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

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Any 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.

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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.

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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.

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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.

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Evolution also gives us insight into such big questions as: How did we get here? and How did thought and language evolve?

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Whales: mammals gone to sea Viruses: the deadly escape artists

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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

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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.

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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.

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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 Pakicetus a terrestrial wolf-like animal from 50 mya.

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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).

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Shape of astragalus connects to artiodactyls

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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.

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Whales: mammals gone to sea Viruses: the deadly escape artists

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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.

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Acquired Immune Deficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV).

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WHO estimate in 2012 -- 35.3 million people living with HIV/AIDS In 2012 1.3 million people died of AIDS

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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.

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HIV binds to two protein receptors on cells surface : CD4 and a coreceptor, usually CCR5. Host cell membrane and viral coat fuse and virus contents enter cell.

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RNA genome and three enzymes: Reverse transcriptase Integrase Protease

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

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HIV budding from human immune cell

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

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

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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.

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

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Effector T cells attack HIV by: 1. Producing chemokines that 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.

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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. Whats the problem?

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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

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Each cycle of mutation and infection reduces the numbers of helper T cells because they are infected by virus and destroyed. Over time the bodys supply of helper T cells becomes exhausted and the immune system collapses.

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AZT (azidothymidine) -- first HIV wonder drug AZT interferes with HIVs reverse transcriptase, [the enzyme the virus uses to convert its RNA into DNA so it can be inserted in the hosts geneome].

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AZT is similar to thymidine (one of 4 bases of DNA nucleotides) but it has an azide group (N 3 ) in place of hydroxyl group (OH). An AZT molecule added to DNA strand prevents the strand from growing.

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AZT successful in tests but patients quickly stopped responding to treatment. Evolution of AZT-resistant HIV in patients usually took only about 6 months.

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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.

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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.

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HIVs 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

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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.

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Resistant strains replicate and pass on their resistant genes to the next generation. Thus resistance is HERITABLE.

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

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Evolution of HIV population in an individual patient

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There is variation in population some members of population better adapted than others That 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.

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Many different 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 hosts genome.

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We know treatment with a single drug will not be successful for long. Why?

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Multi-drug cocktails (referred to as HAART [Highly Active Anti-Retroviral Treatments] have proven successful. HAART cocktails combine different drugs (e.g. two reverse transcriptase inhibitors and a protease inhibitor). Why do HAART cocktails work?

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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.

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Multi-drug treatments have proven very successful in reducing viral load and reducing mortality of patients.

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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.

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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.

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A downside of HAART therapy is that many patients experience severe side effects. Because of severe side effects 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?

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Where did HIV come from? HIV similar to a virus in monkeys and apes called SIV (simian immunodeficiency virus). To identify ancestry of HIV scientists have sequenced various HIV strains and compared them to various SIV strains.

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HIV-1 is most similar to an SIV found in chimps http://animals.nationalgeographic.co m/animals/mammals/chimpanzee/

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HIV-2 is most similar to an SIV found in a monkey called the sooty mangabey. http://pin.primate.wisc.edu/factsheets/ entry/sooty_mangabey/cons

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HIV-1 occurs in three different subgroups (called M,N and O) and each appears closely related to a different chimpanzee SIV strain.

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Thus 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.

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Sequence data from several group M strains has been used to estimate when HIV moved from chimps to humans. Korber et al. (2000) analyzed nucleotide sequence data for 159 samples of HIV-1 strain M. Extrapolating from rates of change of different strains suggests that subgroup M probably infected humans in the early 1930s.

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To summarize: our understanding of evolutionary biology has enabled us to: 1. understand why HIV is so hard to treat 2. devise treatment methods that take evolution into account and 3. reconstruct the likely history of the disease.

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The process of Evolution is widely misunderstood and many misperceptions are common.

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All scientific theories are backed by multiple lines of evidence A theory is not just a hunch. A theory is a broad, overarching explanation for a major aspect of the natural world that has been extensively tested over time. Other scientific theories?

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Other scientific theories Gravity Plate tectonics Germ theory Atomic theory of matter

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The second law holds that disorder increases in closed systems ( entropy always increases). Some creationists argue that because evolution often results in the development of more complex forms from less complex that the first law is violated. Whats the flaw in the argument?

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The Earth is not a closed system. The sun provides a constant input of energy.

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Natural selection is a crucially important mechanism of evolutionary change but it is not the only one Other mechanisms include: Genetic drift Sexual selection

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Evolution includes random and non-random components Mutations occur randomly But, natural selection is completely non-random. Selection favors mutations that increase the survival and reproduction of the organisms that possess them. Selection allows beneficial changes to accumulate from generation to generation.

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Convergent evolution also demonstrates that evolution is non-random Similar body forms evolve when environments are similar. (E.g. fish, whales, seals and sharks all have streamlined bodies that easily move through water).

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Evolution cannot anticipate the needs of an organism Mutations do not occur because they would be useful. If beneficial mutations happen to occur by chance they may increase in frequency through selection

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Evolution is not ladder-like New species result from branching events Evolutionary patterns are bush-like not ladder- like.

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Evolution can also move from complex to simple e.g. mitochondria evolved from free-living bacteria Parasitic tapeworms have no digestive system.

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Evolution only works on inherited traits Acquired changes are not passed to offspring. No matter how much you practice a musical instrument you cannot pass that ability on to your child.

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Populations evolve; individuals do not Evolution 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)

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Natural selection favors traits that increase reproductive success Cooperative traits are beneficial under many conditions. Cruelty is a human concept Nature is not cruel. Rather Nature is pitilessly indifferent.

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Higher and lower are just human judgment calls. All organisms are well adapted to the environment

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Remember: All living organisms are the product of millions of years of selection and its hard to improve them. Thats why most mutations are harmful.

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Constraints and trade-offs limit how well organisms can adapt.

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Evolution selects traits that are beneficial for individuals or their genes Traits that are bad for individuals (or genes) will not be selected for even if they are good for the species as a whole.