Presentation on theme: "Assigned readings Chapter 1 of Zimmer and Emlen text--The virus and the whale: how scientists study evolution."— Presentation transcript:
1 Assigned readingsChapter 1 of Zimmer and Emlen text--The virus and the whale: how scientists study evolution.
2 Biological evolutionAny change in the inherited traits (genetic structure) of a population that occurs from one generation to the next.Note that evolution is a population process that occurs from generation to generation.The above definition is a definition of Microevolution.
3 Biological evolutionThe 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 VirusesYour 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.
9 Natural History of HIV/AIDS Acquired immune deficiency syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV).Disease first described in 1981.Transmitted through transfer of bodily fluids.Immune system attacked. Victim dies of secondary infections.
10 Scale of problem More than 60 million people so far infected. Mortality so far about 20 million.Projected mortality by million livesResponsible for about 5% of all deaths worldwide.Approx. 8,000 deaths per day.
11 The Human Immunodeficiency Virus HIV, like all viruses, is an intracellular parasiteParasitizes macrophages and T-cells of immune systemUses cells enzymatic machinery to copy itself. Kills host cell in process.
12 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.
18 HIV hard to treatBecause HIV hijacks the host’s own enzymatic machinery: ribosomes, transfer RNAs, polymerases, etc. it is hard to treat.Drugs that targeted these would target every cell in the hosts body
19 Progress of an HIV infection Three stagesAcuteChronicAIDS
20 Acute Viral load increases rapidly CD4 helper T cell level declines Immune system mobilizesViral load declines, CD4 T cell level increases
21 Chronic HIV not eliminated Viral load increases slowly CD4 helper T cell levels slowly decline
22 AIDS CD4 helper T cell level drops so low immune system fails. Patient vulnerable to all infectionsLife expectancy of only 2-3 years
23 How HIV causes AIDSHuman body responds to infection with HIV by mobilizing the immune system.The immune system destroys virus particles floating in bloodstream and also destroys cells infected with virus.Unfortunately, the cells that HIV infects are critical to immune system function.
24 How HIV causes AIDSHIV invades immune system cells especially helper T cells.These helper T cells have a vital role in the immune system.When a helper T cell is activated (by having an antigen [a piece of foreign protein] presented to it, it begins to divide into memory T cells and effector T cells.
25 Memory T cellsMemory T cells do not engage in current fight against the virus.Instead they are long-lived and can generate an immune response quickly if the same foreign protein is encountered again.
26 Effector T cellsEffector T cells engage in attacking the virus. They produce signaling molecules called chemokines that stimulate B cells to produce antibodies to the virus.Effector T cells also stimulate macrophages to ingest cells infected with the virus.In addition effector T cells stimulate killer T cells to destroy infected cells displaying viral proteins.
27 Why is HIV hard to treat? Viral disguise First round of infection with HIV reduces the pool of CD4 Helper T cells (those that can recognize and attack HIV).Loss of CD4 cells costly, but immune system now primed to recognize viral protein.What’s the problem? Why isn’t HIV eliminated?
28 Why is HIV hard to treat? Viral disguise Virus mutates and the proteins on its outer surface (gp120 and gp41) change.These surface proteins are not recognized by the immune systems’ memory cells.Mutants survive immune system onslaught and begin new round of infection
29 Why is HIV hard to treat? Viral disguise Each round of infection reduces the numbers of helper T cells because they are infected by virus and destroyed.Furthermore, because each lineage of T cells has a limited capacity for replication after a finite number of rounds of replication the body’s supply of helper T cells becomes exhausted and the immune system eventually is overwhelmed and collapses.
30 Why is HIV hard to treat? Drug resistance. AZT (azidothymidine) was the first HIV wonder drugIt works by interfering with HIV’s reverse transcriptase, which is the enzyme the virus uses to convert its RNA into DNA so it can be inserted in the host’s geneome.
31 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. The azide blocks the attachment of next nucleotide in the DNA chain.If DNA cannot be completed, viral proteins cannot be made.
33 Why is HIV hard to treat? Drug resistance. AZT successful in tests although with serious side effects.But patients quickly stopped responding to treatment.Evolution of AZT-resistant HIV in patients usually took only about 6 months.
36 How does resistant virus differ? The reverse transcriptase gene in resistant strains differs genetically from non-resistant strains.Mutations are located in active site of reverse transcriptase.These changes selectively block the binding of AZT to DNA but allow other nucleotides to be added.
