01.Intro_evidence1.pdf
- 1. Lecture 1 HIV as a case study for contemporary evolution
- 2. Approach Each week: core set of topics + Examples of its application and evidence
- 3. Evolution What is it and why should you care? Evolution is key to understanding many biological processes: - Historical: How do species arise? - Contemporary: Consequence of biodiversity loss - Ecological processes: Host-parasite interactions - Human health: Evolution of drug resistance, cross- species disease transmission - And much more.
- 4. Lecture 1 The case for evolutionary thinking: HIV (and a little DNA review)
- 5. Outline today 1. DNA - what and where 2. HIV exemplifies many aspects of evolution
- 6. Evolution and DNA • Not all evolutionary studies use DNA • Phenotype is also important • Phenotype = Observed traits in an individual
- 7. Evolution and DNA • Not all evolutionary studies use DNA • Phenotype is also important • Phenotype = Observed traits • But we need to understand how DNA contributes • Genotype = the genes the individual has
- 8. Review: Remember DNA? Important to understand: • What is DNA? • Where is DNA? • How is DNA replicated? • How do we get new combinations?
- 9. Review: DNA You probably know a cartoon version of DNA You know it’s in the nucleus
- 10. Review: DNA • A complex molecule. Mostly made of: • Carbon, Hydrogen, Oxygen, Nitrogen, and Phosphorus (CHONP) Credit: Zephyris
- 11. A C T G • Purines - Double ring. A and G • Pyrimidines- Single ring. C and T (and U) This will be important later when we talk about types of mutations.
- 12. Only one way to pair them: Sug ar Sug ar Sug ar A denine( A ) T h ymine( T ) G uanine( G ) C yt os ine( C ) Sug ar / 2 0 1 7 Pea r s onEdu c a t ion , In c . Two hydrogen bonds Three hydrogen bonds
- 13. Review: DNA • Often simplified by just reading one strand: A C T A G A C T A G A C T A G A C T A G A C C A T A C C A G A C T A G A C T A G T G A T C 5 ′ 3 ′ 3 ′ 5 ′ / 2 0 1 7 Pea r s onEdu c a t ion , In c .
- 14. Molecular sequence data Here, each row is the DNA sequence found in one individual individual 1 individual 2 individual 3 individual 4 individual 5 individual 6 individual 7 A C T A G A C T A G A C T A G A C T A G A C C A T A C C A G A C T A G Mutations
- 15. Where is DNA? It’s in the nucleus! Animal cell Nucleus with nuclear DNA Plant cell
- 16. Some organelles have DNA too • Mitochondria - in both plants and animal cells SEM image (the dots are ribosomes)
- 17. Some organelles have DNA too • Chloroplast - photosynthetic material in plant cells
- 18. Organelles with DNA? These originate from ancient endosymbiosis of free living bacteria Eng ul f ingofox yg en- us ingnonph ot os ynt h et ic prokaryot e, wh ic h bec omesamit oc h ondrion A nc es t orofeukaryot icc el l s( h os tc el l ) M it oc h ondrion C h l oropl as t A tl eas t onec el l Eng ul f ingof ph ot os ynt h et ic prokaryot e M it oc h ondrion N onph ot os ynt h et ic eukaryot e Ph ot os ynt h et iceukaryot e
- 19. Why is this important? • Mitochondria and chloroplasts both have many copies in each cell cytoplasm • Only maternally inherited • Different replication machinery, so different mutation rates (more on this in lecture 4)
- 20. What’s the difference? • What is the impact of different copy number, inheritance, and mutation rate? • Example from birds in Australia. • Different patterns in nuclear and mitochondrial genes. • There can be a mismatch in the information in these genes! Morales et al (2017) Molecular Ecology 26(12):3241 mitochondrial nuclear This is a citation. The originial publication that made this picture Eastern Yellow Robin
- 21. What’s the difference? When we study evolution, we must remember what we are measuring. We might get different evidence from: - a mitochondrial gene - a nuclear gene - counting the number of hairs on a leg
- 22. What’s the difference? When we study evolution, we must remember what we are measuring. We might get different evidence from: - a mitochondrial gene - a nuclear gene - counting the number of hairs on a leg - bird songs
- 23. What’s the difference? When we study evolution, we must remember what we are measuring. We might get different evidence from: - a mitochondrial gene - a nuclear gene - counting the number of hairs on a leg - bird songs Genotypes
- 24. What’s the difference? When we study evolution, we must remember what we are measuring. We might get different evidence from: - a mitochondrial gene - a nuclear gene - counting the number of hairs on a leg - bird songs Phenotypes
- 25. Summary of DNA • Complex molecule with two strands • Composition can be summarized ACTG • Different traits (i.e. genotypes and phenotypes) ---> with different evolutionary histories Questions??
- 26. Outline today 1. DNA - what and where 2. HIV exemplifies many aspects of evolution
- 27. How HIV uses cells to replicate
- 28. 1. Mutation and selection • Early HIV treatment: AZT • Drug mimic “T” during replication • Stops reverse transcription
- 29. AZT mimics Thymine (ATGC) and stops reverse transcription
- 30. AZT stops working after a few years. • Why? • Have a closer look at the RT (reverse transcriptase) active site • Resistant viruses had a small change at this site • This RT worked in the presence of AZT Here: mutation causing resistance (Chapter 5)
- 31. Did AZT cause mutations? • No! • The drug (AZT) selected for resistant mutants that were already there and arose randomly Here: mutation causing resistance (Chapter 5)
- 32. Did AZT cause mutations? Before After • Before drug treatment, no advantage to being resistant • This is a fundamental idea in evolutionary biology
- 33. Did AZT cause mutations? Before After treatment Evolution within a single patient
- 34. Did AZT cause mutations? Before After Selection for resistant types Future infections more likely to be resistant
- 35. HIV is always evolving in patients • Random mutations accumulate • This shows two different genes from HIV, collected from one person • Most mutations have little-to-no effect Zanini et al (2015) eLife 2015;4:e11282
- 36. Court case in Louisiana • Relationships among HIV strains used to show source of HIV infection • A doctor injected his girlfriend with a syringe containing HIV • She developed HIV • He argued in court that she could have contracted it elsewhere
- 37. Court case in Louisiana • Relationship among HIV strains in community (1 gene) • The victims virus is nested within the sequences from the doctor’s patients • This evidence led to a conviction (Metzker et al (2002) PNAS: 99(22)14292)
- 38. • We can construct phylogenies that go back farther in time • Show multiple origins of HIV from wild primates • But only 1 group responsible for most of the epidemic (group M) • More on phylogenetics in chapter 4 Higher level relationships
- 39. Summary • Review: • DNA structure • Where do we find DNA • Evidence for evolution: genotype and phenotype • HIV virus exemplifies many aspects of evolution • Early drugs selected for existing resistant genotypes • Phylogenetics help resolve relationships: • Between strains in people • Among species, showing historical movements
- 40. Questions? • Review: • DNA structure • Where do we find DNA • Evidence for evolution: genotype and phenotype • HIV virus exemplifies many aspects of evolution • Early drugs selected for existing resistant genotypes • Phylogenetics help resolve relationships: • Between strains in people • Among species, showing historical movements