ALL of BIOL190 Lecture Notes
ALL of BIOL190 Lecture Notes BIOL 190
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BIOL190 Biology for Health Professions Dr Shah Fall 2015 Lecture Notes Lectures 124 DNA and Gene Expression Lecture 14 Deoxyribonucleic Acid DNA 0 2 nucleotide strands twisted into a double helix 0 Each strand is made up of repeating nucleotide subunits 0 Each nucleotide contains a phosphate group P04 glucose nitrogen base 0 Strands oriented in opposite directions antiparallel o BasePairs link strands to each other big base small base 0 Hydrogen Bond 0 AT 2 bonds and GC 3 bonds Bases in DNA 0 Adenine A Guanine G Purines Big DoubleRing Thymine T Cytosine C Pyrimidines Small SingleRing Sugar Phosphate backbone directly held together with strong covalent bonds Neighboring Bases are NOT directly linked by the sugar phosphate backbone DNA is a doublestranded molecule where each strand is a chain of nucleotides 0000 Hershey and Chase Experiment 0 De nitive demonstration that DNA is the genetic material 0 Used a bacterial virus called T2 Phage bacteriophage that reproduces by infecting bacterial cells Ecoi and the infection proceeded even if virus particles shaken off blender after brief attachment period c How the experiment was carried out 0 Prepared 2 separate batches of virus radioactively label DNA CHONP or Protein CHONS 0 Method 0 Virus radioactive DNA 32p Protein 35S o l Infected bacterial cells 0 2 Blender shake off parts of virus that didn t enter cells quotvirus leftovers o 3 Centrifuge cells pellet virus leftovers liquid 0 Centrifugation extended forces will be drawn down example sand and water 0 Results The pellet after centrifugation contains heavier bacterial cells showed radioactive phosphorous labeled DNA 32p 0 Conclusion since radioactive phosphorous was detected in bacterial cells pellet It suggests that DNA was internalized in bacterial cells and hence DNA is the genetic material 0 DNA must have entered into heavier bacterial cells 0 35S was found in the liquid so T2 Phage proteins must have stayed outside cells Watson and Crick Made a 3D model of DNA 0 Strand Polarity 5 P04 end 3 sugar end 0 Rosalind Franklin and Maurice Wilkens XRay Diffraction of DNA From measurement Purines and Pyrimidines must be paired together to keep constant 2 nm helix width 0 Erwin Chargaff chemical analysis of DNA 0 Amounts of AT GC in any as DNA sample 0 Order of AT GC differed across samples 0 Proportions of AT GC differed in samples DNA Replication 2 ways cells use the genetic info stored in DNA 1 Control DNA controls cell structure function Transcription and Translation 0 Codes directly for all proteins in cells 0 Proteome speci c array of proteins in a given cell determines cell makeup and what jobs it can do ex Carry 02 red blood cells ght disease white cells contrast muscle cells 2 Heredity complete copy of genetic info physically passed from generation Replication 0 DNA must be copied replicated replication of DNA 0 DNA copies passed on to offspring from 2 parents in sexual reproduction o Inherited through generations 0 DNA replication part of HEREDlTY function of DNA 0 Cell division 1 parent cell 2 daughter cells OOOO Daughter cells are genetically identical to parent cell Must copy cell s DNA l 2 copies copying occurs in SPhase of cell cycle DNA Replication is SemiConservative Parental molecule in split in half with daughter DNA Replication the parental strands separate and serve as templates and 2 identical daughter molecules of DNA are formed DNA replication is semiconservative OOOOOOO Covalently linked by DNA Polymerase enzyme At origins DNA Strands begin to unwind and separate with the help from Helicase enzyme DNA Polymerase can ONLY add new nucleotides at 3 end direction is always 5 to 3 Separate fragments need to be linked ligated together covalently by DNA Ligase enzyme Lagging Strand new strand is made 5 3 Leading Strand leading the synthesis First thing in DNA replication is to unwind the strand with the enzyme Helicase DNA Polymerase which helps join the nucleotides during complementary pairing links them covalently synthesis in the 5 3 and Ligase joins molecule Proofreading DNA Polymerase O O O Removes any incorrect base pairing Errors that remain Gene mutations Mutation Permanent change in the DNA Base sequence Gene Expression control role of DNA RNA In uence of genetic info in DNA on cell structure and function 0 0 Through production of PROTEINS that make up the structure and carry out the function of the cell Proteins are coded for by genes segment of DNA in chromosomes Control role of DNA is NOT related to the heredity role of DNA Genes segments of the DNA in each chromosome 0 O 0 Each chromosome has a different set of genes often separated by noncoding regions of DNA Each gene codes for a speci c gene product in the cell mostly protein some RNA Which part of the DNA structure carries the code Sequence of Bases Requires 2 Processes O 0 DNA Transcription copying of DNA info into RNA copies Used to make mRNA tRNA rRNA takes place in the nucleus where DNA is Final RNA products then go to the cytoplasm mRNA Translation interpretation of mRNA code synthesis of protein take place in the cytoplasm involves mRNA message tRNA interpretation and ribosomes rRNA and ribosomal proteins Sugar ribose Bases A U G C no T Single stranded DNA Replication DNA Transcription Occurs in synthesis S phase of cell cycle Occurs in preparation phase of cell cycle G1 and G2 Enzyme DNA Polymerase Enzyme RNA Polymerase Both strands of DNA are template One strand of DNA is template Utilizes nucleotides ATGC Utilizes nucleotides AUGC Entire genome copied Only individual genes transcribed Product formed remains bound to parent DNA molecule Products formed detach from DNA and goes to cytoplasm Steps of DNA Transcription RNA Polymerase binds at 39promoter region of TEMPLATE strand of gene RNA polymerase unwinds DNA locally as it moves along template no helicase needed Free RNA type nucleotide covalently to 3 end of growing RNA molecule RNA made in 5 3 direction 0 Process stops at terminator region RNA comes off many more copies made DNA comes back together and rewinds into helix RNA goes to the cytoplasm through nuclear pore ONLY a GIVEN GENE TRANSCIRBED NOT WHOLE GENOME DNA Coding Each gene codes for a speci c product molecule 0 A few genes code ribosomal RNA rRNA Several genes code for transfer RNA tRNA All other genes code for messenger RNA mRNA and each mRNA codes for a speci c protein mRNA tRNA rRNA all made by DNA transcription mRNA tRNA rRNA all needed for protein synthesis mRNA Translation 0000 mRNA messenger RNA 0 Each mRNA molecule made by DNA transcription of a particular protein coding gene in nucleus Processed in nucleus 0 5 cap modi ed G and 3 tail sequence polyA tail added for mRNA 0 lntrons spacer regions cut out o Exons expressed regions spliced together Goes out to the cytoplasm o Brings the genetic info from one proteincoding gene to the cytoplasm o Coding units 39codon tRNA transfer RNA otRNA molecule made by DNA transcription of tRNA coding genes in nucleus Go out to the cytoplasm Appropriate amino acid then attached to each tRNA at its amino acid binding site Requires a speci c loading enzyme and ATP energy Anticodon of each tRNA complementary to speci c codon in mRNA oBasePairing of anticodon and codon allow tRNA to deliver amino acid to correct place during translation rRNA ribosomal RNA rRNA molecule made by DNA transcription from particular rRNAcoding genes in nucleus speci c rRNA molecules then assembles with speci c ribosomal proteins brought in from cytoplasm to form 2 subunits of ribosomes Large and small ribosomal subunits CodonSeouence of 3 Adiacent Nucleotides on a Strand Constitutes genetic code for speci c amino acid that is to be added to polypeptide chain Codon Chart mRNA 0 Speci c but 0 Redundantsame amino acid that is to be added to polypeptide chain 0 AUG start amino acid met methionine o UAA UAGUGA STOP Codon to terminate protein synthesis Given an mRNA sequence how do you translate it 0 Use the genetic code 0 Record abbreviation of amino acid 0 Find the start codon STOP when you reach a stop codon 0 Mark off the triplet code 0 DO NOT do anything with anticodons Look up each codon in mRNA in the dictionary 0 Example CGUCUAUGUAUGGCCAUGCCCCAUGAUACGl met tyr gly his ala pro STOP Translation Protein Svnthesis Nucleic acid language to protein language lnitiation Elongation Termination Translation Initiation Formation of functioning complex 0 1st initiator met loaded tRNA binds to small ribosomal subunit Small ribosomal subunit and tRNA met binds to beginning of mRNA Small ribosomal subunit moves along mRNA until start codon AUG Stops there bc UAC anticodon on tRNA met base pairs with AUG in mRNA Large ribosomal subunit then joins complex A site is open ready for tRNA called for by codon in the A site 00000 Translation Elongation codonanticodon interaction Next tRNA amino acid diffuses in with its amino acid to dock at the next codon A site Correct tRNA amino acid comes in bc its anticodon is complementary to codon in A site Previously added amino acid breaks off of the tRNA that brought it in and links covalently to the next amino acid 0 This is the actual synthesis step catalyzed by peptidyl transfer enzyme in large ribosomal subunt The now empty tRNA in the P site diffuses away will be reloaded for next job Ribosome moves along mRNA to the next codon translocation Process repeats itself Translation Termination At stop codon 0 Release factor binds to stop codon signaling end of translation 0 Complex disassembles nished protein released into cell empty tRNA falls out of the complexwill be reloaded for the next job ribosomal subunits come apart will be reused for further protein synthesis Further ribosomes have come behind the rst make more copies of the same protein Protein Enzvme Function One of major function of protein serves as enzymes 0 Enzymes speed up chemical reactions 0 Required for chemical reactions to run at body tempt in the cell Ex chemical