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Chapter 4
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Genetics and Cellular Function
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Genes and nucleic acids
Protein synthesis and secretion
DNA replication and the cell cycle
Chromosomes and heredity
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Organization of the Chromatin
• Threadlike chromatin =
chromosomes = 46 DNA
molecules and associated
proteins
• Nondividing state = DNA
molecules compacted
– coiled around core particle (histone
protein)
– zig-zagged, looped and coiled onto
itself
• Preparing to divide
– DNA copies itself to form 2 parallel
sister chromatids
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Chromatin Structure
4-4
DNA Structure: Twisted Ladder
DNA molecule described as double helix.
4-5
Nucleotide Structure
• DNA = polymer of
nucleotides
• Each nucleotide consist of
– phosphate group
– sugar
• ribose (RNA)
• deoxyribose (DNA)
– nitrogenous base
• in this picture = adenine
4-6
Nitrogenous Bases
• Purines - double ring
– guanine
– adenine
• Pyrimidines - single
ring
– uracil - RNA only
– thymine - DNA only
– cytosine – both
• DNA bases =CTAG
• RNA bases = CUAG
4-7
Complementary Base Pairing
• Nitrogenous bases
united by hydrogen
bonds
• DNA base pairings
– A-T and C-G
• Law of complementary
base pairing
– one strand determines
base sequence of other
Segment of DNA
4-8
DNA Function
• Code for protein synthesis
• Gene - sequence of DNA nucleotides
that codes for one protein
• Genome - all the genes of one person
– humans have estimated 30-35,000 genes
– other 98% of DNA noncoding – “junk” or
regulatory
4-9
Discovery of the Double Helix
• By 1900:components of DNA were known
– sugar, phosphate and bases
• By 1953: x ray diffraction determined geometry
of DNA molecule
• Nobel Prize awarded in 1962 to 3 men: Watson,
Crick and Wilkins but not to Rosalind Franklin
who died of cancer at 37 getting the x ray data
that provided the answers.
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RNA: Structure and Function
• RNA smaller than DNA (fewer bases)
– transfer RNA (tRNA) 70 - 90 bases
– messenger RNA (mRNA) over 10,000 bases
– DNA has over a billion base pairs
• Only one nucleotide chain (not a helix)
– ribose replaces deoxyribose as the sugar
– uracil replaces thymine as a nitrogenous base
• Essential function
– interpret DNA code
– direct protein synthesis in the cytoplasm
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Genetic Control of Cell Action
through Protein Synthesis
• DNA directs the synthesis of all cell proteins
– including enzymes that direct the synthesis of
nonproteins
• Different cells synthesize different proteins
– dependent upon differing gene activation
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Preview of Protein Synthesis
• Transcription
– messenger RNA (mRNA) is formed next to
an activated gene
– mRNA migrates to cytoplasm
• Translation
– mRNA code is “read” by ribosomal RNA
as amino acids are assembled into a
protein molecule
– transfer RNA delivers the amino acids to
the ribosome
4-13
Genetic Code
• System that enables the 4 nucleotides (A,T,G,C)
to code for the 20 amino acids
• Base triplet:
– found on DNA molecule (ex. TAC)
– nucleotides that stand for 1 amino acid
• Codon:
– “mirror-image” sequence of nucleotides found in
mRNA (ex AUG)
– 64 possible codons (43)
• often 2-3 codons represent the same amino acid
• start codon = AUG
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• 3 stop codons = UAG, UGA, UAA
Transcription
• Copying instructions from DNA to RNA
– RNA polymerase binds to DNA
• at site selected by chemical messengers from
cytoplasm
– opens DNA helix and transcribes bases from
1 strand of DNA into pre-mRNA
• if C on DNA, G is added to mRNA
• if A on DNA, U is added to mRNA, etc.
– rewinds DNA helix
• Pre-mRNA is unfinished
– “nonsense” (introns) removed by enzymes
– “sense” (exons) reconnected and exit
nucleus
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Alternative Splicing of mRNA
• One gene can code for more than one
protein
• Exons can be spliced together into a
variety of different mRNAs.
