Transcript evolution? - Ecology and Evolutionary Biology

ECOL/MCB/CPH/VSC 409/509
Evolution of Infectious Disease
Dr. Michael Worobey
BSW 324
[email protected]
626-3456
Goals of the course
•Learn some fundamental evolutionary theory as it
relates to infectious disease
•Learn about some of the evolutionary tools that are
used to understand infectious disease, such as
molecular phylogenetics
•Acquire cutting-edge knowledge about some of the
most important human infectious diseases, like HIV
•Learn how to read and critique the primary scientific
literature, and interpret stories in the popular media
The transmissible agent causing canine transmissible venereal tumor
(CTVT) is thought to be the tumor cell itself. To test this hypothesis, we
analyzed genetic markers including major histocompatibility (MHC)
genes, microsatellites, and mitochondrial DNA (mtDNA) in naturally
occurring tumors and matched blood samples. In each case, the tumor is
genetically distinct from its host. Moreover, tumors collected from 40 dogs
in 5 continents are derived from a single neoplastic clone that has
diverged into two subclades. Phylogenetic analyses indicate that CTVT
most likely originated from a wolf or an East Asian breed of dog between
200 and 2500 years ago. Although CTVT is highly aneuploid, it has a
remarkably stable genotype. During progressive growth, CTVT
downmodulates MHC antigen expression. Our findings have implications
for understanding genome instability in cancer, natural transplantation of
allografts, and the capacity of a somatic cell to evolve into a transmissible
parasite.
Questions raised?
SOME REASONS FOR STUDYING
THE EVOLUTION OF INFECTIOUS
DISEASE
1. We all have a vested interest since
we’re susceptible and infectious
disease touches everyone’s life
- HIV, flu, colds, antibiotics, immune
system
SOME REASONS FOR STUDYING
THE EVOLUTION OF INFECTIOUS
DISEASE
2. It’s where the data are.
- There is a huge amount of sequence
data from medically important
microbes
- Viruses and bacteria were the first
sequenced genomes, beguilingly
simple
SOME REASONS FOR STUDYING
THE EVOLUTION OF INFECTIOUS
DISEASE
3. “infectious disease” covers a sizable
fraction of the diversity of life on Earth
"So, the naturalists observe, the flea,
Hath smaller fleas that on him prey;
And these have smaller still to bite 'em;
And so proceed, ad infinitum"
--Jonathan Swift
SOME REASONS FOR STUDYING
THE EVOLUTION OF INFECTIOUS
DISEASE
4. You can often see evolution’s fingerprint
more clearly in pathogens…
-microbes evolve in “real time”, fast-paced
-vertebrate immune system as an evolutionary
response
-positive selection, amino acid by amino acid
SOME REASONS FOR STUDYING
THE EVOLUTION OF INFECTIOUS
DISEASE
5. Infectious disease may help explain
some “evolutionary scandals” such as
the ubiquity of sex
“Parasite Red Queen”
SOME REASONS FOR STUDYING
THE EVOLUTION OF INFECTIOUS
DISEASE
6. We’re all shaped to a great extent by
our long arms race with infectious
disease agents
-examples?
SOME REASONS FOR STUDYING
THE EVOLUTION OF INFECTIOUS
DISEASE
7. Gives us a sort of crystal ball to try to
predict the future.
-Will HIV evolve toward low virulence?
-What will next year’s flu strain look
like?
-How long will current malaria drugs
work?
Topics covered:
EVOLUTION:
• Brief history of evolutionary theory
• The concept of natural selection
• Some evolutionary themes that are
relevant across many different
perspectives, including those involving
infectious disease:
1.
2.
3.
4.
Adaptation
Conflicts
Trade-offs
Constraints
What’s the role of parasites in
the biological big picture?
•Sex is costly, not to mention complicated and
dangerous
•Searching for mates takes time and energy, and has
risks (?)
•Potential mates may demand additional exertion or
investment before mating
•After all that, mating might prove to be infertile
•Why go to all the trouble?
In a population conforming to JMS’s assumptions,
asexual females produce twice as many grandchildren
as sexuals
Case study I: Parasites and the advantage of sex
Which reproductive mode is better: sexual or asexual?