reaction to make RNA during DNA transcription lf RNA polymerase gene is mutated it may not be expressed properly or at all so no functional enzyme made DNA codes for protein enzymeslj presenceabsence of lipidscarbs indirectly control over these molecules 0 How can oene exoression chanoe in cells 0 Level of 0 Name 0 Reversibility 0 Description change 0 Using vs not 0 Regulation of gene 0 Reversible 0 Cell can turn using the info expression normal expression of process in cells genes onoff depending on need conditions Changing the o Mutation result of 0 Not reversible o Mutation is a info errorsdamage once permanent proofreading change in the step is nished base sequence Francis lacob and lacques Monod Observed bacteria Ecoi and noticed that o If the nutrient sugar lactose was added to cells nutrient medium all 3 enzymes needed for it use appeared in the cells o If lactose was absent all 3 enzymes were absent 0 Lactose seemed to be quotturning onquot 0 Control of the 3 genes seemed to be coordinated Proposed the idea of an operon 0 Segment of DNA in bacteria that includes promoter sequence where RNA polymerase binds operator sequence where a repressor protein binds a group of structural protein coding genes Gene Mutation Permanent change in the base sequence of DNA in one gene region Leads to mistakes in RNA protein encoding What are the 2 ways gene mutation can arise 0 DNA replication error not corrected by proofreading 0 Environmental mutagens radiation chemicals viruses When in the cell cycle would each of these be most likely to occur 0 Proofreading error S during DNA Replication 0 Environment damage throughout the cycle Biomolecules Lecture 58 Proteins functional catedories Transport movement of materials around body or intoout of cells 0 Potassium channel facilitates movement of charged K ions across membrane 0 Hemoglobin in red blood cellscarries oxygen from lungs to body cells Hormones chemical signaling in the body 0 Insulin glucagon regulate blood sugar levels Contractile contraction o Actin myosin muscle contraction Structural structural support toughness o Collagen in extracellular matrix around the cell 0 Keratin epidermal layer Protection 0 Antibodies immunity in white blood cells Enzyme needed to facilitate every reaction in the body 0 Trypsin digests proteins in the small intestines o Amylase digests starch in the saliva Storage nutrient storage for growing embryo o Endosperm proteins in seeds Protein monomers amino acids Amino group central carbon hydrogen atom carboxyl group Mass of 1 amino acid measured in Dalton Rgroup also called side chains variable groups How do the R groups vary 0 Size a single hydrogen to a long chain bulky ring structure 0 Charge or or neutral 0 Polarity partial charge on an atom resulting of unequal sharing of electrons Water Solubility 0 Charges and polar R groups hydrophilic water soluble o Uncharged and nonpolar R group hydrophobic not water soluble Formation of a covalent peptide bond between 2 amino acids to form a chain polvoeptide This chemical reaction is called Dehydration Synthesis 0 Removal of OH from one amino acid and H from other amino acid releasing a H20 molecule 0 Allows direct covalent linkage between 2 amino acids 0 So water is taken out dehydration as a larger molecule is made The covalent bond between two amino acids monomers in a polypeptide polymer PEPTIDE BOND Dehydration synthesis to make a polypeptide chain is translation Polypeptide a chain of amino acids produced by dehydration synthesistranslation Primary 1 Structure Linear chain of amino acids held together in a sequence by covalent bonds from dehydration synthesis What determines the speci c order of amino acids in the chain 0 mRNA translation Secondary 2 Structure Distribution of alpha helices and beta pleated sheets along a protein chain Spatial arrangement of amino acids residues that are nearby in sequencelocal regions of the polypeptide chain Regular coils helices and folds pleated sheets with connected segments Hydrogen bonds between part of backbone R group NOT involved Tertiarv 3 Structure Overall 3D shape where 2 structure folded into a 3D shape Refers to the spatial arrangement of amino acid residues that are far apart in the sequence and to the pattern of disul de bonds covalent protein Hydrophobic interactions always on the inside of the protein with no interact H20 Quaternarv 4 Structure Refers to the spatial arrangement of subunits and the nature of their interactions Functional proteins consisting of more than 1 individual polypeptide chain Polypeptide 0 Protein Linear chain of amino acid chain with o coilingfolding which has NOT acquired normal 3D shape required for its function 1 ore more polypeptides with appropriate levels of structure to make it able to function Polypeptide chain can NOT perform 0 Gives native conformation of proteins functional in the cells 0 Normal form structure 0 Can perform function in the cells Non polar R groups internalize to minimize interaction with water Polar and charged R groups position themselves 0 On the exterior where they will interact with water be in positions to interact with each other What stabilizes 3 structure 0 Hydrophobic interaction Hydrogen Bond Disul de Bond lonic Bond Proteins Glucagon functional at 2 structure pancreatic hormone raises blood sugar if the level gets too low Amylase functional at 3 structure enzyme that hydrolyzes starch in the mouth saliva Hexokinase functional at 3 structure enzyme that catalyzes the rst reaction in glycolysis Hemoglobin functional at 4 structure contained in red blood cells which efficiently carries oxygen from the lings to the tissues of the body also helps transport C02 and H ions back to the lungs K Potassium ion channel functional at 4 structure membrane transport protein Collagen functional at 4 structure holds ligaments tissue muscle etc together Proteases enzymes which hydrolyzes the protein Trypsin hydrolyzes proteins at lysine and arginine Gene Mutation Permanent changes in the base sequence of DNA What are 2 ways gene mutations can arise 0 DNA replication errors not corrected by proofreading 0 Environmental Mutagens radiation chemicals virus What are the 2 main classes of gene mutation Base Substitution and Base insertiondeletion Base Substitution 0 Silent Mutation no change in the protein because the amino acid did not change 0 Nonsense Mutation premature stop because the amino acid changed to a STOP amino acid 0 Missense Mutation amino acid substitution 0 Base InsertionDeletion o Frameshift Mutation the reading frame of codons is shifted by one or two nucleotides 0 Amino Acid insertion an extra codon inserted but the same reading frame Sickle Cell Anemia Missense mutation TA to AT 0 Change in amino acid Glu a negatively charged R group to Val a hydrophobic R group so sickle hemoglobin has a changed 3D shape less efficient binding of OZ stacks in RBSs and distorts their shape 0 Sickled RBCs get stuck in capillaries block blood flow cause pain cries destroyed by spleen l anemia 0 Protein StructureFunction Relationship 0 Protein function depends on the pockets and grooves of the molecule s normal 3D structure 0 Anything that alters the normal 3D structure will alter the function 0 Anywhere from slight change to total loss of function 0 Depends on extent of change 0 What can alter the 3D shape of a protein 0 Denaturation of the protein molecule 0 Mutation in the DNA coding for the protein 0 Hydrolysis of Protein 0 Different interactions bondind help stabilize structure 0 Backbone of proteins are covalent which is a peptide backbone Several kinds of noncovalent interactionsbonding are very important in protein structure MAJOR ROLE 0 These forces are H bonding hydrophobic interactions ionicelectrostatic bonds 0 These noncovalent interactions help to maintain overall 3D structure Covalent like Disul de bonds SS bonds MINOR ROLE o NonCovalent interactions help in formingstabilize structure 0 Hydrogen Bonding can be made whenever possible within a given protein structure Hydrophobic interactions form due to nonpolar R groups of amino acid and other nonpolar regions which try to go away from water minimizing interactions with water 0 IonicElectrostatic Bonds interactions which arise between opposite charges 0 4 Main Tvpe of Biomolecules 0 Nucleic Acids 0 Polymers DNA and RNA mRNA tRNA rRNA o Monomer nucleotides Carbohydrates 0 Polymers Polysaccride and Disaccharides o Monomers Monosaccride LipiE 0 Polymers Triglycerides o Monomers Fatty Acids and Glycerol o Fats and Oils Phospholipids Steroids Waxes 0 Proteins o Monomers aminoacids 0 Support Collagen hormone insulin contractile myosin enzyme hexokinase Ca rbohvd rates Monosaccride simplesingle sugar Polysaccride complex carbs 0 Different Monosaccride contain different numbers andor arrangements of the C H O atoms Dehydration Synthesis of Disaccharides O O O Maltose Glucose Glucose Sucrose Glucose Fructose Lactose Glucose Galactose Polysaccharide aka complex CH0 0 00000 Starch glycogen cellulose Humans cannot digest cellulose lack enzyme to hydrolyze Another name of cellulose main component of plants cell walls quotdietary fiber Glycogen animals stores energy Potato starch chain of glucose Cellulose structure for plants We cannot digest hydrogen bonds Carbohydrate function Mono 0 o Disaccharides Glucose fructose mono sucrose lactose maltose di Short term energy storage Macromolecules all glucose polymers 0 o o o Lipids Starch long term energy storage in plants Glycogen long term energy storage in animals Cellulose structural in plant cell walls and is indigestible ber roughage for humans What atoms are present Mostly C H very little 0 Lack of chare and polarity making the molecule hydrophobic NOT water soluble Fatty Acids o Monomer of triglycerides phospholipid molecules 0 With CC single bonds called saturated H are on the same side BAD 0 With CC double bonds called unsaturated bc it contains fewer hydrogens Cis or trans hydrogen are in the opposite side Saturated or trans fat 0 Straight closepacked fatty acids