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Department
Biology
Course
Biology 1001A
Professor
Tom Haffie
Semester
Fall

Description
Biology Midterm 1 Lecture 2 Before: TED talk 1. The general mechanisms by which vaccines protect against diseases.  Vaccines have the virus in them  They enter the body and create a defense  When the actual virus enters the body it will be able to identify the virus and attack  Therefore the time the virus enters the body and the attack time is not delayed by identifying the virus 2. Why developing a vaccine against HIV is relatively challenging, compared to other diseases.  It is challenging because HIV is always changing  It mutates rapidly so one vaccine could not work all the time 3. Why people are encouraged to get a flu vaccine each year (as opposed to one time only).  This is because the flu mutates slowly but over the course of a year there are different strands  So if you receive the vaccine each year you have a better chance of being immune to the new strand Evolution in action: HIV  the HIV pandemic began in 1981 when it was first discovered  It’s called a pandemic because it was found all around the world  South Africa was hit harder with HIV than anywhere else on the globe o Some reasons for this are because it is easier for diseases to be transmitted here o Standard of living is much less o Awareness is much less o More interactions with animals which causes infection  22.5 million sub-Saharan Africans living with HIV (2009) How?  HIV moved from chimpanzees (SIV) to humans (HIV) around 1908  This is called zoonosis o Which is a disease that can jump from animal to humans  Zoonosis occurred from humans eating chimp meat or being bitten by a chimp  Africa was “ground zero” for the virus Biology Midterm 1 After 32 years why is there no cure still?  HIV mutates very rapidly, more than anything we have seen before, including RNA viruses  Tremendous amount of genetic variation because of the mutation rate  This is why a vaccine can’t be created  Also challenging because it attacks the cells of the immune system  Disease was considered a “gay disease” so the research was slow  Low funding because it affects more countries that are in poverty Viruses don’t fit into the tree of life  Viruses are not living and don’t fit onto the tree of life  They border it  HIV is a retrovirus o RNA viruses which insert a DNA copy of their genome into the host cell in order to replicate  Antiviral drugs used to treat viruses have serious side effects o This is because viruses use the bodies building blocks of life such as cells and nucleotides o Viruses reside inside the host cell so when you destroy it you actually hurt part of the body The reason that retroviruses have such high mutations is because they do not follow the central dogma of molecular biology DNA Blue=normal purple=virus Replication Reverse transcription (no proof reading) Transcription RNA Translation protein - Reverse transcription is why more mutations occur  Which is the reverse of normal transcription, in which a sequence of nucleotides is copied from an RNA template during the synthesis of a molecule of DNA Biology Midterm 1 How HIV survives HIV hijacks immune cells  A viron (viral particle) enters the host cell by endocytosis  Reverse transcriptase catalyzes in two steps o First the synthesis of a DNA copy of the viral RNA then second the synthesis of a second DNA strand complementary to the first one  Integrase splices viral DNA into host DNA  Transcription and translation occur then new virions assemble and enter circulation  Then the immune system eventually collapses o Once the host cell is infected it may lyse and then the viron particles enter the blood stream causing more infection Since using antiviral drugs causes harm to the body biologists had to find a way to destroy the virus without causing the body harm  They did this by attacking unique steps of the virus such as reverse transcription AZT drug  AZT mimics thymidine and fools reverse transcription  In the mid 80’s it was considered a “wonder drug”  AZT takes the place of thymidine causing the synthesis of DNA to stop  AZT acts as an inhibitory drug because it stops DNA from being to add more nucleotides Why AZT didn’t cure?  