Bio - Genetics Notes PDF

BIO - GENETICS NOTES 2.1 MOLECULAR GENETICS GENETICS Study of heredity (birth) 3 BRANCHES OF GENETICS MOLECULAR GENETICS ○ Study of heredity at a molecular level ○ Mainly concerned with molecule DNA ○ Includes genetic engineering and cloning MENDELIAN GENETICS...

BIO - GENETICS NOTES 2.1 MOLECULAR GENETICS GENETICS Study of heredity (birth) 3 BRANCHES OF GENETICS MOLECULAR GENETICS ○ Study of heredity at a molecular level ○ Mainly concerned with molecule DNA ○ Includes genetic engineering and cloning MENDELIAN GENETICS ○ Study of heredity at the whole organism level by looking at how characteristics are inherited POPULATION GENETICS ○ Study of genetic differences within and between species ○ i.e. how species evolve by natural selection DNA Deoxyribonucleic acid Contains 3 components ○ Deoxyribonucleic sugar (5-carbon sugar) ○ Phosphate group (negatively charged) ○ Nitrogenous base NUCLEOTIDE ○ Molecules that consist of these components NITROGENOUS BASES PURINES ○ Two rings of carbon and nitrogen atoms ○ ADENINE and GUANINE PYRIMIDINES ○ Single ring of carbon and nitrogen atoms ○ CYTOSINE, THYMINE, URACIL ○ THYMINE is found in DNA only! ○ URACIL is found in RNA (ribonucleic acid) only! CONDENSATION REACTION Removal of water DIESTER BOND Linking 2 nucleotides together to form nucleotide polymers DNA and RNA GLYCOSYL BOND Bond between sugar and another organic molecule using an N or O STRUCTURE OF DNA DNA is double-stranded and strands are ANTIPARALLEL ANTIPARALLEL: they run in opposite directions (5’ → 3’ and 3’ → 5’) COMPLEMENTARY BASE PAIRS A and T are connected by TWO hydrogen bonds G and C are connected by THREE hydrogen bonds 2.2 - DNA REPLICATION + REPAIR SEMICONSERVATIVE REPLICATION Where DNA molecule is composed of one patent strand + one newly synthesized strand DNA replication is SEMICONSERVATIVE and not conservative REPLICATION ORIGIN When proteins bind at a specific site on the DNA HELICASE Unwinds the double helix by breaking hydrogen bonds REPLICATION FORK Y-shaped structure where DNA strands separate GYRASE Release tension on DNA to prevent it from snapping POLYMERASE I Removes RNA primers and replaces them with DNA POLYMERASE II Enzyme that builds the complementary strand using template strand as a guide Adds nucleotides and starts at 3’ then adds base pairs in a 5’ to 3’ direction RNA PRIMER Small section of RNA that provides a starting point for DNA polymerase RNA PRIMASE Hold that spot to allow polymerase 3’ to attach LEADING STRAND Strand of DNA that is synthesized continuously in 3’ to 5’ direction LAGGING STRAND Strand that is synthesized discontinuously in short fragments OKAZAKI FRAGMENTS Short DNA fragments that are synthesized in the lagging strand Polymerase I removes primers from the leading strand + replaces them with appropriate deoxyribonucleotides LIGASE Joins the Okazaki fragments together to form a continuous DNA strand EXONUCLEASE Corrects and continues adding nucleotides to the complementary strand TOPOISOMERASE Relieves torsional strain ahead of the replication fork SINGLE-STRAND BINDING PROTEIN (SSBS) A protein that keeps separated strands of DNA apart REPLICATION BUBBLE Where two replication forks are close to each other, producing a bubble POLYMERASE II Enzyme that adds nucleotides to the new DNA strand, using original strand as a template PHOSPHODIESTER BOND Bond that forms between nucleotides to construct RNA and DNA DEOXYRIBONUCLEOSIDE TRIPHOSPHATE (DNT) Nucleoside with 3 phosphates IMAGE 2.3 - AGING TELOMERES Long sequences of repetitive, non-coding DNA on the end of chromosomes  Common base code found on one end of strand of DNA is 5’ - TTAGGG - 3’ FUNCTION OF TELOMERES Help prevent chromosome ends from fusing to other chromosomes Prevent DNA degradations from enzymes (nucleases) Assist DNA repair mechanisms in finding DNA breaks from chromosomal ends LIFESPAN: plays a role in determining the number of times a cell can divide SENESCENCE CELL SENESCENCE: where a nucleotide loses its ability to function properly ○ Leads to loss of function as we age ○ Ex. GROWTH, METABOLISM, GENES HAYFLICK LIMIT: how long cells have before they DIE GERM CELLS TELOMERASE: an enzyme that adds more DNA to shorten telomeres, continually restoring the length PROGERIA Genetic disorder where children age up to 10x the speed of “normal” people PCD - program cell death (APOPTOSIS) Their cells go through apoptosis fast PLEIOTROPIC GENES A gene that has a two-prong produce Helps when you’re YOUNG → hurts when you’re OLD Gets humans to REPRODUCTIVE age 2.4 - PROTEIN SYNTHESIS BACKGROUND To initiate PROTEIN SYNTHESIS ○ Genes are first transcribed into an RNA complement ○ RNA is then translated by ribosomes into proteins ○ If certain protein is in high demand, numerous RNA transcripts of its gene will be produced GENES A sequence of nucleotides in DNA ○ Composed of letters (ATCG); turns into AMINO ACIDS  ○ Direct production of proteins that determine the physical characteristics of organisms PROTEINS polypeptide chains of amino acids folded together (ALL ENZYMES ARE PROTEINS) Drive CELLULAR PRODUCTION (such as metabolism) Determine physical characteristics Manifest genetic disorders by their absence or presence in an altered form GARROD’S HYPOTHESIS Studied with people with “ALKAPTONURIA” ALKAPTONURIA: a disease where urine turns black b/c it contains alkapton Hypothesized that people with alkaptonuria had a defective enzyme that can't break down alkapton CENTRAL DOGMA DNA is transcribed by a messenger RNA (mRNA) mRNA leaves the nucleus to deliver the genetic information to ribosomes Ribosomes then translate the message into polypeptide chains, creating proteins TRANSCRIPTION: involves the copying of the information in DNA into mRNA TRANSLATION: involves ribosomes using the mRNA as a blueprint to synthesize a protein composed of amino acids RIBONUCLEIC ACID (RNA) Has sugar ribose instead of deoxyribose; SAME phosphate, SAME base Base = URACIL (AUGC) Single-stranded Shorter than DNA Resides outside the nucleus 5 CARBON GROUP 5’ - connects the phosphate group 3’ - hydroxyl group 1’ - glycosyl group  Carbon 2’ has a carbon in RNA but none in DNA CLASSES OF RNA mRNA ○ Carries the “message” that codes for a particular protein from the nucleus ○ Makes a copy and brings it to ribosomes ○ Single-stranded + long enough to contain one gene ○ Short lifetime and is degraded after used rRNA ○ Ribosomal RNA ○ Helps make ribosomes ○ Provides the construction site for the assembly of polypeptides ○ Varies in length tRNA ○ Transfer RNA ○ Has cloverleaf structure ○ Contains one amino acid ○ Transfers the appropriate amino acid to ribosome to build a protein TRANSCRIPTION Process where DNA is used as a template for production of complementary messenger RNA molecules INITIATION: RNA polymerase connects to the promoter region and splits RNA ELONGATION: RNA polymerase puts together appropriate ribonucleotides and builds mRNA transcripts TERMINATION: RNA reaches a STOP, exits the nucleus and mRNA separates INTRONS: ○ interruption sequences ○ Non-coding regions ○ Removed before the mRNA leaves the nucleus b/c it’s USELESS, the information does not need to be transcribed + will make mRNA more compact for protein to fold TRANSLATION process where a ribosome assembles amino acids in a specific sequence to synthesize a polypeptide coded by mRNA INITIATION: ○ ribosome clamps on mRNA + moves down to find a starting code  ○ If start code (AUG) is not found, mRNA won’t translate + stops once it finds code ○ Code is 3 letters long ELONGATION: ○ tRNA delivers amino acid ○ Starts to build appropriate polypeptide chain TERMINATION: ○ When codon “stops” the ribosome will unclamp from RNA + chain is released ○ Translation is complete CODON: ONE codon = ONE amino acid ○ Set of THREE nucleotides GENETIC CODE Linear code and can only be read in one direction (5’ → 3’) Codes cannot OVERLAP It’s a UNIVERSAL CODE: there is a ‘start’ signal and three ‘stop’ signals PUNCTUATION CODES: ‘start’ signal = AUG (Met - Methionine) ‘stop’ signal = UAA, UAG, UGA TAC is complementary to AUG Ex. UUU = Phe UCU = Ser CGG = Pro 2.5 - TRANSCRIPTION TRANSCRIPTION starts when enzyme RNA POLYMERASE binds to segments of DNA that are transcribed + open