solid at room tempt vascular damage stroke heart attack all hydrogen Unsaturated oil fat 0 O Lipids O Kinks at double bonds of fatty acids that doesn t lead to clogging healthier Loosely packed liquid at room tempt structural categories 2 major categories of lipids TriglyceridesFats and Oils 3 Fatty Acids and l Glycerol and Phospholipidsamphipathichydrophilic head hydrophobic tail 2 Fatty Acids P04 group 1 glycerol Steroid 4 basic fused ring structure example cholesterol Lipid Function 0 O O O Fats and Oils long term energy storage insulation and cushioning Phospholipids membrane structure separate H20 lled cells from H20 environment Steroids hormones membrane structure and uidity in the membrane Waxes protection prevent dehydration Nucleic Acids ATP Adenosine Triphosphate O O O Adenine base and ribose sugar and 3 phosphate groups Immediate energy molecule in all cells Used as a monomer for making RNA end phosphate group comes off Two Kinds of Covalent Bonds Nonpolar partner atoms share electron pairs equally hydrophobic Polar partner atoms share electron pairs unequally hydrophilic Water is Polar Glucose is also Polar Charged particles are also water soluble so they are polar Methane is nonpolar What do all 4 classes have in common Organics contain 1 or more chemical groups dehydration synthesis making hydrolysis breaking Chemical Groups Hydroxyl OH polar Carboxyl COOH acid negatively charged Amino NH2 base positively charged Phosphate OP02393 buffer negatively charged Methyl CH3 nonpolar reduces polarity Where are chemical groups found Hydroxyl sugars CHOS glycerol Estradiol Carboxyl amino acids protein fatty acids Amino amino acids proteins phospholipids head Phosphate nucleic acids ATP phospholipid head Methyl fatty acids lipids Testosterones Differences Chemical Composition 0 Proteins CHON S COOH charged NH2 charged variety of R groups hydrophilic o Carbohydrates lC2HlO lots of OH polar hydrophilic o Lipids CHO Phospholipid N and P mostly hydrocarbon and CH3 nonpolar hydrophilic 0 Nucleic Acids CHONP P04 charged OH polar on backbone various polar on bases hydrophilic What makes them this way Their chemical groups 0 Cells Lecture 912 What is a cell A basic unit of life cell theorya life consists of one or more cells All Properties of Life 0 Presence of DNA ordered structure reproduction growth and development energy processing response to the environment regulation homeostasis What are the 4 basic structural features common in ALL cells Plasma Membrane 0 Outer boundary separates cell from surroundings o Encloses the cell 0 Controls what leaves or enters the cells Cytoplasm o Fills space within the boundary 0 Suspends or supports internal structure and inclusions Genetic center DNA 0 Controls cell structure and function 0 Governs heredity Ribosomes o Serves as site of protein synthesis 0 Expression of genetic info to develop structure function o Prokaryotes Eukaryotes Size 0 110 pm 0 10100 um DNA 0 DNA circular no limiting 0 DNA linear and paired within membrane nucleoid membrane true nucleus Inclusions Few none membrane enclosed Many most enclosed 12 organelles membrane Ribosomes Smaller 0 Larger Cellular Differentiation Normal process by which immature undifferentiated ce develops distinct structures and functions of specialized cells Underlying mechanism differential expression of genes in DNA 0 Genes turned on expressed l genes turned off silenced Results change in proteome of the cell 0 De nes morphology and specialized function Begins with an undifferentiated cell stem cell Undifferentiated Cells I o Differentiated Cells o Immature cells Specialized mature cells 0 Nondescript morphology Small nucleus large cytoplasm Large nucleus small cytoplasm Speci c protein and internal structures to perform function Contract muscles Transport oxygen Red Blood cells Absence of specialized protein and internal structures associated with specialized function Produce insulin pancreas Examples most cells in very early embryo I I I Transmit electric sngnals neurons very small number in each organ OOOO 2 Main Categories of Stem Cells Embrvonic and Somatic Stem cells are the undifferentiated cells that can differentiated into specialized cells Embryonic Stem Cells 0 Source surplus embryos from in vitro fertilization IVF clinics 0 From inner cell mass KM of blastocyst stage embryo 5 days after fertilization before implantation o Pluripotent 0 Not from absorbed fetuses Somatic Stem Cells 0 From fetus adult tissue eg umbilical cord bone marrow o Multipotent to unipotent o Unipotent a cell between myeloid stem cell and erythrocyte RBC 0 Mature RBC has no nucleus Cell Type Potency o Specialize to 0 Examples 0 Zygote fertilized o Totipotent o All type of cells 0 egg including placenta 0 Inner Cell Mass 0 Pluripotent 0 Nearly all cell 0 types no placenta o Hematopoietic o Multipotent 0 Many cell types 0 Bone Cartilage SC Fat 0 Mesenchymal SC 0 Proerythroblast o Unipotent 0 One cell type c RBCErythrocytes What three features de ne Stem Cells Unspecialized Undifferentiated Able to specialize differentiate into different levels of potency plasticity Able to selfrenew produces 1 replacement SC and 1 daughter cell ready to differentiate Induced Pluripotent Stem Cells iPSC Adult differentiated cell eg skin keratinocyte Treated with 4 genes to genetically reprogram the cells Results cell revert to earlier less differentiated state and act like pluripotent SC Research and medical treatment of patient without rejection Extracellular Matrix ECM ECM mostly protein material at outer surface of cells plasma membrane and between cells ECM molecules on outer surface 0 Allows cells to attach to other cells and to ECM 0 Includes receptors for hormones growth factors 0 Provide cell recognition identity to self 0 Are entry points for viral infections ECM materials between cells provide o Scaffolding for tissue architecture collagen and other bers 0 Anchoring for cells ECM act as a signal for stem cells to differentiate Phospholipid PL Main component phosphate group and glycerol Hydrophilic head and Hydrophobic fatty acid tail Bilayer Barrier between watery cytoplasm and cell s watery environment 0 Prevents loss of material from cell and entry of material from outside the cell 0 Hydrophobic tails won t let dissolved hydrophilic material through Plasma Membrane Structure 0 Proteins intracellular junctions transport signal transduction attachment to the cytoskeleton and ECM Enzymatic activity cell to cell recognition receptors for hormones 0 Cholesterol no cholesterol in membrane cell is rigid membrane exibility lateral movement within the cell 0 Carbohydrate Glycoprotein short chain of sugars attached to a protein l Glycocalyx identity tag Plasma Membrane Function Limiting boundary separate cell from its environment Transport material in and out of the cell Identi cation and Recognition of many different molecules ex ABO blood type Communication cells able to communicate with each other Attachment OOOOO Membrane Function 2 Transoort Diffusion movement of atomsionsmolecules down their concentration gradient from high to low concentration until equilibrium is reached no external energy input needed Osmosis the movement of water molecules from high to low concentration through a membrane Concentration Gradient a difference in concentration across space Equilibrium particles are equally distributed in space Types of barriers 0 Fully Permeable everyone can go through 0 SemiSelectively Permeable allows certain molecules to go through 0 lmpermeable doesn t allow anything to pass Solution Solute Solvent eg salt water salt water Solution solute starts as a solid dissolved in a solvent liquid Tonicity the amount of solute in a solution lsotonic one solution solute another solution Hypertonic more solute the cell shrives because too much water is leaving the cell Hypotonic less solute than another solution the cell burst because too much water is coming into the cell 0 Size Polarity Charge 0 Can it cross the phospholipid bilayer 0 Very small particles no charge 0 Yes it can go through the PL tails 0 Very small particles charged 0 NO it cannot go through the PL tails 0 Small particles no charge 0 Yes it can go through the PL tails Large structure no charge 0 Yes it can go through the PL tails Larger structure charged 0 NO it cannot get through the PL tails Polymer charged or uncharged NO much too large to pass though What limits ability to cross the PL Bilayer Size and PolarityCharge 0 Simple Diffusion o Facilitated o ActiveTransport Diffusion 0 Concentration 0 DOWN 0 DOWN 0 UP AGAINST Gradient Cellular energy 0 NO 0 NO 0 YES required Transport Protein 0 NO 0 YES 0 YES required Examples 0 OZ C02 ethanol Ions amino acids steroid H20 nucleotides Endocytosis plasma membrane indents forms pocket around material vesicle sides fuse closed vesicle drops into cytoplasm 0 Example amoeba engul ng a food particle white blood cells engul ng a disease agent 0 INTO the cell and YES cellular energy is needed Exocytosis cellular material to be transported packaged in a vesicle vesicle fuses with plasma membrane vesicles opens up releases cell product 0 Example pancreatic cell releasing digestive enzyme broblast releasing collagen bers into extracellular space 0 OUT of the cell and YES cellular energy is needed Membrane Function 3 Identi cation and Recoonition ID tags on cells CHO chains on the outside of the plasma membrane are responsible for cell recognition Example ABO blood groups 0 All humans have either A B AB O blood type Immune system recognizes foreign blood types because different short CHO chains Al blood speci c sugar chains Bl blood speci c sugar chains O lacks sugar chains 0000 Membrane Function 4 Communication General schemes of intracellular signaling in animals 0 Endocrine Signaling hormones in the blood stream 0 Paracrine Signaling o Autocrine Signaling cancer cells have this 0 Signaling by plasma membrane attached proteins Signal transduction series of molecular changes that converts amplifying a signal received on outside of cell s