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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 • Understand the vertebrate immune system/defenses • 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. 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

  4. 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

  5. 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

  6. 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

  7. Phylogenetics interlude • In this case, we would infer a tree that correctly recapitulated the chain of infections…

  8. 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”

  9. 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?

  10. 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?

  11. Topics covered:

  12. 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

  13. evolution by natural selection • A process much like artificial selection, used by breeders of domesticated plants and animals to select for desirable traits,also happens in nature: • Individuals within populations are variable • The variations among individuals are, at least in part, passed on from parents to offspring. • In every generation, some individuals are more successful at surviving and reproducing than others • The survival and reproduction of individuals are not random: those with the most favorable variations are naturally selected

  14. Antiviral resistance: HIV and AZT

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

  16. 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?

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

  18. 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)

  19. The central role of parasites in evolution

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

  21. 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”

  22. 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.

  23. Figure 1-15

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

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

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

  27. 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

  28. What sorts of organisms make us sick?

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

  30. 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.

  31. Global impact of HIV/AIDS

  32. Are parasites always “bad”?

  33. 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

  34. ->Strict vertical transmission since ancient infection of ancestral host

  35. Why are some parasites so virulent compared with others?

  36. 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: • 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? • From the point of view of the pathogen. What are the differences between the agents that cause disease and those that do not?

  37. Inferrring lateral gene transfer (LGT) from sequence heterogeneity along the chromosome Neisseria meningitidis, 52% G+C (from Tettelin et al. 2000. Science)

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