double region 1. INITIATION PROMOTER REGION: sequence of DNA that binds RNA polymerase upstream of a gene UPSTREAM REGION: sequence on one strand of DNA ○ Located before the start of a gene TATA BOX: section with many thymines in a row Takes less energy to break, b/c TWO hydrogen bonds between them UTR (UNTRANSLATED REGION): area before a gene + guides them 2. ELONGATION RNA polymerase builds single-stranded mRNA in the direction of 5’ → 3’ Starts as soon as RNA polymerase moves to start of gene + binds to promoter TEMPLATE STRAND: chosen strand ○ Goes from 3’ → 5’ ○ Complementary to RNA CODING STRAND: strand that is not used ○ Identical to RNA (except for U and A) ○ Goes from 5’ → 3’ 3. TERMINATION RNA reaches a TERMINATOR SEQUENCE and breaks off the gene Can go back to the beginning + make more RNA proteins TRANSCRIPTION ceases + RNA polymerase is free to bind onto another promoter region and transcribe to another gene POST-TRANSCRIPTIONAL MODIFICATION 4. 5’ CAP (CAPPING): 7-methyl guanosine added to start of primary transcript - Protects mRNA from digestion POLY-A-POLYMERASE: adds a string of adenine bases to end of mRNA ○ Protects it from degradation POLY-A-TAIL: a string of 200-300 adenine base pairs at the end of mRNA transcript ○ INTRONS: interruption sequences (removed from mRNA) Non-coding region of a gene ○ EXONS: expressed sequences (pushed together) Segments of DNA that code for part of a specific protein 5. SPLICEOSOMES (SPLICING): complex formed between pre-mRNA Contains a handful of small-ribonucleoproteins (snRNP) ○ mRNA TRANSCRIPT: mRNA that has been modified to be translated by a ribosome into protein 2.6 - TRANSLATION TRANSFER RNA Translate mRNA into polypeptide Correct amino acid must be delivered to the polypeptide-building site tRNA: molecule that delivers the amino acid  Translation does not occur until it reads AUG AUG ensures that the correct reading frame is used by the ribosomes tRNA mRNA = 5’ → 3’ tRNA = 3’ → 5’ ANTICODON: group of three complementary bases on tRNA Recognizes and pairs with codon on mRNA Tip of tRNA 61 bases can be made, but there are NOT 61 different tRNA Some tRNAs code for more than one codon WOBBLE HYPOTHESIS: third nucleotide is not as important as the FIRST TWO ○ Ex. UAU and UAC = tyrosine ○ Third base of a codon TRANSFER RNA AMINOACYL-tRNA: amino acid that is attached to the 3’ end AMINOACYL-tRNA SYNTHASE: enzyme responsible for adding the appropriate amino acid to each tRNA THE RIBOSOME INITIATION ○ Ribosome clamps onto the mRNA + starts the reading frame ○ Starts on the front; the 5’ code will help to clamp ○ READING FRAME: ribosomes move along mRNA from 5’ → 3’ + add new amino acids to growing polypeptide chain when it reads a codon ELONGATION: ○ A SITE (AMINOACYL or ACCEPTOR) - where the incoming aminoacyl tRNA is added ○ P SITE (PEPTIDYL) - where the tRNA carrying the growing polypeptide (protein) chain is bound ○ E SITE (EXIT) where empty tRNA leaves ribosome + picks up another amino acid top of tRNA will be cleaved (no amino acid attaches to tRNA) 6. INITIATION Codon AUG (on mRNA) starts every polypeptide chain as it codes for METHIONINE met-tRNA binds behind the 5’ cap SCANNING: process where ribosome complex moves along the mRNA 7. ELONGATION Once met-tRNA is in P site and A site is empty the second tRNA can bind to A site (like a never-ending chain) Bonds between MET and second amino acid are catalyzed by PEPTIDYL TRANSFERASE MET is now cleared from tRNA and is moved into the E site 8. TERMINATION Ribosome will eventually reach a “stop” codon RELEASE FACTOR: protein that recognizes the ribosome has stalled + aids in the release of a polypeptide chain from ribosome Single piece of mRNA can be translated by many ribosomes POLYSOME: group of ribosomes all attached to one piece of mRNA POST-TRANSLATIONAL MODIFICATIONS Modifications include: ○ 9. CHAINCUTTING: adding methyl or phosphate groups to amino acids ○ 10. Adding sugar to protein to make GLYCOPROTEINS and adding lipids to make LIPOPROTEINS 2.7 - CONTROL MECHANISMS AND MUTATIONS GENES HOUSEKEEPING GENES: genes that are always needed and are constantly