Null model: (what a null model?)
1. A female’s reproductive mode does not affect the
number of offspring she can make
2. A female’s reproductive mode does not affect the
probability that her offspring will survive
(John Maynard Smith, 1978)
QuickTime™ and a
TIF F (Uncompressed) decompressor
are needed to see this picture.
The central role of parasites in evolution
How do humans and other animals
protect themselves against
pathogens?
Brief history of
immunology
•
•
•
Relatively new
science; origin
usually attributed to
Edward Jenner, but
has deep roots in
folk medicine
Jenner discovered
in 1796 that cowpox
(vaccinia) induced
protection against
smallpox
Jenner called his
procedure
“vaccination”
Brief history of
immunology
•
•
It took almost two centuries for smallpox vaccination to
become universal
Vaccination enabled the WHO to announce in 1979 that
smallpox had been eradicated, arguably the greatest
triumph in modern medicine.
Figure 1-15
How does the immune system work?
How do diseases evolve in response to it?
What are the consequences?
MHC class I molecule presenting an
epitope
Figure 3-23
When and how did our
immune defenses come to
be?
Evolution of the immune
system
•
•
•
The most ancient
immune defenses lie
within the innate
immune system
Drosophila spp. Have
well developed innate
immune system
The first defense
molecules in
evolutionary terms were
probably antimicrobial
peptides, produced by
plants and animals
What sorts of organisms
make us sick?
The three domains of life
BACTERIA
ARCHEA
*
0.1 CHANGES/SITE
EUCARYA
Major killers: malaria
•
Forty-one percent of the world's population live in areas
where malaria is transmitted (e.g., parts of Africa, Asia, the
Middle East, Central and South America, Hispaniola, and
Oceania).
•
* An estimated 700,000-2.7 million persons die of malaria
each year, 75% of them African children.
•
* In areas of Africa with high malaria transmission, an
estimated 990,000 people died of malaria in 1995 – over
2700 deaths per day, or 2 deaths per minute.
Global impact of HIV/AIDS
Are parasites always “bad”?
evolutionary innovations
through symbiosis: examples
• Eukaryotic cell (mitochondria)
• Photosynthesis in eukaryotes (plastids)
• Colonization of land by plants
(mycorrhizae)
• Nitrogen fixation by plants (rhizobia)
• Animal life at deep sea vents
(chemoautotrophic life systems)
• Use of many nutrient-limited niches by
animal lineages
Why do hosts and symbionts cooperate
so often?
• Persistent association allows both to increase their persistence
and replication.
– Coinheritance
– Long-term infection
• Intimate metabolic exchange generating immediate beneficial
feedback
late embryos
maternal bacteriocytes
containing symbionts
early embryos with
symbionts visible
1 mm
J. Sandström
host aphid gene phylogeny
Buchnera gene phylogeny
Aphididae
Uroleucon & relatives
Pemphigus betae
Ac yrthosi phon pi sum
origin of
symbiosis
Sc hl ec tendalia c hinensi s
Mac ros iphum ros ae
Uroleuc on eri geronense
Mel aphis rhois
Uroleuc on caligatum
Chaitophorus viminalis
Uroleuc on rurale
Uroleuc on helianthic ol a
Mindarus ki ns eyi
Uroleuc on jaceicola
Uroleuc on sonc hi
Uroleuc on ob sc urum
Uroleuc on rapunculoides
Ac yrthosi phon pi sum
Uroleuc on sonc hi
Mac ros iphum ros ae
Myzus pers ic ae
colonization
of Asteraceae
<20 Mya
Uroleuc on solidaginis
Uroleuc on jaceae
Uroleuc on aeneum
Rhopalosi phum padi
ancestor of
extant aphids
100-200 Mya
Uroleuc on rudbeck iae
Sc hi zaphis grami num
Rhopalosi phum mai dis
Uroleuc on as tronomus
Uroleuc on ambrosi ae
->Strict vertical transmission since ancient infection of ancestral host
Use of modified bacteria to manipulate natural
communities to prevent disease states?
