) of genes
in a tree-like pattern
Normal replication
Abnormal replication - mutation
18
We can reconstruct the history of mutations using
a phylogenetic tree graph (parsimony tree). This
is actually an estimated reconstruction of the
phylogeny, but for of microbial evolution over
time spans of a only decade or two, estimation is
highly accurate.
19
1.0
Frequency of an allele (which could be a new
mutation or part of standing variation)
0.0
time
Alleles can be lost - become extinct
Alleles can be increase in frequency due to drift
or natural selection
20
The other player in this story is the human
immune system. It is capable of making
antibodies to various chemicals that are
introduced into the body. Such chemicals are
called antigens. Viral coat proteins are
important antigens. A key fact is that it takes
about 2 weeks for humans to make a new antibody.
Once a human has made an antibody, it can be made
more rapidly the second time (antibody memory).
21
Two viruses

• Influenza virus
• HIV

22
The influenza virus

• Causes the flu symptoms we all know, but is not
  the only virus to cause runny noses, fevers, and
  all the rest of the symptoms.
• Is an RNA virus that replicates itself in animal
  cells. Like all viruses, it is a complete
  parasite, and cannot replicate unaided.
• Can be defeated by the human immune system, but
  it takes 2 weeks to mount a complete defense.

23
The influenza virus in the electron microscope.
Note the projections on the outside, and in the
photo on the left, indications of structures
inside the capsule.
24
The projections are two types of proteins,
haemaglutinin and neuramindase, which are
antigens - molecular sites to which the human
body can make antibodies.
25
Influenza virus reproduction in cells of the
tissues lining the respiratory system
The viral life cycle occurs in human cells, and
uses the human nucleus and translation mechanism
to replicate itself.
26
Influenza coat protein evolution The human
immune system usually (given 2 weeks) destroys a
virus infection (but usually not before
transmitting it to another person). Eventually,
almost all of the people who get the virus become
immune and second infections fail. But the
influenza virus is constantly giving rise to new
mutations, with different amino acid sequences in
coat proteins. Such a new sequence (surviving in
a few people) can re-infect many people the next
flu season because antibodies cannot be made
rapidly against it. Thus there is continual
evolution of new viral sequences. This process
is called, confusingly, antigen drift. But
this process is not caused primarily by genetic
drift, but by selection.
27
A really remarkable tree Haemaglutinin gene
evolution in influenza type A strains from 1985 -
1996. This represents 1348 base
substitutions! Where are the side
branches? Evidence for strong selection.
From Bush et al. 1999. Positive Selection on the
H3 Hemagglutinin Gene of Human Influenza Virus A.
Mol. Biol. Evol. 1614571465. 1999
In medical terminology this is called antigen
drift, but it is primarily selection, not
genetic drift.
28
But there is also a process of antigen shift,
which comes about from reshuffling of the
genome of the influenza virus. Such a shift has
been responsible for some of the major flu
outbreaks in the past. However, the killer 1918
flu actually seemed to be a pure avian flu.
29
Influenza A has a large number of subtypes that
infect birds and pigs as well as humans.
Some of these types can infect humans (avian
flues and swine flues). If a person is
infected with human type, and a pig or bird type,
some cells can be infected with both types at the
same time, so that a new type with alleles from
both types can be created. Such a flu can be a
surprise to the human immune system.
30
Influenza A subtypes (not all shown in this tree
of haemaglutinin sequences) which infect birds
and pigs as well as humans. Note the arrow
showing the position of the 1918 sequences.
However, the 1918 sequences have avian features
as well.
31
Every year, researchers at the Centers for
Disease Control and elsewhere try to guess what
next years flu strain will be, so that vaccines
can be made. Most of the searching is done in
China, where there is a very high human
population density, and many people still live in
close proximity to pigs as well as ducks and
other birds. Three Chinese strains are chosen
and used to make the next years vaccines. This
process involves growing the flu strains in
millions of eggs!
32
(No Transcript)
33
The other case for todays lecture involves the
HIV (human immuodeficiency virus) that causes
AIDS. Briefly, this is a retrovirus (an RNA
virus that uses host DNA to reproduce itself)
that is particularly devastating because it
directly attacks the human immune system by
destroying certain types of lymphocytes. However,
the human body still produces some antibodies
against HIV. This antibody production drives some
remarkable molecular evolution.
34
(No Transcript)
35
A well-studied series of infections in Sweden
provides a natural known phylogeny for a series
of HIV populations.
36
An HIV molecular clock
Sequences from 2 people with more than 20 years
separation.
1) A fantastic rate of change - even in a single
person. 2) A molecular clock - a roughly linear
rate of molecular evolution.
Sequence divergence (bases different/total bases
compared) for V3 region of coat glycoprotein.
Sequences from 2 people with less than 1 year
separation.
37
Figure 25.17 Dating the origin of HIV-1 M with a
molecular clock
38
A rather amazing fact A tiny fraction of humans
are resistant (not really immune) to HIV due to
a mutation in a human cell membrane protein that
HIV needs to start the process of entering a
T-cell.
39
Thus, humans and our diseases are engaged in a
perpetual, deadly game of molecular warfare.
This game is only understandable in the language
of evolutionary biology. Or maybe Alice...
40
Lecture 39 - The Red Queen Hypothesis
Microevolution in Pathogenic Microorganisms
Readings none.
Microorganisms and microevolution. The Red
Queen Hypothesis. Reasons for rapid virus
evolution. high mutation rate fast
generations. Things to remember from early in
course. mutations occur in tree-like patterns
phyogentic tree allele frequency change natural
selection genetic drift.
A little bit about the human immune
system. antigen antibody 2 week antibody
development antibody memory Microevolution in
influenza virus antigen drift antigen shift
1918 pandemic, vaccine development
Microevolution in HIV molecular clock drug
resistance natural immunity