Evolution and Modern Medicine: Understanding Pathogen Evolution and Human Health

1. Lecture 16: Chapter 14Evolution and Human Health

2. 1854 Cholera outbreak in London Traced back to centering around a water pump No one knew what caused it, but recognized the water was to blame somehow 1858-Louis Pasteur proposed that contagious diseases are caused by microorganisms This is Germ Theory, one of the most important for discoveries the development of modern medicine Evolution and Human Health

3. Sanitation, plus antibiotics responsible for drop of TB Tuberculosis death rates over time USA

4. Consider how much we’ve discussed AIDS, Malaria, Cystic Fibrosis, other genetic disorders Human medicine is tied to understanding Evolutionary Biology Phylogenetics can be very important for understanding human disease (can determine where a disease originates) Haitian cholera outbreak phylogeny

5. Can think about it as a conflict between populations of human cells vs. populations of pathogen cells Pathogen tries to convert host cells into more pathogen cells, host tries to stop this from happening Immune system is our defense mechanism Pathogens have high population sizes, short generation times, and high mutation rates! Understanding how the pathogen evolves helps us develop better medical responses to pathogens Medical consequences of pathogen evolution

6. From Flu Google news search 3/13/18 2017/2018 Flu killing up to 4000/week! Flu Virus Evolutionhttps://www.youtube.com/watch?v=8Ch48o4og8E

7. Flu Virus Evolution

8. Flu Virus Evolution

9. Flu Virus Evolution The hemagglutinin antigenic sites recognized by our immune system (in color)

11. (From the flu virus) Flu Virus Evolution

12. Flu Virus Evolution Why do some strains die out and others endure?

13. Stuff Flu Virus Evolution

15. Pandemic Flu Strains Hemagluttinin strains that have never been recognized by a human immune system can invade across the world…how can this happen?

16. Flu Virus Evolution If two strains infect a host at the same time, their genomes may recombine This means that they can swap some of their hemagluttinin genes Nucleoproteins are the viral protein most linked to specific hosts in flu Hence, humans can get swine or bird flu strains

17. Pandemic Flu Strains H3 strains not seen in humans until 1968 pandemic

18. Pandemic Flu Strains

19. Pandemic Flu Strains

20. Pandemic Flu Strains

21. Antibiotics are chemicals that kill bacteria by disrupting biochemical processes A major medical discovery that saves millions of lives For bacteria though, an antibiotic is an agent of selection (although not an antibiotic, consider the antiviral AZT and HIV)---this is what causes antibiotic resistence Multiple ways bacteria can become resistant---antibiotics are selecting for resistant bacteria Evolving Pathogens-antibiotic resistance

22. a) Frequency of Pneumonococcus resistance to penicillin in Icelandic children over timeb)seasonal pattern of antibiotic prescription and subsequent resistance

23. Costs (for the bacteria!) of antibiotic resistance in short vs long term There may be an initial cost, but it often does not persist! The resistant strains, if newly resistant, do not increase in frequency as quickly as the sensitive (non-resistant) strains If resistant strains are allowed to evolve over time, they do better than the sensitive strains! Resistant costs have been compensated for via evolution

26. 3 models to explain the evolution of virulence

27. 3 models to explain the evolution of virulence

28. 3 models to explain the evolution of virulence

29. Fast reproduction should be favored but also harms host more/more quickly Trade off between virulence and within-host reproductive rate of virus phage f1 that infects E. coli Vertical = from one host generation to the next when host cell divides Horizontal=from one host into another, when secreted virions invade a new host 8 day transmission f1 evolves to allow host cell to live longer/grow faster (less virulent) compared to the 1 day transmission

30. Stuff Medical consequences of pathogen evolution

31. Stuff Medical consequences of pathogen evolution

32. Can reconstruct phylogenetic and evolutionary history of cancer cells The mutations found in the tumor cells and the non-tumor cells allow us to better understand the progress of the cancerLiver cells divide out of controlCan see 4 lineages of tumor causing cells in this patientThe mutations in the tumor also appear in surrounding non-tumor cells---the mutations in surrounding cells allow for the tumor cells to form in some cases

33. Helps us understand human physiology and behavior relevant to medicine and public health Includes how modern culture may differ to environs humans were initially adapted to Selection thinking applied to humans

34. Selection thinking applied to humans Some Icelandic people carry a nonsynonmous substitution for the gene cystatin C Individuals who have allele L68Q die of stroke in early 30s 200 hundred years ago, they lived just as long….why? Salt/carbohydrate heavy diet Life span vs. year of birth for those with L68Q change in freq. of the allele

35. Selection thinking applied to humans Increase in myopia (nearsighteness)---studies show it is partially heritible We can correct our vision via glasses, contacts, lasers But why would it genes associated with it have made it this far in human evolution (why wasn’t it eliminated hundreds of thousands of years ago?) Possible that our modern lifestyle makes people who are only predisposed to myopia have it (reading, computers, tv, etc.) and it would not be “activated” in hunter-gatherer societies, even if the alleles were present Evidence from Inuit societies support this (adults who did not read much as kids have 5% rate of myopia, their kids in modern school systems have 42% myopia).

36. Fever Two possibilities

37. Does the bacteria cause the fever or does the iguana immune system cause the fever? Can test by reducing fever via aspirin Iguanas who did not develop fever all died!

38. What about in humans? Is fever adaptive to fighting pathogens? Really unclear! In some cases, suppressing fever may be best but not in other cases…