membrane 0 Across the membrane through the cytoplasm to the target moleculestructure in cell to elicit a response 0 One molecule alters another molecule which then alters a third molecule etc called a domino effect process cannot stop the end product of signal transduction is a new protein 0 Transmit the message to the appropriate parts of the cell 0 A signal molecule is released by a cell in one part of the body received by a target cell elsewhere the receipt of the signal is via binding of signal molecule to a speci c receptor proteins on outside of the target cell membrane Membrane Function 5 Attachment cell can attach to the ECM and other cells Cell attachment via quotjunctionquot junctions has no physical connection with cells except gap junctions Tightjunction Anchoringjunction Gapjunction Tightjunction 0 Looks like the adjacent membranes are sewn together 0 Forms a water tight seal between the two membrane 0 Prevents passage of material between the cells Anchoring junction 0 Cytoskeleton element connect to assist with structure 0 Connect the intermediate laments of the cytoskeletons of adjacent cells desmosomes 0 May also anchor to a cell s intermediate laments to ECM 0 Provide mechanical strength to the tissue by connecting many cells together Gap Junction 0 Forms pores that provide direct connection between the cytoplasm of adjacent cells 0 Allow ow of molecules and ions from one cell to the next 0 Permit communication between adjacent cells that coordinate the tissue s reaction l 2 3 4 5 6 7 8 9 Internal membranes have the same structure as plasma EXCEPT no glycocalyx Eukaryotic Organelles What are organelles Structures within a cell which with characteristic morphology and specialized function What separates one organelle compartment form another and from the surrounding cytoplasm Membrane What are examples of organelles surrounding by 0 One membrane ERSER RER Golgi lysosome 0 Two membranes 2 adjacent phospholipid bilayers nucleus and mitochondria o No membrane ribosomes bers of cytoskeleton What are the speci c advantages of compartmentalization Increased surface area eg inner mitochondrial membrane Increased concentration of reactants used in chemical reactions reactant concentrations control rate of reaction Separation of incompatible reactionsreaction environment 0 Synthesis vs degradation eg RER vs lysosome 0 Reactions that need different environment pH 7 cytoplasm pH 5 lysosome Separation of products based on whether they are for internal use inside a membraneenclosed organelle or free oating in cytoplasm and export collagen of ECM insulin digestive enzyme Organelles Nucleus double membrane nuclear envelope continuous w ER stores DNA to control cell s structurefunction an heredity Nucleolus site of rRNAcoding genes ribosomal subunit assembly of rRNA and ribosomal proteins Chromatin stretched out form of chromosomesDNA active gene expression Nuclear Pores protein and RNA traffic Ribosome contains Large and small subunits empty tRNA leaving the ribosome tRNA in the P site tRNA in the A site Free Ribosome oating ribosomes in the cytoplasm making proteins in the cytoplasm a Translation of proteins used in cytoplasm eg hexokinase and hemoglobin Bound Ribosome ribosomes attached to RER involved with translation of membrane proteins a Proteins to be inserted into the PL bilayers of the membrane b Proteins for export from cell by exocytosis c Proteins for membraneenclosed cellular organelles Smooth endoplasmic reticulum SER single membrane lipid synthesis synthesis of new membrane synthesis of testosterone and estrogen detoxi cation liver cells calcium ion storage esp muscle cells Rough endoplasmic reticulum RER single membrane ribosomes that attach to ER membrane membrane associated proteins proteins for delivery proteins for release our of cells 10Golgi apparatus single membrane nishes sorts packages ships cell production llLysosomes single membrane contain mixture of hydrolytic enzymes ACID HYDROLASES works in acidic conditions have optimum pH in acidic range intracellular digestion cell recycling center unneeded molecules and damaged organelles 12Mitochondria double membrane cellular respiration ATP Synthesis huge surface area thrown into long folds cristae in order to t inside of the smaller outer membrane site of mitochondrial electron transport chain ETC l3Cytoskeleton 3D network of protein bers in the cytoplasm for structural support scaffolding and cell movement a Micro laments thinnest bers can be assembled and reassembled protein globular protein function cell shape and whole cell movement b Intermediate Filament intermediate bers generally not disassembled and reassembled various brous proteins function cell shape reinforcement of cell junction organelle placement actin c Microtubules thickest bers hollow tubes can be disassembled and reassembled protein tubulin globular protein function arrangement of organelles intracellular transport cell motility the separation of chromosomes during mitosis Properties 0 Plasma Cell Membrane 0 Cell Wall 0 Chemical 0 Mostly lipid proteins some 0 Mostly cellulose Composition carbohydrates 0 Thickness 0 Thin 0 Thick o Flexibility 0 Flexible laterally uid 0 Stiff rigid o Permeability o Selectively permeable Porous v permeable Location 0 Outer layer of cell 0 External to PM 0 Function Gatekeeper Structural support 0 Cell type w 0 ALL 0 Plant cells some fungi this structure Metabolism Lecture 1316 Matter and Enerdv Matter anything that takes up space and has mass Energy ability to do work Kinetic Energy energy of motion example heat light anything moving Potential Energy stored energy energy of position arrangement example chemical arrangement physical placement 0 Kinetic Energy 0 Potential Energy o Skier going downhill mechanical o Skier poised at top of hill position 0 H20 owing down slope from dam 0 Battery arrangement o Electrons moving in a wire electrical 0 Chemical bond energy arrangement Random thermal motion of atoms and 0 molecules heat 0 Concentration gradient arrangement 0 H20 above a dam Photon moving light Moleculeion owing down concentration 0 gradient mechanical Moleculeenergy in bonds holding atom together arrangement What rules oovern enerov use The Law of Thermodvnamics lst law the quantity of energy in the universe is constant energy cannot be created or destroyed only converted from one form to another but the total amount of energy in the universe doesn t change 2nOI law the quality of energy in the universe is NOT constant the amount of useful energy declines spontaneously meaning that energy transformations occur but are NOT 100 efficient because some useful energy is lost as heat energy Metabolism Sum total of all the chemical reactions that occur in a cell 0 How ces function and dictate o How ces manage matter and energy 0 Consists of many interconnected metabolic pathways Metabolic Pathways A series of chemical reactions in which product of the 1st reaction is substrate starting material of the 2nOI reaction product of the 2nOI reaction is the substrate of the 3rOI reaction etc Linear Pathway example glycolysis Cyclical Pathway example Krebs cycle Two Parts of Metabolism Anabolism makingsynthesis reactions 0 Synthesis production manufacture o Requires energy consumption 0 Eg dehydration synthesis monomerljpolymer of all biomoecues production of monomers form inorganic molecules photosynthesis Catabolism breaking down reactions 0 Breakdown degradation 0 Releases energy making energy available for the cell 0 Eg hydrolysis poymermonomer of all biomoecues nonwater mediated breakdown of an organic monomerjinorganic parts C6H1206 l C02 and H20 glucose catabolism Chemical Reaction Chemical reaction change in bonding relationship betweenamong atoms without any loss of starting atoms conservation of mass It s the rearrangement of atoms basic unit of matter Most chemical reactions go in either direction The direction is usually determined by relative concentration of reactant vs product Heating can provide needed kinetic energy to get reactants moving and colliding In cells ENZYMES are used to avoid damaging high temperature o Exergonic Reactions Catabolic Endergonic Reactions Anabolic Releases energy makes energy available to cells Consumes energy requires energy input by cell Energy in reaction is higher than energy in products which is lower so energy is Requires needs energy for reaction to take place released out of the system 0 Starting reactant is low 0 Energy of reactants is greater than the 0 Energy of reactants is less than the energy energy of the products of the product 0 Energy releasedout 0 Energy requiredin Order to random 0 Random to order 0 Degradation or breaking down of complex 0 Synthesis building a more complex structure to smaller structure structure from less complex material Energy Hull Diagram EHD Endergonic Reactions MES Max End Start think you enter the room as a mess Exergonic Reactions MSE Max Start End think you exit the room messy AG difference in potential energy levels of reactants and products EA energy of activation kinetic energy input needed for reactants to reach transition state start to max 0 Enzymes reduces the energy of activation EA Transition State the max energy level in the chemical reaction reactant bonds are breaking product bonds are forming when reached the chemical reaction nishes and products are release start to end Coupled Reactions or processes Two reactions are coupled if something from the 1st reaction is essential needed from the 2ncl reaction The 39something can be a molecule in 2 sequential reactions the product of the 1st reaction is the reactant for the next reaction The 39something can be energy the energy needed to run an endergonic reaction These 2 reactions are said to be energetically coupled Exergonic and endergonic reactions are connected quotcoupledquot in cells 0 Energy released from exergonic reactions is used to drive endergonic reactions So cell uses two sets of coupled reactions 0 One set uses energy from food to make to restore supplies of ATP 