Streptococcus mutans--recombinant
does NOT make lactic acid (cavity-causing agent)
makes toxin against competing (cavity inducing) strains
persists for life and prevents cavities?
Why are some parasites so
virulent compared with
others?
The Evolution & Ecology of Infectious
Disease
Why are some species pathogenic to humans
while other (closely-related) species are not?
This question can approached from two directions:
1.From the point of view of the host. What specific defense
mechanisms of the host allow it to suppress infection (entry,
attachment, invasion, replication) by certain agents and not
others?
2.From the point of view of the pathogen. What are the
differences between the agents that cause disease and those
that do not?
Inferrring lateral gene transfer (LGT) from
sequence heterogeneity along the chromosome
Neisseria meningitidis, 52% G+C
(from Tettelin et al. 2000. Science)
Yersinia pestis: Rapid evolution of an enteric pathogen
Three (of the 11) species of Yersinia are pathogenic to
humans:
Y. enterocolitica & Y. pseudotuberculosis cause
gastroenteritis, whereas Y. pestis is the causative
agent of the bubonic plague.
Three known plague pandemics:
Justinian, 541-767; Black Death, 1346-1800s; Modern 1894-present
The classis example: Myxoma virus
•
•
•
•
•
•
Pox virus introduced into Australia to control
European rabbit populations
Vectored by mosquitos and fleas, skin lesions
Initially the virus was extremely virulent (99%)
mortality
A sharp drop in virulence was initially observed
However, the circulating virus remained much more
virulent than lab strains
Positive coupling between transmission and virusinduced mortality
1. Think globally, act locally.
2. Given enough time a state of peaceful coexistence
eventually becomes established between any host and
parasite.
-Rene Dubos
Quic kT i me™ and a
T IFF (Unc ompres s ed) dec ompres s or
are needed t o s ee thi s pi c ture.
Trade-offs
How do our immune defenses
shape the evolution of
pathogens?
natural selection
How do pathogens
circumvent our defenses?
•The surface of a
trypanosome is
covered with variantspecific glycoprotein
(VSG)
•There are about 1000
different VSG genes
•Upon initial
infection, antibodies
are raised against the
VSG initially
expressed
• Initial infection by herpes
simplex virus in the skin is cleared
Figure
11-4
by an effective immune response
•But residual infection persists in
sensory neurons
•When the virus is reactivated, the
skin is re-infected. This can be
repeated endlessly
Figure 11-5 part 3 of 3
How have pathogens shaped
human (and deeper)
evolution?
How has disease impacted human evolution?
What techniques are used to
test evolutionary hypotheses
regarding infectious disease?
Molecular phylogenetics fundamentals
All of life is related by common ancestry. Recovering this pattern, the "Tree of Life",
is one of the primary goals of evolutionary biology. Even at the population
level, the phylogenetic tree is indispensable as a tool for estimating
parameters of interest. Likewise at the among species level, it is
indispensable for examining patterns of diversification over time. First, you
need to be familiar with some tree terminology.
How can evolutionary insights
help control pathogens?
Antiretroviral therapy
•
Currently, combination
therapy involves some
combination of reverse
transcriptase inhibitors and
protease inhibitors
How does drug resistance evolve?
How should it be avoided?
Why do we get sick?
or
Why are humans not perfect
(present company excepted)?
•
•
Also pain, nausea, vomiting, diarrhea, anxiety, fatigue, sneezing,
inflammation, anaemia, morning sickness
Do we do a disservice by blocking these defenses?
Case study: fever and neurosyphilis
•
Julius Wagner-Jauregg noted that some
syphilis patients improved after getting
malaria and that syphilis was rare in areas
where malaria was common
•
intentionally infected thousands of syphilis
patients with malaria
•
remission rates for syphilis increased from
less than 1 percent to 30 percent
•
Won the 1927 Nobel Prize for medicine or
physiology, but isn’t talked about much these
days…
Where did HIV/AIDS come
from? When? How?
Will avian flu jump into
humans?
Why do we have to keep
developing new vaccines
against flu?
(5) Predicting the future of influenza
Next class:
Evolutionary fundamentals….
1. Stearns handout
2. Darwin reading:
http://www.literature.org/authors/darwin-charles/the-originof-species/