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Bio 1001 Midterm Study Notes.pdf

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Biology 1001A
Tom Haffie

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Biology 1001 Midterm Review HIV • Becoming Global Pandemic • Estimated 33 million people affected worldwide • Very Common in Sub Sahara Africa How do Viruses replicate? • Adhesion, infiltration of host cell • Injection of viral genome • Hijacking of host cell machinery to create new viral particles Retrovirus • HIV is a retro virus Means has a RNA genome • • RNA must be Reverse Transcribed into DNA once in host cell • Enzyme “Reverse Transcriptase” target for anti viral • AZT, inhibits “Reverse Transcriptase” AZT Therapy • Resistance can develop • Over time becomes less effective “cocktail” of drugs given to avoid total resistance • • CCR5 allele, natural human resistance? Origins of Life: 3 Stages of Prebiotic Evolution 1.Geophysical Stage • Primordial Earth had a reducing atmosphere composed of water vapour, hydrogen, methane, ammonia, and hydrogen sulfide • The surface of primordial Earth was chaotic, constant lightening storms, bombardment of space material • Early life formed around 3.5 billion years ago •Cyanobacteria • Suggests Life arose very quickly and easily on Earth! 2.Chemical Stage • the Miller-Urey experiment • Primordial Earth provided sufficient elements (in gases) and energy (lightning) to produce amino acids • Reducing atmosphere, not able to break these molecules apart • Chirality • Most amino acids are chiral, abiotic synthesis of amino acids does not favour a particular enantiomer. • Chirality of molecule is important! (Thalidomide) 3. Biological Stage • Needs information storage molecules (DNA / RNA) and way to express information (Protein) • Clay was found to help the polymerization of amino acids • Rybozymes were the “missing link”; they can store information and be catalytic. • Eventually, RNA shifted to DNA because of increased stability. Central Dogma? • DNA  RNA  protein • RNA has both information storage ability, and enzymatic activity • DNA  RNA  Protein (likely started with RNA) Biodiversity • LUCA (Last Universal Common Ancestor) (origin of life) • Many different branching points along the evolution of species • We did not “descend from chimps”, us and chimps shared a common ancestor many years ago. • ~ 63 mya MCRA for all primates Some traits similar between species due to common ancestor • • Some due to sharing similar environments over time • “Convergent evolution” Lecture 5: Genomic Structure and Variation The Genome • The amount of DNA in one genome is called “C”. It’s measured in Million bases (Mb) • The DNA sequence in one copy of an organism’s chromosomes (n) not (2n) One C-value is distributed over one set of chromosomes (n) • • Haploid (n) is one copy of chromosomes, Diploid (2n) is two copies of chromosomes • Reminder * A plant cell has three genomes (nuclear, mitochondrial, chloroplast) Diploid Karyotype The C-value Enigma • Mystery of the extensive variation in nuclear genome size within a taxonomic group • Genome size does not correlate with organismal complexity; E.g. some single-celled protists have genomes much larger than that of humans. • prokaryotes: everything but eubacteria and archea • eukaryotes: archea and eubacteria Circular chromosomes is Ancestral • Mitochondria and chloroplasts have circular chromosomes • It is thought that the Last Universal Common Ancestor had circular chromosomes Ploidy Number of sets of chromosomes • • Haploid: One copy • Diploid: Two copies • Triploid: Three copies • Tetraploid: Four copies Packaging DNA • Chromatin: DNA + Proteins • Chromosome: Packaged chromatin The Replicated Chromosome • A chromatid is one of the two copies of DNA making up a duplicated chromosome, which are joined at their centromeres • The number of chromosomes does not change during S phase (n does not change, C value doubles) Your DNA sequence is mostly junk • only 10% contributes to you Genome Replication • The two strands run antiparallel • A=T, CΞG Pyrimidines: A, T Purines: C, G • Replication goes from 5’ -->3’ • DNA Polymerase always adds to the 3’ end*** • Semiconservative: Each strand is used as a template to make a new strand • decrease