Emerging Diseases. Biosciences in the 21 st Century Dr. Amber Rice October 26, 2012
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1 Emerging Diseases Biosciences in the 21 st Century Dr. Amber Rice October 26, 2012
2 Outline Disease emergence: a case study Introduction to phylogenetic trees Introduction to natural selection How do pathogens shift hosts? The evolution of virulence
3 Disease emergence: a case study SARS: Severe Acute Respiratory Syndrome First detected in China, November 2002 Spread quickly 10% fatality rate Nature, 2003
4 Disease emergence: a case study What was it? Where did SARS come from?
5 Outline Disease emergence: a case study Introduction to phylogenetic trees Introduction to natural selection How do pathogens shift hosts? The evolution of virulence
6 Phylogenetic tree: A visual representation of the evolutionary history of populations, genes, or species
7 Constructing phylogenies with sequence data
8 Reading a phylogenetic tree
9 No currently existing species is ancestral to any other
10 Different arrangements show the same relationships There is no linear ancestor-descendent relationship! Humans did not evolve from cats or fish!
11 Phylogeny of HIV Three separate introductions from chimpanzees
12 Back to our case study: the emergence of SARS Palm civet Bat
13 Outline Disease emergence: a case study Introduction to phylogenetic trees Introduction to natural selection How do pathogens shift hosts? The evolution of virulence
14 What is evolution? Evolution is a change in a population s allele frequencies over time. Generation t Generation t+1 AA AA Aa aa Aa AA aa AA AA AA time Aa AA Aa aa AA aa Aa AA Aa AA 70% A 30% a 60% A 40% a
15 Natural selection is one mechanism of evolution Natural selection: differential reproductive success Non-random Not forward-looking, can only work with existing variation Only adaptive mechanism of evolution Figure: Univ. of Calif. Mus. of Paleontology s Understanding Evolution Site
16 Evolution by natural selection Ingredients needed for evolution by natural selection Variation in traits Inheritance Differential reproduction (natural selection) End result: Traits that increase reproductive success increase in frequency in a population. Figure: Univ. of Calif. Mus. of Paleontology s Understanding Evolution Site
17 Outline Disease emergence: a case study Introduction to phylogenetic trees Introduction to natural selection How do pathogens shift hosts? The evolution of virulence
18 Shifting to another host species phi 6: virus that infects bacteria (bacteriophage) phi 6 only infects Pseudomonas syringae
19 Shifting to another host species Could phi 6 switch hosts? Plated on 14 different Pseudomonas species A few viruses infected and survived All had mutation in protein for attaching to host Duffy et al. 2007
20 Shifting to another host species Once in a new host, must adapt quickly Slow growth can lead to extinction Host switching leads to strong selection: Infection Evade immune system and replicate What factors allow pathogens to evolve quickly?
21 Outline Disease emergence: a case study Introduction to phylogenetic trees Introduction to natural selection How do pathogens shift hosts? The evolution of virulence
22 Evolution of virulence: a trade-off
23 Mode of transmission affects virulence Direct transmission, vectorborne, waterborne
24 Mode of transmission affects virulence
25 Mode of transmission affects virulence
26 Back to our case study: virulence in SARS Wanted: an animal model for SARS Problem: SARS slowly replicates in mice, but mice do not get sick Solution: create selection for increased virulence of SARS in mice 1. Infect mouse with SARS 2. After 2 days, purify virus from lungs and infect new mice 3. Repeat, 14 times Roberts A, Deming D, Paddock CD, Cheng A, et al. (2007)
27 Back to our case study: virulence in SARS Infected with SARS Infected with MA15-low dose Infected with MA15-high dose Roberts A, Deming D, Paddock CD, Cheng A, et al. (2007)
28 Evolution of virulence: implications for public health Select for lower virulence by interfering with transmission Improve hygiene Wear masks Provide clean water Widespread vaccination
29 Current research aims Can we predict which pathogens are more likely to shift to humans? What makes some strains so much more deadly than others? How can we develop effective new vaccines and drugs?
30 Key points New diseases are constantly arising Evolution can help us determine 1. what they are 2. where they came from 3. how they infected humans 4. how they become more/less virulent 5. how best to fight them No currently existing species is ancestral to any other Virulence is a trade-off between fast replication and transmission Transmission mode affects virulence
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