When AZT first started to be used it stalled HIV turning into full blown AIDS  But eventually patients needed more and more of the drug because it stopped working as well  This is because the HIV virus began to evolve due to the selection pressure that was put on it by the use of AZT  Since HIV has such a high mutation rate, somewhere during these mutations it becomes resistant and is able to replicate in the presence of AZT Biology Midterm 1 Evolution of AZT resistance  Mutations created variation in AZT resistance  AZT-resistance passed from parents to offspring  Not all virions reproduce  When AZT is present some forms (AZT-resistant) are more likely to reproduce than others (AZT-susceptible)  Thus through natural selection the population changes Since it is inevitable for one drug to become resistant the thought was that if they used many drugs it would be less likely for the virus to become resistant  With many drugs inhibiting viral replication it becomes less probable that the virus will mutate at the same time in the exact way to become resistant to all the drugs  This is called a drug cocktail CCR5  CCR5 receptor is shown on the white blood cell where HIV normally binds  Sometimes the allele for CCR5 has mutated and is missing the part of the allele that codes for the region where HIV normally binds  Thus people who have the CCR5 32 allele are less likely to get HIV and have a higher resistance Evolutionary perspective of CCR5 32  The allele is not distributed evenly throughout the world…Why?  This can be explained because humans are also evolving which means mutations also occur just at a much slower rate  Even though Africa would typically be the most logical place for mutations to occur that are resistant to HIV, it is Europe that has the highest resistance o The reason for this could possibly be because the allele provided protection against some other disease in the past (Influenza pandemic) and has been favourite throughout the population now Biology Midterm 1 Summary: evolution in action 1. Evolution can be very fast 2. Even non-living things can evolve 3. HIV involves themes such as a. Mutations and variation b. Natural selection c. Evolutionary history d. Humans as an evolutionary force and as the products of evolution Biology Midterm 1 Lecture 3 Before: 7 characteristics that define all life 1. Display order  All life is arranged in highly ordered manners, with cell being the fundamental unit of life 2. Harness and utilize energy  Life required energy from environment and must use it to maintain ordered state 3. Reproduce 4. Respond to stimuli  Can make adjustments to structure, function and behaviour in response to external environments 5. Exhibit homeostasis  Regulate internal environment so that conditions remain the same 6. Growth and development  Increase cell count and change over time 7. Evolve  Populations change over course of generations to become better adapted Viruses are debatable between biotic and abiotic. One reason this is true is because they have some characteristics of life such as; reproducing and evolving over time. The characteristics of life are emergent because they emerge from many simpler interactions that in themselves do not have the properties of life.  Example. The property to harness energy is not a property of proteins or molecules but rather the ability emerges from interactions between them -Earth was formed approx. 4.6 billion years ago -Humans were formed around 150 000 years ago, very small compared to how long earth has been around -it took around 500 million years for the earth to cool to a temperature that could harbour life -Earth is in the habitable zone, this means that water can exist on our planet as a liquid which is fundamental to life. -so since we have many other solar systems in our galaxy it is possible that there are other habitable zones in the galaxy Biology Midterm 1 3 hypotheses as to where molecules were originally formed 1. Reducing atmosphere -The atmosphere had an absence of oxygen in primordial earth. People believed it was a reducing atmosphere because of the presence of large concentrations of hydrogen, methane and ammonia. These molecules have lots of hydrogen and reactions would occur with one another creating larger complex molecules. - Because there was no ozone layer in primordial earth, ultra violet rays were able to penetrate the earth, providing the energy needed to drive biologically important molecules to form - The miller-Urey experiment provided evidence that these molecules could be produced in a reducing environment. He found large quantities of urea, amino acids and lactic, formic and acetic acids. 2. Deep-Sea Vents - some believe the complex molecules could have originated on the ocean floor at the site of deep sea vent 3. Extra-terrestrial Origins - meteors often struck earth in primordial times. Thus these complex molecules could have come from out of our solar system -this theory is plausible because today scientists find many of these molecules on meteorites all the time -the only problem with these theories is that it does not explain how polymers were created. -there were no enzymes sophisticated enough to create these polymers - However there is one way that they could be synthesised; and that is in the layers of clay which are charged so that allows catalyzation of polymers. The Origin of Life Life cannot be define in one sentence rather is determined