Assigned readings

1. Assigned readings • Chapter 1 of Zimmer and Emlen text--The virus and the whale: how scientists study evolution.

2. Biological evolution • Any change in the inherited traits (genetic structure) of a population that occurs from one generation to the next. • Note that evolution is a populationprocess that occurs from generation to generation. • The above definition is a definition of Microevolution.

3. Biological evolution • The microevolutionary changes in genetic structure of a population over time can lead to substantial changes in the morphology of organisms over time and the origin of new species. • Such changes are referred to as Macroevolution.

4. Why study evolution? • Evolution explains the diversity of life. All living things are related to each other and are the products of millions of years of evolution. • Understanding evolution allows us to understand why the living world is the way it is. We can understand e.g., the similarities and differences between species, as well as their adaptations and their distributions.

5. Why study evolution? • There are also practical reasons to study evolution. • Evolution allows us to understand the evolution of disease organisms such as viruses and bacteria and combat them.

6. Why study evolution? • Evolution also gives us insight into such “big” questions as: • “How did we get here?” and • “How did thought and language evolve?”

7. Evolution case studies • Whales: mammals gone to sea • Viruses: the deadly escape artists

8. How do we know whales are mammals? • Whales share synapomorphies(shared derived characters) with mammals • Mammary glands • Three middle ear bones • Single jaw bone (dentary) • Hair (in developing embryos) • Similarities with fish [streamlining, fins] arose through convergent evolution

9. Whale evolution • Whales are aquatic mammals that evolved from terrestrial ancestors through the process of natural selection by which individuals that possessed traits that best fitted them to life in water left behind the most offspring.

10. Fossil whales • The evolution of whales is well documented by fossil discoveries. • Modern whales have peg-like teeth or baleen for feeding. Early fossil whales such as Dorudon (40 mya) however had more complex teeth that were similar to those of contemporary terrestrial mammals.

11. Dorudon

12. Dorudon and modern whales share numerous features of the skull in common, including a distinctively thick-walled ectotympanic bone. • The same distinctive bone is found in Pakicetusa terrestrial wolf-like animal from 50 mya.

14. Pakicetus • Pakicetus also possesses a distinctive ankle bone called the astragalus. In Pakicetus it has a double-pulley like morphology and this structure is found only in artiodactyls (hoofed mammals such as cows, pigs and deer).

15. Fossils reveal links to land mammals • Shape of astragalus connects to artiodactyls

16. These and other fossil discoveries have enabled biologists to construct a phylogentic tree (a tree of branching relationships) that depicts the evolutionary history of the group.

18. Evolution case studies • Whales: mammals gone to sea • Viruses: the deadly escape artists

19. Viruses • Your text has a nice discussion of the evolution of the flu virus. You need to read it and be familiar with it. • We will discuss a different example in class– the HIV virus to illustrate the process of natural selection.

21. Natural History of HIV/AIDS • Acquired Immune Deficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV).

22. Scale of problem • WHO estimate in 2012 -- 35.3 million people living with HIV/AIDS • In 2012 1.3 million people died of AIDS

23. The Human Immunodeficiency Virus • HIV is an intracellular parasite • Parasitizes macrophages and T-cells of immune system • Uses cells enzymatic machinery to copy itself. Kills host cell in process.

24. How HIV enters the cell • HIV binds to two protein receptors on cell’s surface : CD4 and a coreceptor, usually CCR5. • Host cell membrane and viral coat fuse and virus contents enter cell.

26. What the virus inserts • RNA genome and three enzymes: • Reverse transcriptase • Integrase • Protease

28. Viral DNA inserted in host DNA produces HIV mRNA and all components of virus. • Viral particles self assemble and bud from host cell.

29. HIV budding from human immune cell

30. HIV hard to treat • Because HIV hijacks the host’s own enzymatic machinery: ribosomes, transfer RNAs, polymerases, etc. it is hard to treat. • Why would that be?

31. How HIV causes AIDS • Immune system destroys virus particles in bloodstream and cells infected with virus. • Unfortunately, HIV infects cells critical to immune system function.

32. How HIV causes AIDS • HIV invades immune system cells called helper T cells. • When a helper T cell is activated (by encountering an antigen [something foreign], it divides into memory T cells and effector T cells.

33. Memory T cells • Memory T cells are : • long-lived • generate an immune response quickly if the same foreign protein is encountered again.

34. Effector T cells • Effector T cells attack HIV by: 1. Producing chemokinesthat stimulate B cells to produce antibodies to the virus. 2. Stimulating macrophages to ingest cells infected with the virus. 3. Stimulating killer T cells to destroy infected cells displaying viral proteins.

35. Why is HIV hard to treat?Viral disguise • First round of infection with HIV reduces the pool of CD4 Helper T cells . • Loss of CD4 helper T cells cells is bad, but immune system now ready to recognize HIV. • What’s the problem?

36. Why is HIV hard to treat?Viral disguise • Virus mutates and the proteins on its outer surface (gp120 and gp41) change. • The new surface proteins are not recognized by the immune systems memory cells. • Mutants evade immune system and begin new round of infection

37. Why is HIV hard to treat?Viral disguise • Each cycle of mutation and infection reduces the numbers of helper T cells because they are infected by virus and destroyed. • Over time the body’s supply of helper T cells becomes exhausted and the immune system collapses.

38. Why is HIV hard to treat?Drug resistance. • AZT (azidothymidine) -- first HIV wonder drug • AZT interferes with HIV’s reverse transcriptase, [the enzyme the virus uses to convert its RNA into DNA so it can be inserted in the host’s geneome].

39. Why is HIV hard to treat?Drug resistance. • AZT is similar to thymidine (one of 4 bases of DNA nucleotides) but it has an azide group (N3) in place of hydroxyl group (OH). • An AZT molecule added to DNA strand prevents the strand from growing.

41. Why is HIV hard to treat?Drug resistance. • AZT successful in tests but patients quickly stopped responding to treatment. • Evolution of AZT-resistant HIV in patients usually took only about 6 months.

43. How does resistant virus differ? • The reverse transcriptase gene in resistant strains of HIV differs from non-resistant strains. • Mutations are located in active site of reverse transcriptase. • These changes prevent AZT binding to DNA chain but allow other nucleotides to bind.

45. How did resistance develop? • HIV reverse transcriptase very error prone. • About half of all DNA transcripts produced contain an error (mutation). • There is thus VARIATION in the HIV population in a patient.

46. HIV’s high mutation rate makes the occurrence just by chance of AZT-resistant mutations almost certain. • NATURAL SELECTION now starts to act in the presence of AZT

48. Selection in action • The presence of AZT suppresses replication of non-resistant strains. • Resistant strains are BETTER ADAPTED to the environment. • There is thus DIFFERENTIAL REPRODUCTIVE SUCCESS of HIV strains. Resistant strains produce more offspring than non-resistant.

49. Selection in action • Resistant strains replicate and pass on their resistant genes to the next generation. • Thus resistance is HERITABLE.

50. Selection in action • AZT-resistant strains replace non-resistant strains. The HIV gene pool changes from one generation to the next. • EVOLUTION has occurred.