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 RBCs) 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

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Nitrogenous Bases
Purines - double carbonnitrogen 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
Sugar-phosphate backbone Segment of DNA Sugar-phosphate backbone

Law of complementary base pairing

one strand determines base sequence of other

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 premRNA 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 tRNAs 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 tissue Cells 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 tumor

Defenses 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 only

Punnett 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