0 Another set uses ATP breakdown to fuel cellular work ATP is coupling molecule in the middle appears in both sets of coupled reaction 0 First being made 0 Then being consumed 0 Enzyme Biological Catalysts Help the reaction to take place but are not used up in the chemical reaction Substrate Reactants Enzyme Products Enzyme Speed up the rate of chemical reactions speeds up reaction 106 fold by lowering the EA no change in AG Makes the reaction easier because the transition state is easier to reach But does NOT provide energy Why are enzymes essential to living systems 0 Cells utilize many kinds of BIOCHEMICAL reactions like 0 Anabolic reactions endergonic or Catabolic reactions exergonic At body temperature of 984 F37 C chemical reactions wouldn t be able to take place at a sufficient rate wo an enzyme APOENZYME protein part of enzyme COENZYME organicCOFACTOR inorganic whole complete ENZYME Enzyme 3D conformation enables enzyme to have many small pockets and grooves active site and allosteric site Active Sites of Enzvmes 1 Is a 3D region formed by groups that come from different parts of amino acids sequence Is a relatively small part of the total volume of an enzyme Directly participate in the making or breaking of bonds Is structurally complementary to the substrate 0 Shapelock and key concept of enzyme substrate binding 0 Chemical composition charge polarity o Substrates bind by a multiple weak attraction with R groups of enzymes Anything any agent which causes the change in shape of active site will affect the enzyme activity or function 0 Inhibition of enzyme 0 Denaturation of enzyme 0 Permanent alteration in gene level Is the site where a competitive inhibitor binds if present The Catalytic cycle of an enzyme Enzyme available with empty active site 2Substrate binds to enzyme with induced t 3 a Keeps substrate from diffusing away b Holds substrate in close proximity and current orientation to help bond formation and breaking c Strains stresses the substrate bond making them easier to break Substrate is converted to product a Water is added 4 Products are released a Chemical reaction occurs b Induced t is released c Products are released How does the catalytic cycle accelerate the rate of a chemical reaction Reduces the EA of reaction through induced t 0 Keeps substrates from diffusing away 0 Holds substrate close to each other and o Incorrect orientation in active site 0 Strains reactant bonds makes reaction easier NO effect on AG free energy difference between energy of reactants and products Control of enzyme activity Enzymes are proteinsif disrupt 3D shape changelose enzyme activity How can that happen 0 Heat over 45 C Extremes of pH Extremes of salt Foaming Mutation Would these conditions ever be used by cells to control enzyme activity 0 Cells maintain constant internal conditions homeostasis 0 High fever from illness would cause mild reversible denaturation but not used as a wat to control enzymes 0 Mutations may occur through error but again not a control mechanism Control of enzvme activitv bv cells Rate of synthesis and its rate of degradation controlled Start or stop making the enzyme certain genes can be quotturned onquot or quotturned offquot eg lac operon in Ecoi the presence of lactose Accessibility of substrate the transfer of substrates from one compartment of a cell to another can serve as a control point controlling the entry of substrates can regulate enzyme activity Isolate active enzyme in a separate compartment enzymes are often con ned to speci c locations in the cell and work only there Activation some enzymes are made in an immature inactive form and get activated wherewhen appropriate Enzvme Inhibitors Competitive inhibitor inhibitor can bind on the active site of enzyme complex as it resembles substrate 0 Irreversible inhibitor covalently bound to the active site 0 Reversible inhibitor loosely bound can diffuse off Noncompetitive Allosteric inhibitors inhibitor and substrate can bind simultaneously to an enzyme molecule at different binding sites other than the active site Competitive Inhibitor blocks active site Noncompetitive or Allosteric inhibitor changes shape of active site 0 Binding is reversible activity is restored if inhibitor comes off 0 Binds and changes 3D shape of enzyme indirectly closing off active site Feedback inhibition example of noncompetitive inhibitor NOT a type 0 Pathway on enzyme present and active all substrate present 0 Pathway off enzyme quotaquot present but inactive thus no substrate BCDE present 0 Speci c example of feedback inhibition pathway that converts threonineisoleucine o Isoleucine is a different amino acid Two types of carrier molecules involved in glucose catabolism e39H carrying coenzyme o NADNADH and FADFADH2 0 Hold energy temporarily later 39cashed in39 for ATP Energy carrier molecule 0 ADPATP 0 ATP immediate energy molecule used in all cells e39H carrvinq coenzvmes NAD and FAD Picks up HIGH ENERGY electrons and accompany hydrogen ions H aka protons from the substrate in the active site of the enzyme Carrying them to another location in the cell where they can be used Empty out their 39cargo in that location Come back in empty states to assist the same reaction again What do NADH and FADH7 do with their e39H Hold the e39H for only a short time Shuttle e39Hfrom one place to another WITHIN the cell 0 From where they are picked up glucose 0 To where they can be used mitochondria ETC Once cargo is delivered empty oxidized carriers go back for more shuttle service What can delivered e39H be used for Produce ATP Reduction and Oxidation Type of chemical reaction that transfers electrons from 1 structure to another The 2 reactions occur together 0 When one structure gives up electrons 0 Another structure receives itthem 0 So electrons isare transferred Together called Redox reaction 0 Oxidation is the loss of electron the structure that loses electrons becomes oxidized 0 Reduction is the gaining of electrons lthe structure that gains electrons is reduced 0 This is counterintuitive Le a reduction is gain 0 When the CHZOn is oxidized loses hydrogens NAD and FAD pick them up reduced Limited ATPADP supplies in the cell Can t be passed from cell to cell Very hard for cell to make from scratch ATP ADPPi need to be cycled constantly within cell If a cell can t cyce ADP back to ATP it will die Reactions of Glucose Catabolism l CsleOs 6 02 l 6 C02 6 H20 3638 ATP 40 ATP 60 heat C6H1206 2NAD 2ADP 2P 2 Pyruvate 2 NADH 2 ATP Oxygen absent Fermentation Oxygen Present Cellular Respiration ATP Svnthesis ATP synthesis is an endergonic process Energy transformations are 40 efficient 60 energy is lost as heat What is the main source of energy to produce ATP 0 KE of electrons removed from organic molecules during catabolism o Flowing down mitochondrial ETC 0 Producing protonsH gradient across inner mitochondrial membrane 0 Potential energy in this gradient is used to synthesize ATP by chemiosmosis How does a cell make ATP from ADPPi Direct Phosphorylation aka Substrate Level Phosphorylation o Requires an enzyme 0 Requires a phosphate group donor which has high energy phosphate group transfer potential compared to ATP 0 Energetically coupled w exergonic reactions in the glucose catabolism pathway Glycolysis cytoplasm and Krebs cycle Mitochondria 0 Source of 10 of a ce s ATP Chemiosmosis 0 Source of 90 of a ce s ATP 0 Energy source H proton gradient from ETC drives ATP synthesis by chemiosmosis o Occurs in mitochondria in eukaryotes o Occurs in cytoplasm in prokaryotes Three cateoories of cellular work o CHEMICAL Category 0 MECHANICAL Category 0 TRANSPORT Category Endergonic Rxns eg Muscle contraction Active transport across DNA synthesis Motor proteins inside of membranes RNA synthesis cels Protein synthesis Lipid synthesis What is an e39 transoort chain ETC A series of e39 transport protein inserted in the PL bilayer of the inner mitochondrial membrane Each protein can accept 2e39 Each protein then passes these e39 to the next protein in the series The flow of e39 down the chain provides kinetic energy There must be an e39 donor at the start and a nal e39 acceptor at the end of the chain ETC energy from e39 ow along ETC used to pump actively transport H across membrane H gradient across membrane Chemiosmosis ATP Synthesis from ADPPi using energy from flow of H ions back down gradient facilitated diffusion through channel protein ATP Synthesase complex Glucose Catabolism Glycolysis Prep Stage Krebs cycle ETC Chemiosmosis Glycolysis o 1 Glucose l 2 Pyruvates 2 ADP l 2ATP 2 NAD2 NADH H ATP is made by substrate level phosphorylation Glucose is broken down by enzymes lst enzyme used in glycolysis to breakdown glucose is Hexokinase Occurs in the cytoplasm Breaks down glucose into 2 3C molecules Pyruvates 9 step metabolic pathway Anaerobic doesn t consume 02 or indirectly dependent on O2 Transition Stage Prep Stage 0 Pyruvate is converted to Acetyl CoA which enters the Mitochondrial Matrix 0 C02 molecule is released 0 End Products of Prep Stage 2 Acetyl CoA and 2 NADHH 0 Enzyme Responsible pyruvate Dehydrogenase o Aerobic Krebs Cycle 0 6 NAD 6 NADH 6 H 2 ADP l 2 ATP 2 FAD l 2 FADH2 0000000 0 ATP made by substrate level phosphorylation occurs in mitochondrial matrix 0 End Product of Krebs Cycle 2 FADH2 2 ATP 6 NADH2 4 C02 0 1 FADH2 2 ATP 0 1 NADH 3 ATP 0 Aerobic o 4 remaining carbons from pyruvates as C02 0 A cyclical metabolic pathway ETC 0 NADH and FADH2 shuttles through until it reaches 02 which is the nal electron acceptor H actively transport outer mitochondrial membrane 0 ETC embedded in inner mitochondria membrane Series of electron acceptors e39 source NADH and FADH2 and a nal e39 acceptor Oxygen Chemiosmosis o H has stored potential energy which drives H through channel in ATP Synthase facilitated diffusion which during this stage actively catalytic sites add P04 groups to ADP to make ATP 0 A large complex motor protein 0 Embedded in inner mitochondria membrane at the end of each ETC 0 Produces ATP through a series of energy transformations