chances of replication errors--> enzymes can check for errors using the ‘old’ strand (template strand) Terminology Replisomes carry out DNA replication. A replisome is composed of many proteins e.g. DNA polymerase, helicase, ligase, etc. It is active at the replication fork. It contains 2 molecules of DNA polymerase, to simultaneously replicate both strands of the helix (one continuously and one discontinuously) DNA helicase “unzips” (cuts the hydrogen bonds) between bases of a strand of DNA producing replication forks DNA polymerase codes from the 5’ (phosphate) to 3’(OH) end, adding appropriate bases One strand is replicated continuously, one is replicated in fragments The strand replicated in fragments is called the lagging strand There are 2 common methods to correct replication errors: • proofreading: DNA polymerase will detect and fix base-pair mismatches excision repair: proteins will recognize errors in physical structures of the strand and cut out that portion of the new chain (includes the mismatch pair) MUST BE ABLE TO DRAW FROM SCRATCH The lagging strand • DNA Polymerase always builds from 5’--> 3’. It builds from the free OH group. RNA Primers provide this OH group • RNA Primers are removed, and the free 3’ OH groups at the end of the DNA fragments provide starting places for replacing the RNA with DNA • At the end of the chromosome, there is no 3’ hydroxyl group available to prime DNA synthesis • Chromosomes would start to shorten after each replication cycle! This problem is solved by telomerase The ends of chromosomes contain a G rich series of repeats called a telomere. Telomerase recognizes the tip of an existing repeat sequence. Its RNA template binds to the DNA telomere. Using an RNA template within the enzyme, Telomerase elongates the parental strand in the 5’ to 3’ direction, and adds additional repeats as it moves down the parental strand. Telomerase adding additional repeats of telomeres to the parental strand... A primer can bind to the end, andDNA polymerase 1 can elongatethe strand to ensure no information is lost from chromosomes Telomerase Continued • telomerase is most active in gametogenesis, highly cycling cells, and cancer cells. Telomerase is not expressed in cells that are not actively cycling (most somatic cells) • Over time, due to each cell division, telomeres become shorter in somatic cells->leads to aging. When telomeres get too short, this signals apoptosis (telomeres tell a cell how old it is) • Telomeres are only found in linear DNA, so prokaryotes don’t have this end replication problem! telomerase shown in red Check out this youtube video if still confused: Telomere Replication Inheritance of Sameness Mechanisms to Ensure Sameness 1. Complementary base pairing during replication 2. Old cells die 3. Cell cycle checkpoints to ensure accurate progression through the cell cycle Centromere and Telomere • Highly repetitive, non coding, structural DNA sequence --> not junk Kinetochore • The kinetochore is the protein structure on chromatids where the spindle fibers interact during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. Cell Cycle Checkpoints • There are checkpoints that will control rate of cycling and if cell will go through cell cycle: 1. G1 (Restriction) Checkpoint: The checkpoint located at the end of the cell cycle's G1 phase, just before entry into S phase, making the decision of whether a cell should divide or enter G0. 2. G2-M Checkpoint: Ensures that cells don't initiate mitosis before they have had a chance to repair damaged DNA after 3. Metaphase Checkpoint: Cell will not divide until chromosomes are attached to microtubules and aligned properly • Most cells are in G0. Cells in G0 can be stimulated back into cell cycle Origin of Variation SNPs • Single Nucleotide Polymorphisms: DNA sequence variation occurring when a single nucleotide differs CNVs • Copy Number Variants: alterations of the DNA of a genome that results in the cell having an abnormal number of copies of one or more sections of the DNA • Affect thousands of nucleotides, in contrast to SNPs that affect one nucleotide 2 copies of the same section Transposable Elements • Segments of DNA that move from one genomic location to another (“Jumpin
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