by a set of characteristics (above) Biology Midterm 1 Out of the 7 there are 3 that are the most important  Order  Reproduce  Evolve -using these 3 only to define life then some people may say that viruses are alive (Dennis) Eukaryotes Bacteria Archaea LUCA -Last Universal Common Ancestor  This means that everything that is alive on the planet today has descended from a single population of organisms that were exactly the same  The reason LUCA is believed is because it explains why the 3 domains of life are so biochemically similar. They all share o Cells made of lipids o Genetic system based on DNA o DNA-RNA- protein transfer of information o Common system of protein assembly (ribosomes) o ATP o Glucose and glycolysis  The picture above DOES NOT mean that LUCA was the first living thing ** What characteristics were the tree built on?  DNA and the gene sequencing that is similar throughout the 3 domains Why the term prokaryote is the wrong term  Bacteria and Archaea used to be lumped together into one group Biology Midterm 1 o This was wrong because it suggested that everything in the “prokaryote” group was evolutionarily related o This is not true o Bacteria and Archaea are no more related than bacteria and eukaryotes  Pro means “before” and karyote means “nucleus” o Thus suggests that LUCA did not have a nucleus which is wrong because new evidence indicates that LUCA had a nuclear envelope LUCA was somewhat eukaryotic  LUCA had a certain level of complexity that was lost due to reductive evolution or “streamlining” o Streamlining: make (an organization or system) more efficient and effective by employing faster or simpler working methods  The bacteria got rid of complexity because it was an advantage to them in the way that they could: o Replicate faster o Grow faster o Evolve faster Stromatolites  Require the metabolism of cyanobacteria  Found in Australia  Could have developed 3.5-4 billion years ago Pre Biotic Evolution: Before life occurred there were some evolutionary things happening, first let’s look at the requirements to form life: 1. Abiotic synthesis 2. Heritable information (reproduce) 3. Cells 4. Metabolism (photosynthesis and respiration) Now we can look at what happened before life existed and how it was created (Prebiotic evolution) 1. Geophysical stage  What was the composition of the earth and atmosphere?  WE KNOW ABOUT THIS 2. Chemical Stage  How could the building blocks of life be synthesized?  WE KNOW ABOUT THIS 3. Biological Stage Biology Midterm 1  How did the building blocks organize into living cells?  This is unclear  We are not sure how we went from Abiotic to biotic life Chemical Stage **at the chemical stage the Milner-Urey experiment proved that you do not need a living cell to make amino acids** it created other unanswered questions though, such as; 1. Development of polymers (didn’t produce proteins) 2. chirality Chirality  “handedness”  Example: you cannot superimpose your left and right hand  Therefore they are chiral  This happens in nature all the time  Another example: amino acids are chiral o D-alanine and L-alanine  They can have the same chemical and physical properties but are biologically very different! o In the 1950’s and 60’s an antiemetic drug was used to treat pregnant women with morning sickness o The problem was this it caused many birth defects o This was because the animatic drug was chiral to tetraogen o So even though only animatic was synthesized, once it was inserted into the cell it quickly became tetraogen which caused the birth defects Life is Homochiral  This means that “life” requires using ONE form of chiral NOT BOTH o We believe homochirality came about because there is so much specification on receptors that it had to choose only one chiral to be able to recognizes specific molecules  All life: L amino acids and D sugars (only uses one type) Biological Stage Heritable information, cells and metabolism **The biggest question biologically was how the central dogma evolved and developed**  This was unclear because transcription and translation both require an enzyme to catalyze Biology Midterm 1  But the only way to create enzymes was by translation and transcription  How did the first enzyme synthesize? RNA!!!! RNA -the molecule that can do it all -very important to origin of life** **tree built on RNA** Everything needed to know about RNA:  Relays information o mRNA  proteins o tRNA o rRNA  Structure o 3 dimensional o Not double stranded so it can fold in on itself o Can hydrogen bond  Function o RNA’s are catalytic o Ribozymes  Biological catalysts  Thomas Cech and Sidney Attmon won the Nobel prize in 198 for discovery catalytic properties of RNA  Not a protein but an RNA molecule  There play a role in precursor tRNA processing, intron excision and mRNA processing Ribosomes are ribozymes!  