What if there is no Oxvoen What happens to the ETC Electron ow stops without nal electron acceptor What happens to the ATP Synthase Stops because H ion ow stops if there is no gradient across membrane What happens to the Krebs cycle Stops as the cell s entire supply of e39H carriers are lled because they cannot get rid of cargo since the ETC has stopped What has to transition reaction prep step Stops because it depends on a lower concentration of pyruvate in mitochondria matrix but if the pyruvate is not being used by the Krebs cycle the gradient is lost What happens to glycolysis Stops if there is no empty NAD unless the cell can switch to fermentation a process that regenerates a small amount of NAD to keep glycolysis going What happens to the cell Dies in 510 minutes because of lack of suf cient ATP Genetics Lecture 1720 Homologous Chromosome Pairs Each bodysomatic cell contains 2 copies of each human chromosomeDNA molecule Are present in all stages of cell cycle G1 GO S G2 MP M A T C Can be in chromatin fully extended or chromosomes fully compacted form depending on the stage of cell cycle Cen be replicated or unreplicated These 2 copies are a pair Homologous because they have 0 Same length 0 Same centromere position 0 Same sequence of gen but Not necessarily same variants alleles for each gene because each member of the pair is from a different parent o HCP Homologous Chromosome Pair 0 SC Sister Chromatid Same length same centromere position same sequence of genes bc they are the same chromosome 0 Each one side one 12 of a replicated chromosome Each contains 1 of 2 daughter DNA molecules made S phase NOT the same sequence of alleles because 1 mat and 1 pat o Are identical in both gene and allele sequence Never attached to centromere 0 Always held together by the centromere Appear in metaphase thus are replicated Separated at anaphase they are independent chromosomes o Diploid o Haploid Number of chromosomes in a body cell Gametes required to restore 23 chromosome Characteristic of a species 0 One half the diploid number Always even number bc chromosomes 0 Only 1 member of each type pair present occur in pairs m or p 0 Both HC members of each pair present in c When 2 haploid cells fuse the diploid state the cell is restored Abbreviation 2n Abbreviation n 0 Asexual Reproduction Sexual Reproduction 1 parent cell 2 parents multicellular organism ls mitotic division Parent no longer exists after reproduction Requires Meiotic Division each parent produces a gamete and Fertilization gamete fusion Minimal genetic variation Parents still exist after reproduction Mutation Maximal genetic variation mutation and mixing of DNA from parents Gene 0 Allele Speci c location on the chromosome of 1 DNA molecule 0 The actual base sequence present at this location in the DNA Designated by cytogenetic location on short or long are of chromosome and base pair 0 Different alleles differ from one another by at least one bp 0 New alleles arise from existing alleles by mutation Where info is stored to produce a protein with speci c function Eg HEXA gene chromosome 15q24l 0 Some slightly different sequences may code for a functional enzyme Role of Meiosis to reduce chromosome in cells from 2n diploid l n haploid Startino cell for Meiosis Only selected cells go through meiosis These cells are diploid cells in the reproductive organs of an individual In males primary spermatocytes located in the testes In females primary oocytes located in the ovaries Gives form to haploid gametes Gametes once formed DO NOT divide again Egg is among the largest cells in an organism immobile cell Spermatozoa is often the smallest cell very active cell high mobility o Mitotic Cell Cycle 0 Meiotic Cell Cycle Produces 2 diploid cells Produces 4 haploid gametes egg or sperm from 1 diploid parent cell Same amount of DNA as parent cell same 2 0 copies of each gene Half the amount of DNA as parent cell 1 copy of each gene bc 1 chromosome of each type o Daughter cells go through cell cycle again Gametes don t divide will fuse w gamete or go in GO from other parent or die 0 The 2 daughter cells are EXACTLY the same 0 2 meiosis divisions 2 daughter cells at as the parent cells Meiosis 1 has 1 chromosome pair and forming 4 haploid cells Meiosis 1 Separation of the homologous chromosome ie maternal copy goes to one daughter cell paternal copy goes to the other daughter cell Sister chromatids still together but daughter cells are haploid m and p are NOT in the same cell anymore Unique kind of division quotreduction divisionquot 2 haploid daughter cells made from one diploid parent cell Both cells from meiosis 1 go on to meiosis 2 Gametes once formed do not divide any further Meiosis 2 Separation of sister chromatids ie each daughter cell gets just one copy of either maternal or paternal chromosome of each type Mitosis like division of haploid cells from meiosis 1 4 cells made gametes Three Kev Events in Meiosis 1 Prophase 1 o Tetrads form homologous chromosomes mat and pat comes together 0 Tetrad held together by protein glue holds HCP o Spindle bers attach to both sides of whole tetrad o Tetrad formation spindle bers are only attached to 1 chromosome end 0 Spindle bers made from microtubules Metaphase 1 o Tetrads HC s are lined up at equator not individual chromosomes as in mitosis o All the tetrads will line at the equator Anaphase 1 0 NO centromere division 0 Instead protein glue holding tetrad together dissolves melted 0 Mat and pat chromosome are separate 0 Result 2 haploid cells a cell with only 1 member mat OR pat of each HC pair even if still replicated is HAPLOID Origin of genetic Variation Gene mutation very rare In the germ line ie in gametes or in cells that become gametes Chromosomal aberration very rare in the germ line Sexual Reproduction every meiosis main source of genetic variation 0 Meiosis crossing over in prophase 1 and independent assortment of chromosomes in metaphase 1 o Fertilization random fusion of gametes Crossino over aka oenetic recombination o Prophase 1 of meiosis 0 Even exchange of genetic info with in each tetrad 0 Between maternal and paternal chromatids Occurs in at least one place one each human chromosome more places on long chromosomes 0 Genetic DNA recombination DNA from 2 different sources recombined into 1 DNA molecule 0 Chiasma point at which nonsister chromatids cross over 0 Assuming only 1 crossover per tetrad crossing over yield 4 genetically distinct gametes for that pair of chromosomes 0 But crossing over occurs in all tetrads and at multiple sites along the chromosome 0 So crossing over by itself yields a HUGE almost in nite variety of potential gametes over an individual s life 0 RESULT 4 different possible combos of mat and pat genetic info at metaphase 2 and in gametes 0 Another source of genetic variation from Meiosis Independent Assortment of HC s Tetrads of different types of chromosomes line up independently of each other at metaphase 1 position of mat vs pat chromosome random 0 Therefore which pole the mat and pat chromosome moves to is random for each type of chromosome 0 In a cell with 2n4 25ets of homologous chromosomes 0 Half the time the 2 mat chromosomes will move to 1 pole and the 2 pat chromosomes will move to the other pole o The other half 1 mat and 1 pat will move to each pole 0 Genetic Variation from sexual reproduction in humans 0 Shuf ing of alleles variants in genes into new combination in off springs o Crossing over minimal of 82 x 106 genetically combos 0 Independent assortment 82 x 106 genetically different combos 0 Random Fusion of genetically distinct gametes Fertilization 5x1027 possible genetically distinct offspring Errors in Meiosis and Chromosomal Aberrations Chromosomal aberration multigenetic change in the number andor structure of chromosomes in a cell Nondisjunction error in chromosomechromatid separation in meiosis 1 or 2 Trisomy autosomal chromosomes 0 results of fusion of gametes with 24 chromosomes or 23 chromosomes 0 most are lethal embryofetus dies in utero miscarriage and a few are viable o eg trisomy 21 Down Syndrome XXY Kilnefelter Syndrome XO Turner Syndrome Other Chromosomal Aberrations Mistakes in Meiosis unequal crossing over Other inappropriate break and swap events 0 Chromosomal inversion 0 Chromosomal deletion 0 Chromosomal duplication 0 Chromosomal translocation Stages of Meiosis 0 Pro 0 The DNA coils tightly and individual chromosomes become visible under the light pha microscope Homologous chromosomes become closely associated in synapsis and se1 they exchange by crossing over 0 Met 0 The nuclear membrane has disappeared and the microtubules form spindle bers aph attach to only 1 side of each centromere and the 2 homologous chromosomes ase attach to microtubules orienting opposite poles Each pair lines up on the 1 metaphase plate 0 Ana 0 The microtubules of the spindle ber shorten and pull the chromosomes to the pha poles taking both sister chromatids with them Each pole ends up with a complete se haploid set of chromosomes consisting of 1 number of the homologous pair 1 o Telo o The nuclear membrane reforms around the daughter nuclei Each daughter nucleus pha contains 2 sister chromatids for each chromosome attached to a common se centromere 1 0 Pro 0 The nuclear envelope breaks down and a new spindle forms pha se 2 0 Met Spindle bers bind to both sides of the centromere aph ase 2 0 Ana 0 The spindle bers contract and the sister chromatids move toward opposite poles pha se 2 o Telo o The nuclear envelope reforms around the sets of daughter chromosomesgt results pha in 4 daughter cells se 2 Tav Sachs Disease Chromosome involved 15 Gene involved HEXA Number of chromosome 15 copies in your cells Two Number of copies of HEXA gene in each of your cells Four Versions of HEXA gene alleles O 0 Normal allele H Mutated allele h Possible allele combos genotypes gene copies present 0 O 0 HH Homozygous normal Hh heterozygous hh homozygous mutated Possible traits phenotypes what shows up 0 Healthy HH and Hh o Affected with Tay Sachs disease hh Gregor