Download - 5 Genetics
Chapter 5: Genetics and Cellular Function
• Nucleus and nucleic acids• Protein synthesis and secretion• DNA replication and the cell
cycle• Chromosomes and heredity
Nuclear Structure
• Most cells have single nucleus• Enucleate - no nucleus (mature RBC’s) • Multinucleate - 2 - 50 nuclei (skeletal muscle)• Nuclear envelope - surrounds nucleus, has two
unit membranes • Nuclear pores - perforate nuclear envelope• Nucleoplasm - material within nucleus• Chromatin - DNA and associated proteins• Nucleoli-dark staining, produce ribosome
subunits
Nucleus TEM
Nuclear Envelope, SEM
• Nuclear pores– formed by a ring
shaped complex of proteins
– regulates traffic through envelope
– holds nuclear envelope together
Chromatin
• DNA and associated proteins, looks like granular thread
• Nucleosomes - cluster of eight proteins, histones, serve as spools to protect and organize DNA
• Supercoils - preparation for cell division
Chromatin Structure
Nucleotide Structure
• Nucleic acids are polymers of nucleotides
• Nucleotides consist of– sugar
• RNA - ribose• DNA - deoxyribose
– phosphate group– nitrogenous base
• next slide
Nitrogenous Bases
• Purines - double carbon-nitrogen ring
• Pyrimidines - single carbon-nitrogen ring– uracil - RNA only– thymine - DNA only
Complementary Base Pairing
• Nitrogenous bases form hydrogen bonds
• Base pairs– A-T and C-G
• Law of complementary base pairing– one strand determines
base sequence of other
Sugar-phosphate backbone
Sugar-phosphate backbone
Segment of DNA
DNA Structure: Twisted Ladder
DNA Function
• Serves as code for protein synthesis, cell replication and reproduction
• Gene - sequence of DNA nucleotides that codes for one polypeptide
• Genome - all the genes of one person
RNA Structure and Function
• Only one nucleotide chain• Much smaller
– transfer RNA (tRNA) has 70 - 90 bases– messenger RNA (mRNA) has over 10,000 bases– DNA has over a billion base pairs
• Ribose replaces deoxyribose as the sugar• Uracil replaces thymine as a nitrogenous base• Essential function
– interpret DNA code– direct protein synthesis
Control of Protein Synthesis
• DNA directs the synthesis of enzymes and other proteins– other substances synthesized depend on enzymes – thus indirectly under genetic control
Indirect Control of Nonprotein Synthesis by DNA
Genetic Code• System that enables the 4 nucleotides (A,T,G,C)
to code for the 20 amino acids• Base triplet: TAC
– sequence of 3 DNA nucleotides that codes for 1 amino acid
• Codon: AUG – “mirror-image” sequence in mRNA – there are 64 codons (43)
• AUG codes for methionine, also the start codon• there are 3 stop codons • often 2-3 codons represent the same amino acid
Transcription
• Copy genetic instructions from DNA to RNA• RNA polymerase
– binds to DNA • at site selected by chemical messengers from cytoplasm
– opens DNA helix– transcribes bases from 1 strand of DNA into pre-
mRNA– rewinds DNA helix
Posttranscriptional Modification
• Pre-mRNA contains – exons -“sense” portions– introns -“nonsense portions”
must be removed• Modification
– enzymes remove introns and splice exons together
• Functional mRNA leaves nucleus to be translated
Transfer RNA (tRNA)
• Activation by ATP binds specific amino acid• Anticodon binds to complementary codon of mRNA
Translation of mRNA• Ribosome
– attaches to mRNA– reads mRNA
• start codon (AUG) begins protein synthesis– binds activated tRNA
• Growth of polypeptide chain– reads next codon– binds next tRNA– links amino acids on tRNA’s– releases first tRNA– repeats until stop codon reached
Translation of mRNA Flow Chart
Polyribosome Formation
• Polyribosome– cluster of 10-20 ribosomes reading mRNA at once
• Horizontal filament - mRNA• Large granules - ribosomes• Beadlike chains projecting out - newly formed
proteins
DNA & Peptide Formation
Chaperones and Protein Structure
• As proteins assembled may associate with other proteins - chaperones
• Assists in proper folding of new protein• May escort protein to destination in cell• Stress proteins or heat-shock proteins
– chaperones produced in response to heat or stress – help protein fold back into correct functional shapes
Posttranslational Modification• Signal peptide
– amino acid sequence that causes polyribosome to migrate to rough ER and enters into cisterna
• Modifications in RER cisterna– signal peptide removed, may remove amino acids, fold
protein, form disulfide bridges or add CHO moieties • Transport vesicles
– when modifications are finished, RER pinches off clathrin-coated transport vesicles
• Golgi complex– removes clathrin, further modifies protein in cisterna,
forms tranport vesicles to pass to next cisterna
Packaging and Secretion
• Golgi vesicles– last golgi cisterna releases finished product in
membrane bound golgi vesicles– secretory vesicles
• some golgi vesicles become secretory vesicles, migrate to plasma membrane and release product by exocytosis
– lysosomes• some remain in cell and become lysosomes
Protein Packaging & Secretion
DNA Replication
• DNA unwinds from histones• DNA helicase opens short segment
– point of separation called replication fork• Replication by DNA polymerase
– one strand replicated from replication fork– other strand replicated from opposite direction
DNA Replication
• Semiconservative replication– each new DNA has one new helix and the other helix
conserved from parent DNA
• Each new DNA helix winds around new histones to form nucleosomes