The part that transfers in a ribosome is a ribozyme  Peptidyl transferase activity Evolution of information transfer  Replication is never perfect  Which led to the development of proteins o Proteins can create enzymes, diversity (ribonucleoproteins)  DNA is more stable than RNA because of the replacement of Uracil the thymine o DNA is less likely to breakdown chemically Biology Midterm 1 Lecture 4 Before:  When reading tree diagrams know that; o Because two living things are closest on the diagram doesn’t mean they are the most closely related o The intersection where two living creatures meet is where an extinct creature evolved creating the two paths. Thus this is those two creates most closely related ancestor o Do no assume that because a line is long that no evolution has occurred. This generally indicates that the tree was not sampled accurately and has missing nodes Biodiversity The book describes evolutionary history in reverse  Start at present day and climb down the tree of life  8.7 million other species doing the same things (eukaryotes)  Branching points on the tree of life RENDEVOUS point  At each point we meet a new species and the groups MRNA (most recent common ancestor) Rendezvous 0. MRCA of all humans 1. Chimps and Bonobos -6 mya 2. Gorillas -7 mya 3. Orangutans -14 mya 4. Gibbons -18 5. Old World monkeys -25 6. New World monkeys -40 7. Tarsiers – 58 mya a. 5 species 8. Lemurs and Lorises – 63 mya a. 50 species b. MRCA of all PRIMATES 9. End-Cretaceous mass extinction- 65 mya 10. Rodents and Rabbits – 75 mya 11. Laurasiatheres- 85 mya a. Large group of placental mammals believed to have originated on the northern supercontinent of Laurasia. It includes shrews, hedgehogs, pangolins, bats, whales, most hoofed mammals, and carnivores, among others. 12. – 13. – Biology Midterm 1 14. Marsupials- 140 15. Monotremes- 180 16. Reptiles- 310 mya 17. Amphibians- 340 mya a. MRCA of all TETRAPODS 18. – 19. – 20. – 21. – 22. - Lungfish, Coelaanths, Ray-finned fish, Sharks and Jawless fish -530 mya a. These “fish” no more closely related to each other than they are to us b. MRCA of all VERTABRATES 23. – 24. – 25. – 26. Protosomes – around 600 mya a. >1 million described species 27. – 28. – 29. – 30. – 31. – 32. – 33. – 34. Fungi 35. Amoebozoans 36. Plants 37. – 38. Archaea 39. Bacteria 40. LUCA All life on earth is related through a common descent -we can trace our ancestry back to LUCA in just 39 steps -some similarities reflect shared ancestry (DNA, genes- inherited things) -other similarities reflect convergence (bee wings and bird wings- adaptations that are similar) Biology Midterm 1 Lecture 5 Why evolution is true The Dover trial  7-8 years ago  A school board took it upon themselves to teach the idea of evolution alongside the idea of intelligent design  These two ideas contradict each other (not helpful)  Intelligent design is not a scientific idea** Survey done asking if “humans evolved from earlier species of animals”  Many countries such as the United states, Turkey and Greece were at the bottom of this survey saying this statement was false  **not false**  Most people believe that god created humans in present form  People also believe that the controversy should also be taught (creatism) o This would be like going in circles o Example teaching that the pyramids were made by slaves or they could be made by aliens o Sense of ridiculousness Evolution as a fact and theory Evolution is “only a theory”  Theory means a coherent set of testable hypotheses that attempts to explain facts about the natural world  A scientific theory can be tested  We change theories to match the data (NOT the other way around)  Other scientific theories: o Atomic theory of matter o Germ theory of infectious disease o Gravitational theory What does it mean to say something is “true”  An assertion for which there is so much evidence that it would be perverse to deny it  We test a theory by attempting to falsify it  Theories graduate to fact hood after repeated testing fails to falsify them  We can’t prove things in the empirical sciences the way we can in math Biology Midterm 1 - If you can’t falsify a theory then it is not scientific  Russels teapot:  Said there is a teapot floating around in space but it is too small to see with a telescope Testing, debating and refining theories= the scientific process  These are all good things because science is always changing so we must revise to fit the data The theory of Evolution 1. Evolution Happens a. Allele frequencies in a population change from one generation to the next 2. Most evolution is gradual 3. Lineages diverge (speciate) into Gradual evolution multiple daughter lineages a. bacteria, archaea, eukaryotes, etc. (tree branches) 4. All life is related through common ancestry a. MRCA- most recent common ancestor 5. Much evolutionary change (not