Mendel Austrian monk 18221884 0 Contemporary of Darwin 180982 Used the garden peas Pi Sum Satiuum o Selfpollinating ower structure closed ower both m and p parts 0 True breeding strains available homozygous 0 Carefully selected characters each with only 2 possible traits o 7 traits ower colous pod color height etc 0 Very high sample numbers nearly 300000 individual plants analyzed 0 Performed cross pollination reproductive event experiments Developed 2 laws to explain inheritance of genetic characteristics Published in 1866 Not widely read until rediscovered 1900 True Breeding plants consistently produce offspring with same traits as parent for a given character through the generation homozygous SelfPollinating pollen from a plant fertilizes eggs from same plant 1 Selfpollination pollen from the male anther of a plant falls on the female stigma of that same plant 2 Fertilization sperm from the pollen fertilize the plant s eggs which lies inside the ovary These eggs will develop into seeds in the ovary which represent a new plant generation Each seed is fertilized separately 3 Germination each seed can be planted and grown into a separate plant 4 Development seedling develop into mature seed plants Mendel s crosses First step 0 Intentional cross pollination of 2 parents P both true breeding for a given trait 0 Allow parents to set seed 0 Collect seeds 0 Germinate seeds and allow to grow to maturity and to ower 0 Observe all offspring F1 for trait Second step 0 Allow F1 offspring from above cross to selfpollinate 0 Observe F2 generation First Mendel followed the inheritance pattern of ONE character with 2 trait Shown here using ower color as example parental plants were true breeding for their respective ower colors Mendel s Laws of Inheritance Law of gene segregation o In each diploid individual there are 2 copies of every gene 1 from each parent that reside on homologous chromosomes 0 These gene copies are separated into separate gametes during gamete formation meiosis Law of independent assortment o 2 different UNLINKED on different HCP genes assort independently of each other during gamete formation meiosis 0 That means that a particular gamete may end up containing the maternal copy of gene A but the paternal copy of gene B Genes inherited in tvpical Mendelian Pattern Have 2 alleles 1 dominant 1 recessive Are autosomal not on X or Y Are therefore gender independent 1 copy from each parent to each offspring TWO or MORE GENES INHEIRTED IN THIS WAY Are unlinked ie on different chromosome Ex one gene is chromosome 1 and another is chromosome 4 Examples of Mendelian Inheritance in Humans TaySachs disease PKU Phenylketonuria Cystic Fibrosis Sickle Cell Anemia Huntington s Disease Achondroplasia Variation on Mendelian Inheritance Pattern and Non Mendelian Inheritance Pattern Gene with multiple alleles Genes whose alleles differ in level of dominance o Incomplete dominance o Codominance Polygenic inheritance Sexlinked inheritance Maternal inheritance Multiple Alleles 1 Gene with more than 2 alleles Example ABO blood type One character One gene chromosome 19 Three alleles o IAIA and W are Blood Type A IBIBand IBare Blood Type B IAIBare Blood Type AB ii are Blood Type O 4 possible phenotypes ABABO Incomplete Dominance neither allele appears fullv dominant over the other 2 allelele recessive allele r and 1 quotlow dosequot dominant allele R 3 genotypes and 3 phenotypes 2 extreme phenotypes and l immediate phenotype Low does quotdominant allele codes for small amount of product Example Hypercholesterolemia 0 HH individuals low blood cholesterol levels healthy 0 Hh individuals tend to have high cholesterol with diet may need cholesterol lowering drugs 0 hh individuals dangerously high cholesterol levels prone to stroke heart attack at a young age even with drugs Example Flower Color 0 RR red rr white Rr pink Codominance Two alleles for a given gene are codominant if both are fully expressed additive when present together Example Individuals with AB blood type IAIB have both CHO A and CHO B present on the RBC surfaces Polygenic Inheritance 1 character controlled by 3 or more distinct genes Leads to a continuum of traits rather than just extremes Example eye color height human skin color o of o of o Genotype examples Phenotype dominant recessive skin color alleles alleles 6 o 0 AABBCC 0 Very dark 5 o l o AaBBCC AABch AABBCc 0 Dark 0 4 o 2 o AaBbCC AABbCC etc 0 Medium dark 0 3 o 3 AaBch AABbcc etc 0 Medium 0 2 o 4 Aabch aabbCC etc 0 Medium light 0 l o 5 aaBbcc aabch 0 Light 0 0 o 6 aabbcc 0 Very light O Sickle Cell Anemia Pleiotropy 1 gene controls several apparently unrelated character Symptoms many seemingly unrelated Sickle cell hemoglobin sickleshaped RBCs that get stuck in small capillaries of organs debilitating pain crisis organ degradation extreme anemia bc RBC destruction by spleen Underlying causes symptoms actually all related 0 Amino acid substitution from missense mutation sickle cell hemoglobin stacks ad deform RBCs cells block blood flow in capillaries oxygen deprivation in organs pain and organ 0 O O O O O O O O degradation abnormal shape of RBC targets them for destruction by spleen Symptoms of sickle cell anemia are almost fully recessive 2 alleles that differ by 1 bp for the globin protein affect in sickle cell anemia HbA codes for hemoglobin A the usual functional form of hemoglobin HbS codes for a slightly different hemoglobin 1 amino acid difference that is also fairly functional What are the possible Genotypes HbAHbA individual is healthy HbAHbS heterozygote individuals are healthy but may begin to show symptoms under stress HbSHbS individual shows all symptoms Sexlinked genes and character Genes located on X or Y chromosome but NOT both Chromosome combo determines gender XX or XY Xlinked Phenotype appears more frequently in males male expresses the single allele he receives cannot be heterozygoushomozygous called hemizygous male always receive X from mom and Y from dad Examples colorblindness and DMD Ylinked Only present in males always passed from father to son allow us to follow the male lineage going back 10000 yrs Mitochondrial Inheritance nonnuclear genes carried in DNA of mitochondria only inherited from mother allows us to follow the female lineage going back 100010000 years Ecology and Evolution Lecture 2124 0 Ecology 1 Individual one living creature the study of interactions of organisms with each other and with their environments Habitat speci c environment an organism lives in Ecosystem includes both biotic and abiotic components Ecolooical Levels of Biolooical Organization Population all the individuals of ONE Species in a de ned area Community sum of ALL populations species in a de ned area Ecosystem biological community PLUS abiotic environment high level of interaction between biotic living and abiotic components of ecosystem in a large geographic region down to tree stump Biome ecological association extending over a large geographic area which supports a speci c array of species adapted to the environment Biosphere sum of all ecosystemsbiomes on earth Varietv of Biomes on Earth Aquatic Biomes freshwater Terrestrial Biomes tropical rainforest savanna dessert chaparral temperate grassland temperate forest coniferous forest Taiga tundra polar ice caps What is a soecies A species is both singular and plural form A group of individuals that can be interbreed to produce viable and fertile offspring and that are reproductively isolated May consist of one or more geographically separate population Population Ecology Population size number of individuals Population Growth Rate how fast the population size increasesdecreasessteady state 3 key factors that in uence size growth rate exponential growth rate population limiting factors carrying capacity Variation in environment Over space longitude latitude altitude proximities to bodies of water Variation over time shortmedium term succession geological time frame tectonic plate movement Annual Growth Rate r of pooulation b d Annual growth of a population r r N o r annual growth rate of population b of births and immigrants d of deaths and emigrants N size of population at start of year Actual value of r balance between 2 opposing factors maximal rate of growth and population limiting factors What is maximal growth rate rmax Exponential growth rate exponential growth gives a curve population increases by a multiplying factor Actual growth under ideal conditions ample space ample resources no hindrances Generally very high greater than need to replace parents maintain population size Different for each species determined by age of sexual maturity of reproductive cycleyear of young producedcycle Pooulation Limitino Factors PLFs Environmental factors that limit population growth by decreasing birth rate increase in death rate Abiotic Factors 0 Seasonal changes in foliage temperature darklight cycles etc grazing reduced for deer in winter light insuf cient for photosynthesis 0 Hurricanes ooding Katrina 2005 1500 death and Sandy2012 mass destruction 0 Tsunamis JapanMarch 2011 o Earthquakes Haiti January 2010 and Nepal2015 o Wild res o Manmade disaster Bp Oil Spill and war Biotic Factors Community interactions 0 Competition for Resources intraspecies competition with in a species and interspecies competition between species 0 Predation Parasite Disease When population limiting factors affect has based on their genetic traits natural selection Selective factors affect individuals changing by natural selection Biolooical Abundance and Diversitv 0 Diversity number of different species the biome can support 0 Abundance number of individuals of each species the biome can support 0 Where is diversity and abundance greater Rainforest and desert What is carrvino capacitv Number of individuals of one species that an environment can support over the long terms of resources and absorbing water 0 Separate CC for each species in each environment 0 nterreated with CC for other species bc other species are a part of the environment 0 