DNA Replication Errors and Mutations
• Error rates– in bacteria 3 errors per 100,000 bases copied– every generation of cells would have 1,000 faulty
proteins• Proofreading and error correction
– after DNA polymerase replicates strand, a smaller polymerase proofreads it and makes corrections
– results in only 1 error per 1,000,000,000 bases copied• Mutations - changes in DNA structure due to
replication errors or environmental factors– some cause no effect, some kill cell, turn it cancerous
or cause genetic defects in future generations
Cell Cycle
• G1 phase, the first gap phase– normal cellular functions
• S phase, synthesis phase– DNA replication
• G2 phase, second gap phase – preparation for mitosis
• replicates centrioles, synthesizes enzymes for cell division
• M phase, mitotic phase– nuclear and cytoplasmic division
• G0 phase, cells that have left the cycle
Functions of Mitosis
• Embryonic development • Tissue growth• Replacement of old and dead cells• Repair of injured tissues
Mitosis: Prophase
• Chromatin supercoils into chromosomes• Nuclear envelope disintegrates• Centrioles sprout microtubules, mitotic spindle• Centrioles move to poles
Metaphase Chromosome
Mitosis: Metaphase
• Chromosomes line up on equator• Spindle fibers attach to centromere• Asters anchor centrioles to plasma membrane
Mitosis: Anaphase
• Centromeres divide• Spindle fibers pull sister chromatids to opposite
poles of cell
Mitosis: Telophase
• Chromatin uncoils• Nuclear envelopes form• Mitotic spindle breaks down
Cytokinesis
• Division of cytoplasm• Myosin pulls on actin in the membrane skeleton• Causes crease around cell equator called
cleavage furrow• Cell pinches in two
Timing of Cell Division
Cells divide when:• Cells large enough• DNA replicated• Adequate supply of nutrients• Growth factor stimulation• Open space in tissueCells stop dividing when:• Loss of growth factors or nutrients• Contact inhibition
Cancer
• Tumors– abnormal growth, when cells multiply faster than
they die– oncology is the study of tumors
• Benign– connective tissue capsule, grow slowly, stays local – potentially lethal by compression of vital tissues
• Malignant– unencapsulated, fast growing, metastatic (causes 90%
of cancer deaths)
Causes of Cancer
• Carcinogens - estimates of 60 - 70% of cancers from environmental agents – chemical
• cigarette tar, food preservatives– radiation
• UV radiation, particles, rays, particles– viruses
• type 2 herpes simplex - uterus, hepatitis B - liver
Mutagens
• Trigger gene mutations– cell may die, be destroyed by immune system or
produce a tumorDefenses against mutagens• Scavenger cells
– remove them• Peroxisomes
– neutralize nitrites, free radicals and oxidizing agents• Nuclear enzymes
– repair DNA• Tumor necrosis factor (TNF) destroys tumors
Cancer Genes
• Oncogenes– mutated form of proto-oncogenes – sis oncogene causes excessive production of growth
factors• stimulate neovascularization of tumor
– ras oncogene codes for abnormal growth factor receptors
• sends constant divide signal to cell
• Tumor suppressor genes– inhibit development of cancer– damage to one or both removes control of cell division
Effects of Malignancies
• Displaces normal tissue, function deteriorates– rapid cell growth of immature nonfunctional cells– metastatic cells different tissue origin
• Block vital passageways– respiratory or vascular
• Diverts nutrients from other tissues– tumors have high metabolic rates– causes weakness, fatigue, emaciation, infection
Chromosomes
• Karyotype– chart of chromosomes at metaphase by size, structure
• Homologous chromosomes– 2 chromosomes in each pair, 1 from each parent– autosomes (22 pairs)– sex chromosomes (X and Y)
• Germ cells - sperm and egg cells, haploid• Somatic cells - all other cells, diploid
Genes and Alleles
• Gene loci– location of gene on chromosome
• Alleles– two homologous chromosomes have same gene at
same locus, may be different forms of gene• Dominant allele
– produces normal, functional protein• Recessive allele
– when both alleles are recessive produces abnormal protein or no protein
Genetics of Earlobes
• Genotype– alleles for a trait (DD)
• Phenotype– trait that results
• Dominant allele (D)– expressed with DD or Dd– Dd parent ‘carrier’ of
recessive gene• Recessive allele (d)
– expressed with dd onlyPunnett square
Multiple Alleles, Codominance, Incomplete Dominance
• Gene pool– collective genetic makeup of whole population
• Multiple alleles– more than 2 alleles for a trait– such as IA, IB, i alleles for blood type
• Codominant– both alleles expressed, IAIB = type AB blood
• Incomplete dominance– phenotype intermediate between traits for each allele
Polygenic Inheritance
• 2 or more genes combine their effects to produce single phenotypic trait, such as skin color
Pleiotropy
• Single gene causes multiple phenotypic traits, as in sickle-cell disease
Sex-Linked Inheritance
• Recessive allele on X, no gene locus for trait on Y, so hemophilia more common in men
Penetrance and Environmental Effects
• Penetrance– % of population to
express predicted phenotype
• Role of environment– brown eye color
requires phenylalanine from diet to produce melanin, the eye pigment
Alleles at the Population Level
• Dominance and recessiveness of allele do not determine frequency in a population
• Some recessive alleles, blood type O, are the most common
• Some dominant alleles, polydactyly, are rare
Recombinant DNA Technique