1. Why evolution: genetic variation is the theme

2. Outline • Review of DNA • Molecular genetics has changed how we think about evolution • We need to understand evolution to understand how virulence arises

3. mlw Part 1: why DNA and evolution? • The fundamental requirement for evolution is heritable variation

4. DNA is the genetic material • DNA has four bases • Each group of three bases codes for one amino acid and is called a codon • There are 43 codons and 20 amino acids; therefore the code is redundant

5. The genetic code

6. mlw Part 2: genetics and evolution • Evolutionary thought was revitalized by molecular genetics

7. Mutations • Source of all genetic variation • Therefore the source of evolutionary novelty • Happen at random • Mostly from errors in DNA replication • Sometimes from environmental sources

8. Mutations • Link between macro and microevolution

9. What is a species? • A species is a group of actually or potentially interbreeding populations which are reproductively isolated from other such groups. (Mayr, 1942)

10. Speciation • Process by which two species become distinct • Allopatric: random mutation(s) causes sterility • Sympatric: random mutations which prevent mating are selected

11. mlw Part 3: why everyone needs molecular evolution • Examples: • Understanding DNA fingerprinting requires knowledge of evolution • A newly discovered evolutionary mechanism suggests new paradigms for evolution and caution in agritech • Antibiotic resistance • Drug discovery

12. Uses of DNA fingerprinting • Paternity analysis • Identification • Forensics

13. DNA fingerprinting http://www.biology.washington.edu/fingerprint/dnaintro.html

14. B C D E A Ancestral pop. Population history

15. B C D E A Population history

17. Biotechnology and evolution • Virulence and antibiotic resistance

18. 1950: P-element D. melanogaster D. willistoni 30 - 40 my Ancestral Drosophila Horizontal transfer

19. Horizontal transfer • Different from parent/offspring inheritance (vertical transfer): no hybridization necessary • Science of genomics increased our ability to detect these events • Newly perceived force in disease evolution

20. Horizontal transfer • Genes that cause virulence in tuberculosis were horizontally acquired from another bacteria • Horizontal transfer accounts for transfer of “pathogenicity islands” among Staphylococcus aureus

21. Darwin’s idea of the tree of life

22. Revised view of “shrub” of life

23. Antibiotic etc. resistance • 50% of tuberculosis cases in NYC are antibiotic resistant. Cause: artificial selection due to overuse of antibiotics • Takes about 10 years to design a new antibiotic and bring it to market! • Resistance to antivirals: very little H1N1 resistance in the US so far… limited use of tamiflu helping? mlw

24. Conclusions • Genetics informs evolution • Evolution informs genetics mlw

25. HIV, phylogeny, and crime Theory: man in Louisiana deliberately infects ex-lover with HIV, hepatitis C. How to demonstrate this in a court of law? Enter David Hillis, U. Texas Austin, professor turned crimefighter

27. Null hypothesis: other source of infection Prediction: victim’s HIV isolates will be no more closely related to the alleged source’s, than random HIV isolates from the local population Test: construct phylogeny of HIV from local population, including the victim and alleged source of infection

28. Possible phylogenies victim victim alleged source alleged source Null hypothesis Alternative hypothesis