being made TRANSCRIPTION FACTORS: ○ proteins that turn genes on when required, by binding to DNA ○ helps the RNA polymerase to bind ○ Tells when a gene should be turned or transcribed GENE REGULATION 4 levels of CONTROL ○ TRANSCRIPTIONAL: regulates which genes (DNA-mRNA) are transcribed ○ POST-TRANSCRIPTIONAL: which introns and exons are spliced ○ TRANSLATIONAL: controls how often/fast mRNA transcripts will be translated into proteins ○ POST-TRANSLATIONAL:  proteins must pass through the cell membrane to be functional Affects the rate at which they become active MUTATIONS SINGLE-GENE MUTATIONS: involve changes in the nucleotide sequence of ONE gene CHROMOSOME MUTATIONS: ○ Involve changes in chromosomes ○ May involve MANY genes TYPES OF MUTATIONS SOMATIC CELL: ○ Organisms will go unnoticed unless a large number of cells are involved ○ Not passed on to next generation ○ Mutation is SOMATIC CELL will go in some cells GAMETIC CELL: ○ Can be passed onto offspring ○ Mutation in GAMETIC CELL will go in every single cell POINT MUTATION: where ONE base gets changed ○ SILENT MUTATION - Mutation that does not result in change in amino acid - Does not cause any phenotype change - Where one base has changed, amino acid stays the same; intron gets changed - UUU and UUC → both code for Phe ○ MISSENSE MUTATION - When a change in the base sequence of DNA changes a codon, leading to different amino acids are placed in the protein sequence - Where single base is changed, changes amino acid, causing the protein to fold - Beneficial in making new antibodies ○ NONSENSE MUTATION - When a change in DNA sequence causes a STOP-CODON to replace a codon making an amino acid - A single base changed, then turns into PREMATURE STOP-CODON FRAMESHIFT MUTATIONS DELETION ○ Occurs when one or more nucleotides are removed from the DNA sequence ○ Protein can be drastically changed + will result in defective protein ○ Shifts to the LEFT ex. AUG / GGA / UUC / AAC AUG / GAU / UCA / AC INSERTION ○ Placement of an extra nucleotide in a DNA sequence ○ Shifts to the RIGHT TRANSLOCATION Relocation of groups of base pairs from one part of genome to another Occurs b/c TWO nonhomologous chromosomes Happens before zygote is made Segment of chromosome breaks + releases a fragment ○ Same fragment takes place with another chromosome CROSSING OVER: chromosome from mom and dad - Before they make sperm, chromosome switches in prophase DELETION AND DUPLICATION DELETION: part of chromosome is GONE DUPLICATION: getting extra chromosomes is NOT GOOD CAUSES OF MUTATIONS SPONTANEOUS MUTATIONS: ○ Occurs without chemical change or radiation, but errors made in DNA replication ○ OUT of our control MUTAGENIC MUTATIONS: ○ Agents that can cause a mutation ○ IN our control (ex. UV rays, benzene, nuclear energy) CANCER Loss of regulatory mechanisms which control cell growth + differentiation DIFFERENTIATION: repressed or imperfect PROLIFERATION: genes that are left on (stop the cell from progressing) OPERONS OPERON ○ cluster of genes under control on one promoter + one operator in prokaryotic cells ○ OPERATOR: regulatory sequence of DNA where a repressor protein binds ○ Acts as a regulatory loop LAC OPERON Cluster of THREE genes that code for proteins in metabolism of lactose Three genes: ○ lacZ: encodes the enzyme B-galactosidase ○ lacY: encodes B-galactosidase permease ○ lacA: encodes a transacetylase of unknown function LACI PROTEIN ○ repressor protein that blocks transcription of B-galactosidase gene from binding to lactose operator + getting in the way of RNA polymerase ○ Binds to operator when lactose levels are LOW When lactose is not present, Lacl protein binds to lac operator, covering the promoter which blocks transcription High levels of lactose induce the operon TRP OPERON Regulates the production of amino acid TRYPTOPHAN Consists of cluster of FIVE genes under control of one promoter + one operator ○ Genes are five polypeptides that make enzymes to synthesize tryptophan Corepressor tryptophan binds to trp repressor protein ○ Binds to operator when tryptophan levels are HIGH High levels of tryptophan repress the operon