38 How did resistance develop? HIV reverse transcriptase very error prone.About half of all DNA transcripts produced contain an error (mutation).HIV has the highest mutation rate known for any biological entity.There is thus enormous VARIATION in the HIV population in a patient.
39 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
41 Selection in actionThe presence of AZT suppresses replication of non-resistant strains.Resistant strains are BETTER ADAPTED to the environment.Resistant strains reproduce more rapidly. There is thus DIFFERENTIAL REPRODUCTIVE SUCCESS of HIV strains. Resistant strains produce more offspring.
42 Selection in actionResistant strains replicate and pass on their resistant genes to the next generation.Thus resistance is HERITABLE.
43 Selection in actionAZT-resistant strains replace non-resistant strains. The HIV gene pool changes from one generation to the next.EVOLUTION has occurred: Remember evolution is change in the gene pool from one generation to the next.
44 Evolution of HIV population in an individual patient
45 Process of natural selection There is variation in population – some members of population better adapted than othersThat variation affects reproductive success – there is differential reproductive success as a result of natural selection.Because the variation is heritable – beneficial alleles passed to offspring and alleles become more common in next generation.
46 Using selection to devise better treatment regimens. Several different types of drugs have been developed to treat HIV.Reverse transcriptase inhibitors (e.g. AZT).Protease inhibitors (prevent HIV from producing final viral proteins from precursor proteins).Fusion inhibitors prevent HIV entering cells.Integrase inhibitors prevent HIV from inserting HIV DNA into host’s genome.
47 Using selection to devise better treatment regimens. Because HIV mutates so rapidly treatment with a single drug will not be successful for long.Is there a better way?
48 Using selection to devise better treatment regimens. Most successful approach has been to use multi-drug cocktails (referred to as HAART [Highly Active Anti-Retroviral Treatments]HAART cocktails usually use three different drugs in combination (e.g. two reverse transcriptase inhibitors and a protease inhibitor).
49 Using selection to devise better treatment regimens. Using multi-drug cocktails sets the evolutionary bar higher for HIV.To be resistant a virus particle must possess mutations against all three drugs. The chances of this occurring is a single virus particle are very low.
50 Using selection to devise better treatment regimens. If the same drugs were provided in sequence to an HIV population each time it faced a new drug it would need only a single mutation to gain resistance, which would then spread through the population.
51 Using selection to devise better treatment regimens. Offering drugs one at a time is analagous to providing a stairway that HIV must climb. Offering multiple drugs at once requires HIV to leap from the bottom to the top in a single bound, which is much more difficult
52 Using selection to devise better treatment regimens. Multi-drug treatments have proven very successful in reducing viral load and reducing mortality of patients.
55 Using selection to devise better treatment regimens. However, HIV infection is not cured. Reservoir of HIV hides in resting white blood cells. Patients who go off HAART therapy experience increased HIV loads.
56 Using selection to devise better treatment regimens. For patients on HAART whether HIV replication is stopped completely or not is crucial. In some HIV appears dormant and no replication means no evolution.In other patients replication occurs, although slowly. However, this allows HIV to mutate and resistance to develop. So far, few HAART regimens are effective for more than 3 years.
57 Using selection to devise better treatment regimens. Other downside of HAART therapy is that many patients experience severe side effects.These patients have difficulties maintaining their treatment regimen.
58 Using selection to devise better treatment regimens. Because of severe side effects of HAART therapy some doctors have advocated “drug holidays” for their patients (i.e. to have patients stop taking drugs for a while). From an evolutionary perspective does this seem like a good idea or not?
59 Because a drug holiday allows HIV to replicate it is likely to be a very bad idea. Every time HIV replicates it produces new mutants and this increases the chance that a resistant form of HIV will be produced.
60 Origins of HIV Where did HIV come from? HIV similar to viruses in monkeys called SIV (simian immunodeficiency virus).To identify ancestry of HIV scientists have sequenced various HIV strains and compared them to various SIV strains.
61 Origins of HIVHIV-1 is most similar to an SIV found in chimps and HIV-2 is most similar to an SIV found in a monkey called the sooty mangabey.
65 Origins of HIVThus appears that HIV-1 jumped to humans from chimps on at least 3 occasions.Most likely acquired through killing and butchering chimps and monkeys in the “bushmeat” trade.
66 When did HIV move to humans? Sequence data from several group M strains has been used estimate when HIV moved from chimps to humans.Korber et al. (2000) analyzed nucleotide sequence data for 159 samples of HIV-1 strain M. Constructed a phylogenetic tree showing relatedness to a common ancestor of the 159 samples.
