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Goals of the course

ECOL/MCB/CPH/VSC 409/509 Evolution of Infectious Disease Dr. Michael Worobey BSW 324 worobey@email.arizona.edu 626-3456. Goals of the course. Learn some fundamental evolutionary theory as it relates to infectious disease

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Goals of the course

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  1. ECOL/MCB/CPH/VSC 409/509Evolution of Infectious DiseaseDr. Michael WorobeyBSW 324worobey@email.arizona.edu626-3456

  2. 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

  3. 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.

  4. Questions raised?

  5. SOME REASONS FOR STUDYING THE EVOLUTION OF INFECTIOUS DISEASE • We all have a vested interest since we’re susceptible and infectious disease touches everyone’s life • HIV, flu, colds, antibiotics, immune system

  6. SOME REASONS FOR STUDYING THE EVOLUTION OF INFECTIOUS DISEASE • 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

  7. SOME REASONS FOR STUDYING THE EVOLUTION OF INFECTIOUS DISEASE “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

  8. SOME REASONS FOR STUDYING THE EVOLUTION OF INFECTIOUS DISEASE 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

  9. SOME REASONS FOR STUDYING THE EVOLUTION OF INFECTIOUS DISEASE Infectious disease may help explain some “evolutionary scandals” such as the ubiquity of sex “Parasite Red Queen”

  10. SOME REASONS FOR STUDYING THE EVOLUTION OF INFECTIOUS DISEASE We’re all shaped to a great extent by our long arms race with infectious disease agents -examples?

  11. SOME REASONS FOR STUDYING THE EVOLUTION OF INFECTIOUS DISEASE 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?

  12. Topics covered:

  13. 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: • Adaptation • Conflicts • Trade-offs • Constraints

  14. What’s the role of parasites in the biological big picture?

  15. 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?

  16. In a population conforming to JMS’s assumptions, asexual females produce twice as many grandchildren as sexuals

  17. Case study I: Parasites and the advantage of sex Which reproductive mode is better: sexual or asexual? • Null model: (what a null model?) • A female’s reproductive mode does not affect the number of offspring she can make • A female’s reproductive mode does not affect the probability that her offspring will survive (John Maynard Smith, 1978)

  18. The central role of parasites in evolution

  19. How do humans and other animals protect themselves against pathogens?

  20. 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”

  21. 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.

  22. Figure 1-15

  23. How does the immune system work? How do diseases evolve in response to it? What are the consequences?

  24. Figure 3-23 MHC class I molecule presenting an epitope

  25. When and how did our immune defenses come to be?

  26. 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

  27. What sorts of organisms make us sick?

  28. The three domains of life BACTERIA ARCHEA * 0.1 CHANGES/SITE EUCARYA

  29. 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.

  30. Global impact of HIV/AIDS

  31. Are parasites always “bad”?

  32. 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

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