Limitation of resources in environment major source of PLFs o PLFs keep populations in check results in an Sshaped curve bc and PLF decrease birth rate and increase death rate so that b d population size constant 0 So actual population growth rate results from interplay between PLFs and rmax What happens if a pooulation exceeds its Carrvino Capacitv Overharvesting of food beyond capacity to regrow temporary reduction of carrying capacity Environment can no longer support as many individuals Technoloov and Biotechnoloov Technology application of new scienti c info to produce a product or process of bene t to humans Biotechnology subset of technology use of a biological system to produce a productprocess of bene t to humans Example of technoloovbiotechnoloov that counter PLFs and increase Carrvino Capacitv Medical and Public Health 0 Decrease death rate eye glasses antibiotics vaccines surgeries golden rice municipal water systems 0 Increase birth rate improved nutrition fertility treatment in vitro fertilization NonMedical o Decrease death rate seatbets weather forecasting and communication technology improved shelters Agricultural 0 Increase CC food suppyincreased quantityincrease yield and decrease loss and less costly and improved distribution with transportation techniques What is the Earth s current CC for humans Ecological Footprint an area of land by individualnationglobally to produce all needed resources and absorb all waste 0 Average US footprint 94 ghaperson Ecological capacity area of productive land in which resources are cased for each nationglobally 0 Global ecological capacity 21 gha 5 acresperson 0 US ecological capacity 5 ghaperson Relationship between footprint to earth s carrying capacity for humans 0 Global human footprint must be s ecological capacity for our population to remain below or at CC The larger the individual footprint 0 The smaller the of individuals that can be sustained the lower the carrying capacity for humans the more likely we 39overshoot CC if the population continues to increase the more likely we face a 39crash Other evidence for exceeding our CC 0 Overharvest of natural resourcesextinction pollution water shortages global climate change coastal ooding and starvation Biolooical Evolution Definition change in the genetic makeup of a population over time o Occurs at the level of the population because individuals cannot change their genetic make Up 0 Individuals do change during their lifetimes development maturation ongoing physiological acclimation o BUT this is NOT genetic change just differential use of the genes or accumulation of damage 0 An individual s genetic makeup is constant no endpoints not goaloriented not intentional Basic idea of Natural Selection 39preexisting genetic variation in all population augment by each reproductive events Overproduction of offspring Competition for limited resources and escape from predation disease PLFs Unequal reproductive success 0 Some individuals produce offspring more successfully than others 0 Based on genebased phenotypes that make them well suited for existing environment 0 This is what counts for evolution viable fertile offspring Subsequent generation have higher proportions of individuals well suited for environment Population as a whole is better adapted t to the environment Two major level of evolution Microevolution 0 Short time frame 10 generation 0 Level within a speciespopulation o Extent of change small changes Macroevolution 0 Geological time frame 1000 to 106 years 0 Level above species levels formation of new species 0 Extent of change large and clearly visible changes Four sources of genetic variation in all pooulations Genetic variation from sexual reproduction main source of genetic variation augmented at each generation new combo of mat and pat alleles at each reproductive event a Crossing over b Independent assortment c Random fertilization Gene mutation at low ongoing rate a Only source of new alleles To be passed on need to occur in germ line cells Mutations change errors NOT responses to need May be bene cial 39harmful or neutralvalue depends on prevailing conditions in environment Different effect depending on categories of gene mutated Chromosomal aberration a Mutagenic changes in structure of chromosomes eg chromosomal duplication from uneven crossing over lmmigration Emigration of individuals tofrom a population a lmmigration increase variation and Emigration decrease variation What factorsoene based attributes can enhance reproductive success Genes that promote survival to reproductive age 0 Escape from predators 0 Resistance to disease Genes that promote ability to acquire suf cient resources 0 Food water shelter space Genes that promote ability to ndattract a mate Chance NOT gene based Which members of a population will be favored Natural selection those whose genetic makeup allows them to survive to the reproductive age acquire suf cient resources nd and attract a mate have plentiful fertile young be fertile and then pass those genic traits on to their offspring Genetic drift those lucky enough to escape death by chance cannot pass this 39luck on to offspring lick is not heritable o Is taking place when a population evolves only due to this type of random errors 0 The smaller the population the less genetic variation it has 0 Small populations more vulnerable to effects of genetic drift 0 In this very small population alleles can be lost from one generation to the next by occurrence of ransom chance events 0 What is needed for natural selection Unequal reproductive success 0 PreExisting and ongoing phenotypic variation based on genetic variation from random mutation minor random genetic variation from sexual reproduction major PLUS 0 Overproduction of offspring rmax more offspring produced that can survive to reproductive age PLUD Limited resources competition predation disease etc Dpopulation limiting factors counteracting rmax 0 LEAD TO Unequal Survival l some individuals survive and others do not selection is not random it is related to genetic traits that make the individual more likely to survive long enough to reproduce and thereby contribute genetically to the next generation LEADS TO UNEQUAL REPRODUCTIVE SUCCESS URS o What is outcome of URS Unequal Reproductive Success those individuals best matched to the environment produce more offspring and the only feature that gives evolutionary value to an individual is its reproductive success because that is the only way traitsalleles can be passed down to future generation 0 LEADS TO 0 Unequal transmission of alleleslj only the alleles carried by individuals that do reproduce are transmitted RESULTS IN 0 Change in allele frequency in gene pool causes level of adaptation of the population to increase 0 REPRESENTS Evolution microevolution genetic change in a speciespopulation over generational time because frequency of allele in gene pool shifts from generation to generation Natural Selection URS of different individuals Individuals whose gene based phenotype is better suited to the existing environment produce more viable and fertile off springs than less well suited individuals Thus in the generationhigher proportion of individuals with alleles from parents that had higher reproductive success and lower proportion of individuals whose alleles less successful parents This produces a change in allele frequency Evolution BY Natural Selection Result of natural selection population becomes better adapted to the existing environment Evolution adaptation is the OUTCOME of natural selection Individuals do NOT adapt in order to survive o lmplies intent implies that an individual can evolve which it cannot an individual survives bc its phenotype happens to be more suited to the existing environment Speciespopulations do not adapt in order to survive o lmplies intent purpose to evolution speciespopulation survive bc they happen to be well suited to the existing environment Three patterns of natural selection stabilizing directional disruptive Stabilizing Natural Selection selected highest point of curve 0 Ex Giraffe long neck but not too long so they can protect themselves 0 Normal human birth weight range of 55 to 10 pounds baby is too small it s likely to die and 0 Both of the extreme phenotype will be select against so the middle phenotype will be if the baby is too large both mom and baby may die so Csection is introduced l example of how medical technology has reduced the effect of natural selection on humans Directional Natural Selection 0 Happens in one speci c direction can be shifted to only one extreme phenotype that is selected 0 Selection against one end of the range or the other can reverse oWhen the complete opposite phenotype gets selected for o What happens in antibiotic or pesticides resistance 0 Example San people in Africa vs Chucchi in Siberia Disruptive Natural Selection 0 When the same species develop 2 different phenotypes adapted for eg eating different food 0 Selection against most common phenotype Evolution of Skin Color Evolution of dark pigmentations in high UV radiation in equator regions Evolution of depigmentation under low UV radiation Hypothesis 0 Lowered death rate from skin burn and increase incidence of cancer 0 Enhanced survival in forest environments 0 Protection of folate metabolism which gives reproductive advantage Folate de ciency interfere with normal development and is related to birth defects thus folate being required for reproductive success sun light harms folate from diet Melanin protects folate destruction Vitamin D synthesis active when sunlight occurs and de ciency is called rickets and osteomalauia Folate is needed for healthy pregnancy Folate is destroyed in the presence of too much sunlight WW Develooment of Pesticide resistance Preexisting genetic variation in population Selective pressure pesticide kills all individuals sensitive to pesticide Survivors with resistant aee reproduce producing a population of resistant insects
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