all) results from natural selection a. Example: adaptive change is evolutionary change b. Bottleneck effect IS NOT 6. Evolution occurs in a population; not in individuals a. Populations change but individuals do not adjust in response to selection Decent (from a common ancestor) with modification  sums up evolution  Homologies  Intermediates in fossil records  (requires) Old earth  Vestigial traits  Fossil evidence that species change  Fossil evidence that lineages split (speciate)  Direct observation of evolution in real time 1. Homologies (Decent)  Similar things that can’t be explained without saying they are from a common ancestor  Structural (diff bones in limbs), developmental (stages of embryo growth), molecular (codes for proteins) Biology Midterm 1 o Similarity between two species not explained by shared function, that reflects shared ancestry 2. Transitional forms “link” related groups (Decent)  Whale skull -50 mya- nostrils at front  Whale skull transitional- nostrils in center  Whale skull- present- nostrils on top 3. Evidence of Change (modification)  AZT-resistance  Can see the changes 4. Vestigial traits (modification)  Make sense only in the context of evolution  Organisms have certain traits that aren’t useful to them anymore  They have no function  Example: appendix, eyes of newt that always stays in the dark Summary of Evolution  Details of evolutionary theory continue to be revised, tested and falsified  When 2 opposite points of views are expressed with equal intensity, the truth does not always like exactly halfway between them. It is possible for one side to simply be wrong Biology Midterm 1 Lecture 6 Genome Structure and Variation Bridge: differences that matter  Differences that matter are usually in the DNA  Genetically heritable changes in DNA sequences o How do they get inherited? o What is variation and what is the origin? GENOMES Genome  Is all of the DNA sequence in one copy of an organisms chromosomes  DNA is in the nucleus, so it is called the Nuclear genome o DNA can also be found in the mitochondria and chloroplasts o They need to respire o Plants have 3 different genomes; nuclear, mitochondria and chloroplasts “C” value  Is the amount of DNA in one copy of a genome (“C”)  One C value is distributed over one set of chromosomes Domain Organisms Genome Size (Mb) Bacteria Carsonella 0.16 Escherichia (E.coli) 4.6 Archaea Thermoplasma 1.6 Methanosarcina 5.75 Eukarya Saccharomyces 12 Plants Orzya (rice) 430 Invertebrate Fruit fly 18 Vertebrate Homo sapiens 2900 **NOTICE: there are no trends when it comes to genome size**  Bacteria and archaea have smaller genomes but that is the only trend The “C” value enigma  “C” is not for complexity  Complexity and genome size are not related  Example. You would think humans have the most DNA or biggest genome but in fact salamanders and flat worms have more  Even organisms with more DNA don’t always have more chromosomes Type of chromosomes  Linear chromosomes are only found in Eukarya  Bacteria, Archaea, mitochondria and chloroplasts all have Circular chromosomes Biology Midterm 1 Chromosomes make you think of “X”  Chromosomes hardly ever look like “X”  Pictures show chromosomes as an “X” because it is the only time we can physically view them (Metaphase of Mitosis)  Chromosomes that DO look like “X” are replicated (after S phase) Chromosome  A chromosome is packed chromatin o DNA plus protein o Winding of the double helix around these nucleosite cores, packages them into chromatids o A packaged chromosome then appears as an X and is replicated **Human genome means: 23 chromosomes**  Because it is only ONE copy You can have 46 replicated chromatids or 46 unreplicated Ploidy (n) refers to the number of sets of chromosomes Diploid- 2 sets Triploid- 3 sets How many copies of the genome are represented in this karyotype? 4 Its 4c because “x” is replicated Human Genome project  2000- working draft from DNA to several anonymous donors  Mid 2000’s- individual sequences of Craig Ventor and James Watson  2010- individual sequences of different diversity’s  1000 genomes project currently underway What is your DNA sequencing?  Over half of your 3 billion base pairs do not code for you  Only 2% codes for you (essential)  Pseudo genes (dead genes), transposons- 55% Biology Midterm 1 Lecture 7 Before: 1. Purine and pyrimidine base-pairing in DNA/RNA DNA consists of four different nucleotides which consist of a 5 carbon deoxyribose group, a phosphate group, and one of four bases A-C-T-G. The purines consist of the two bases known as adenine and guanine which are nitrogenous bases built from a pair of fused rings of carbon and nitrogen atoms.  