71 Benefits of evolutionary understanding To summarize: our understanding of evolutionary biology has enabled us to understand why HIV is so hard to treat, devise treatment methods that take evolution into account and reconstruct the likely history of the disease.
72 Common misconceptions about Evolution The process of Evolution is widely misunderstood and most people have only a vague understanding of the principle mechanisms (natural selection, genetic drift) by which it occurs.As a result there are many misperceptions about how evolution occurs.
73 Evolution is “just” a theory All scientific theories are backed by multiple lines of evidenceA theory is not just a “hunch.” All theories provide broad, overarching explanations for major aspects of the natural world and have been extensively tested over time.Other scientific theoriesGravityPlate tectonicsGerm theoryEvolutionary theory is overwhelmingly accepted by scientists
74 Evolutionary biologists understand everything about the history of life Biologists continually discover new information about life and the biological world.All that new information fits or is understood within the context of an evolutionary framework , because evolutionary theory provides a unifying framework for all biology.
75 Evolution explains the origin of life Evolution deals with how life has changed after it originatedOther scientific fields address the origin of life, but an understanding of evolution especially the process of natural selection, is relevant to discussions of life’s origins.
76 Evolutionary biologists search for missing links Newspaper reports always seem to focus on “missing links.” In reality, the fossil record is very incomplete and finding a direct ancestor of a particular organism is unlikely.Available evidence strongly supports relationships between current and past species and fossil evidence sheds light on how traits evolved.
77 Evolution violates the second law of thermodynamics The second law holds that disorder increases in closed systems (entropy always increases).However, the Earth is not a closed system because the sun provides a constant input of energy.
78 Evolution is natural selection Natural selection is a crucially important mechanism of evolutionary change but it is not the only oneOther mechanisms include:Genetic driftSexual selection
79 Evolution is entirely random Evolution includes random and non-random componentsMutations occur randomlyHowever, natural selection is completely non-random and it results in the spread of mutations that increase the survival and reproduction of the organisms that possess them.Convergent evolution also demonstrates that evolution is non-randomPhenotypes are predictable when environments are similar
80 Organisms evolve adaptations they “need” Evolution cannot identify or anticipate the needs of an organismMutations do not occur because they would be adaptive in an environmentIf beneficial mutations happen to occur by chance they may increase in frequency through selection
81 Evolution is a march of progress Evolution is not ladder-likeNew species result from branching eventsEvolutionary patterns are bush-like not ladder-like.
82 Evolution always moves from simple to complex Evolution can also move from complex to simplee.g. mitochondria evolved from free-living bacteriaParasitic tapeworms do not possess a gut because they live attached to the intestines of their host and have no need to digest their own food. They just absorb predigested nutrients from their surroundings.
83 Evolution results from individuals adapting to environment Evolution only works on inherited traitsAcquired changes are not passed to offspring. No matter how much you practice a musical instrument you cannot pass that ability on to your child.Populations evolve; individuals do notEvolution results from changes in allele frequencies that result from the success or failure of individuals to reproduce (e.g. as a result of natural selection or sexual selection)
84 Organisms are perfectly adapted to their environment Natural selection can only work with available variationConstrained by physical limitations and developmentMany traits involved in trade-offse.g. human brain sizeStructures may have to perform multiple different tasks and cannot be equally good at all of them
85 Evolution happens for the good of the species Evolution selects traits that are beneficial for individuals or their genesTraits that are bad for individuals (or genes) will not be selected even if they are good for the species
86 Evolution promotes selfishness and cruelty Natural selection favors traits that increase reproductive successDifferent conditions select for different traitsCooperative traits are beneficial under many conditions.Cruelty is a human concept Nature is not cruel. Rather Nature is pitilessly indifferent.
87 Evolution seeks peaceful harmony in nature Natural selection favors traits that increase reproductive successCan result in overexploitation of resources, habitat destruction, the extinction of other species and many other non-harmonious outcomes.
88 Life can be divided into higher and lower forms All of life is adapted to the environment in numerous waysEnvironments differ so the adaptations to succeed in different environments differ also.One organism is not “superior” to another organism just because we think it’s simpler. For example, a jellyfish is beautifully adapted to the role of a floating sit-and-wait predator even though it has no brain.Remember all living organisms are the product of many millions of years of evolution and it’s hard to improve them. That’s why most mutations are harmful.
89 Evolution has produced a stable diversity of life Extinction means diversity is not stableMore than 99% of all species that have ever existed are extinct.There has and always will be constant turnover in the diversity of life.