Sei sulla pagina 1di 2

08/31/2011 1. How can we study evolution? Evolution occurs slowly- difficult to observe directly.

. The evolution of lineage of organisms is the result of a singe sequence of events- we cant repeat the experiment. Horseshoe crab is a living fossil...looks identical to its ancestor. The genetics of the organism in relationship of the environment that it lives. Why do we study the science of evolution? Can we do anything useful with knowledge about how organisms evolve? 1. Chapter 1: a case study of evolution by natural selection 1. HIV- cause of acquired immune deficiency syndrome 2. To an evolutionary biologist: Hiv is a model organism that can increase our understanding of evolution. Can study hiv populations in great detail. 1. Because the virus mutates....variability....great model sstem because it tends to mutate. 2. To an aids researcher: understanding HIV evolution ca clarify its origins and contribute to strategies for treatent and intervention. 3. Evolves very rapidly-evolution over a period of weeks. 4. Easy to manipulate- we can watch populations evolve over and over. 5. Understanding Hiv evolution helps aids researchers to address: orgins of drug resistant hiv strains (natural selection) 6. strategies for treatment (natural selection, evolution of genes and proteins) 7. Hiv transmission among patients (population genetics, phylogenetics. 8. Non human sources of HIV (phylogenetics, ecological iteractions. 3. What is HIV? 1. Viruses are not alive, dont follow the cell theory. 2. They dont reproduce by themselves. Pretty good replication. 3. They need a host in order to survive. 4. Retrovirus: RNA genome. Reverse transriptase. Goes from RNA to DNA. We need to convert it form one genetic code to another. To co-op the system. Becase our cells have DNA, the RNA must be tured into RNA in order to make protein. 5. Mst organisms DNA->RNA->Protein 6. Retroviruses: Rna-dna-rna-protein (reverse transriptase is needed) 7. the hosts own immune response also contrbutes to the development of the immunodeficiency. (see fig. 1.5) 8. T-cells are like the generals. The ones that turn everything on. Killing t-cells cripples the immune system. Facing attack with the strongest players. If we dont have these cells, we can fight the infetion well. 4. Hiv life cycle: free virus ouside cells, fuses to host cells, release RNA, reverse transcriptrase into cell. (see handout) 5. How do we design an anti-hiv drug? What would you do or want to have happen? 1. Block reverse it doesnt allow for any more particles to be made. Preventing binding to t-cells. 2. Chemo,,,problematic because it kils both healthy and disease cells. 3. The perfect drug would prevent hiv from reporoducing, not affect human host cells. 4. Drugs that target specific stages inn te hiv life cycle. 5. AZT...RNa-dna 1. very promising early treatment

2. azidothymidin-mimics the nucleotide deoxythymidine, T. cant convert....process s stuck. 3. Normal nucleotides ave a hydroxyl group (oh, azt has an azide group (n3). It needs that OH group to continue the replication process. 4. Reverse transcriptase is tricked into building azt into the DNA copy. Adds to the 3' end. Dont have OH group....reaction wont go. Result: additional nucleotides cant be added. 5. Promising early results-but loss of effectiveness over time. Evlution of resistance to AZT. 6. Azt also causes serious side effects. Azt also fools dna polymerase in some cases so will disrupt dna synthesis. 7. The mutation probably occurred in the active site, so it doesnt bind the azt molecule. 8. Evolution of resistance to AZT: within months....we almost have resistance at a 100%. eventhough we are bombarding the system with AZT, we already have resistance...happened over and over again. 9. Which is changing? Human or virus? 1. Needs intracellular concentration of thymidine kinase. 2. The viral particle is response to the AZT in the environment was getting over the hum. 3. Hiv population has evolved from low resistance to high resistance. 4. How do the azt-resistant ones differ from the others? 5. The ones that are resistant to AZT had different active sites that could differentiate azt from the regular nucleotides. 6. Azt resistant variants of hiv have an advantage-ability to reproduce. 7. Where do the variants come from? 8. Mistakes-mutations are introduced at random throughout the genome when hiv copies RNA to DNA. 9. Result-genetically variable populatio. 10. Reverse transcriptase has a high error rate. No correction mehanisms. It replicates very fast. No corrector proteins. 11. What about a variant whose RT is better at recognizing legitimate nucleotides? 12. In the presence of azt, better at replicating itself. 13. It will increase in frequency. Azt is a selective agent among RT variants. 14. Population evlves as new variants with high reproductive fitness increase. 15. Natural selection can be observed in just a few months. 10. Natural selections for azt resistance will occu if four assumptions are true 1. viruses vary in their resistance to azt 2. resistance or lack of can be passed from one generation to the next. 3. Viruses ary in their ablity to reproduce. 4. Reproductive ability has to be linked to resistance. 11. HAART contains multiple medications to disrupt the replication process in different areas. 12. Prediction: resistance strains of virus out-reproduce non resistant strains inrease through time. 13. Is the evolution of restsinace unusual? Are there better drugs? 1.