Pyrimidine consists of the two bases know and cytosine and thymine which are built from a single carbon ring. The number of purines equals the number of pyrimidine’s A=T, G=C [Chargaff’s rules] 2. Outcome of the classic Meselson and Stahl experiment the outcome of the classic Meelson and Stahl experiment was to demonstrate that DNA replication was semi-conservative. They figured this out by distinguishing parental DNA molecules from newly synthesized DNA molecules. 3. Direction of movement of DNA polymerase on the template strand Each DNA strand has two distinct ends consisting of a 5’ end and a 3’ end. DNA has an anti- parallel nature and therefore 5’ end is opposite of the 3’ end of the other. DNA polymerase can only add a nucleotide on a 3’ end of an existing nucleotide chain. As a new DNA strand is assembled, a 3’ hydroxyl group is always exposed at its newest end , the oldest end has an exposed 5’ phosphate. 4. Meaning of semi-conservative, semi-discontinuous, leading and lagging strand Semi-Conservative  Hydrogen bonds between two strands break allowing them to unwind and separate. Each strand then acts as a template for the synthesis of its partner. When replication is complete there are two double helices, each with one strand derived from parental molecule base-paired with a newly synthesized one. Each of the new two double helices consists of identical base-pair sequences as the parental DNA. Semi-Discontinuous  Descriptive of the replication of DNA in which the parent strand that is exposed from its 3'-end towards its 5'-end is used as a template for continuous synthesis of a new strand, but the parent strand that is exposed from its 5'-end towards its 3'-end is used as a template for synthesis of short discontinuous segments of DNA, called Okazaki fragments. These Okazaki fragments are covalently linked into a single continuous polynucleotide chain. Leading Strands: - Newly synthesized DNA strand made in the direction of DNA unwinding, which is created by leading strand template. Biology Midterm 1 Lagging Strands: -Strand synthesized discontinuously in the opposite direction is called the lagging strand, which is created by the lagging strand template. 5. General action of proteins in Fig. 12.15. Helicase – Unwinds DNA Helix. Primate – Assembles RNA primers in the 5’ TO 3’ direction. (New strand) SSBP – Stabilizes single stranded DNA to prevent the two strands at replication fork from winding back together Topoisomerase – Avoids twisting of DNA ahead of the replication fork (circular DNA) by cutting the DNA, turning the DNA on one side of the break in the direction opposite to that of the twisting force, and then rejoining. DNA Polymerase 3 – Main replication enzyme in E.COLi; extends RNA primer by adding DNA nucleotides to it DNA Polymerase 1 – E-coli enzyme that uses its 5’ to 3’ exonuclease activity to remove RNA of previously synthesized okazaki fragments and uses its 5’ to 3’ polymerization activity to replace RNA nucleotides with DNA nucleotides. Sliding Clamp- Tethers DNA Polymerase 3 to the DNA template making replication more efficient DNA Ligase – Seals nick left between adjacent bases after RNA primer replaced with DNA Genome replication Features of DNA  DNA has a double helix structure with 2 anti-parallel backbones  Has a distinct 3’-5’ end that confers “polarity” on DNA backbones  The 3’ end has a free hydroxyl and the 5’ end has a free phosphate o The 3’ end is where DNA polymerase adds to (ONLY THIS SIDE) **  DNA replication is semi-conservative because the daughters each have one old strand and one new strand  DNA is also semi-discontinuous o Replisomes replicate one strand continuously (leading strand) o They replicate the other strand discontinuously because it must constantly be re- primed (lagging strand) Prokaryotes have circular DNA o To replicate, a bubble arises from the two forks at one origin o They replicate bidirectionally and are also semi-conservative Biology Midterm 1 Note: the continuous (leading) strand depends on the origin and which way the fork is going o I.e. The top is not always the leading nor is the bottom always the lagging Linear DNA (eukaryotes) can also replicate using bubbles o In fact they create many bubbles to speed up the process because they have slower polymerases’ than prokaryotes When DNA replicates at S phase and enters G2 phase the 2 daughter cells create chromatid o The unreplicated structure and replicated structure are both considered ONE chromosome o Note: most cells are not dividing and stay in the G0 phase G1 chromosome is different than G2 chromosome structure ****** Biology Midterm 1 Lecture 8 Before: 1. Stages and main characteristics of the stages of mitosis. Mitosis is the division of cells in the creation of two daughter cells which contain an identical copy of chromosomes and genetic info as that of the parent cell. Mitosis occurs after the G2 phase which is the rest period for a cell. Mitosis can be divided into v
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