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Translation of mRNA
• mRNA begins with leader sequence
– binding site for ribosome
• Start codon AUG
4-17
Steps in Translation of mRNA
• Converts alphabet of nucleotides into a
sequence of amino acids to create a
specific protein
• Ribosome in cytosol or on rough ER
– small subunit attaches to mRNA leader sequence
– large subunit joins and pulls mRNA along as it
“reads” it
• start codon (AUG) where protein synthesis begins
– small subunit binds activated tRNA with
corresponding anticodon
– large subunit enzyme forms peptide bond
4-18
Steps in Translation of mRNA
• Growth of polypeptide chain
– next codon read, next tRNA attached,
amino acids joined, first tRNA released,
process repeats and repeats
• Stop codon reached and process
halted
– polypeptide released and ribosome
dissociates into 2 subunits
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Transfer RNA (tRNA)
• Activation by ATP binds specific amino acid and
provides necessary energy to join amino acid to
growing protein molecule
• Anticodon binds to complementary codon of
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mRNA
Polyribosomes
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Polyribosomes and Signal
Peptides
• Polyribosome
– cluster of 10-20 ribosomes reading mRNA at one
time
– horizontal filament - mRNA
– large granules - ribosomes
– beadlike chains projecting out - newly formed
proteins
• takes 20 seconds to assemble protein of 400 amino
acids
• cell may produce > 150,000 proteins/second
• Signal peptide = beginning of chain of amino
acids
– determines protein’s destination within cell
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DNA and Peptide Formation
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Chaperones and Protein
Structure
• Newly forming protein molecules must
coil or fold into proper 2nd and tertiary
molecular structure
• Chaperone proteins
– prevent premature folding, assist in proper
folding and escort protein to final
destination
• Stress or heat-shock proteins
– produced in response to heat or stress
– help damaged protein fold back into
correct functional shapes
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Protein Packaging and Secretion
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Posttranslational Modification
in Rough ER
• Proteins destined for secretion or packaging are
assembled on rough ER and sent to Golgi
complex
• Signal peptide
– drags new protein from ribosome through pore into
cisterna of ER
• Posttranslational modification of protein in ER
– remove some amino acids, fold the protein adding
disulfide bridges or adding carbohydrates
• Rough ER pinches off transport vesicles
– fuse with and empty into nearest Golgi complex
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Posttranslational Modification
in Golgi Complex
• Protein modified in cisterna, passed to
next cisterna
• Last golgi cisterna releases finished
product as membrane bound vesicles
– secretory vesicles
• migrate to plasma membrane and release
product by exocytosis
– lysosomes
• vesicles that remain in cell
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DNA Replication 1
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DNA Replication 2
• Law of complimentary base pairing allows
building of one DNA strand based on the
bases in 2nd strand
• Steps of replication process
– DNA helicase opens short segment of helix
• replication fork is point of separation of 2 strands
– DNA polymerase assembles new strand of
DNA next to one of the old strands
• 2 DNA polymerase enzymes at work
simultaneously
4-29
DNA Replication 3
• Semiconservative replication
– each new DNA molecule contains one new
helix and one conserved from parent DNA
• Additional histones made in cytoplasm
• Each DNA helix winds around histones to
form nucleosomes
• 46 chromosomes replicated in 6-8 hours by
1000’s of polymerase molecules
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Errors and Mutations
• Error rates of DNA polymerase
– in bacteria, 3 errors per 100,000 bases copied
• Proofreading and error correction
– a small polymerase proofreads each new DNA
strand 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
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Cell Cycle
• G1 phase, the first gap phase
– accumulates materials needed
to replicate DNA
• S phase, synthesis phase
– DNA replication
• G2 phase, second gap phase
– replicates centrioles
– synthesizes enzymes for division
• M phase, mitotic phase
– nuclear and cytoplasmic division
• G0 phase, cells that have left the cycle
• Cell cycle duration varies between cell types
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Mitosis
• one cell divides into 2 daughter cells
with identical copies of DNA
• Functions of mitosis
– embryonic development
– tissue growth
– replacement of dead cells
– repair of injured tissues
• Phases of mitosis (nuclear division)
– prophase, metaphase, anaphase, telophase
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Mitosis
4-34
Mitosis: Prophase 1
• Chromatin coils into genetically
identical, paired, sister
chromatids
– each chromatid contains a DNA
molecule
– remember: genetic material (DNA)
was doubled during S phase of
interphase
• Thus, there are 46
chromosomes with 2
chromatids/chromosome and 1
molecule DNA per chromatid.
4-35
Mitosis: Prophase 2
• Nuclear envelope disintegrates
• Centrioles sprout microtubules that
push them apart and towards each pole
of the cell
– spindle fibers grow towards chromosomes
• attach to kinetochore on side of centromere
– spindle fibers pull chromosomes towards
cell equator
4-36
Mitosis: Metaphase
• Chromosomes line up on one equator
• Mitosis spindles finished
– spindle fibers (microtubules) attach
centrioles to long centromere
– shorter microtubules anchor centrioles to
plasma membrane (aster)
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Mitosis: Anaphase
• Enzyme splits 2 chromatids apart at
centromere
• Daughter chromosomes move towards
opposite poles of cells with centromere
leading the way
– motor proteins in kinetochore move
centromeres along spindle fibers as fibers
are disassembled
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Mitosis: Telophase
• New nuclear envelopes formed by
rough ER
• Chromatids uncoil into chromatin
• Mitotic spindle breaks down
• Nucleus forms nucleoli
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Cytokinesis
• Division of cytoplasm into 2 cells
– overlaps telophase
• Myosin pulls on microfilaments of actin
in the membrane skeleton
– creates crease around cell equator called
cleavage furrow
• Cell pinches in two
– interphase has begun
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Timing of Cell Division
Cells divide when:
• Have enough cytoplasm for 2 daughter
cells
• DNA replicated
• Adequate supply of nutrients
• Growth factor stimulation
• Open space due to neighboring cell death
Cells stop dividing when:
• Loss of growth factors or nutrients
• Contact inhibition
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Chromosomes and Heredity
• Heredity = transmission of genetic
characteristics from parent to offspring
– karyotype = chart of chromosomes at metaphase
• 23 pairs homologous chromosomes in somatic
cells (diploid number of chromosomes)
– 1 chromosome inherited from each parent
– 22 pairs called autosomes
– one pair of sex chromosomes (X and Y)
• normal female has 2 X chromosomes
• normal male has one X and one Y chromosome
• Sperm and egg contain only 23 chromosomes
– fertilized egg has diploid number of chromosomes4-42
Karyotype of Normal Male
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The Genome
• Human Genome project (1990-2003)
– mapped entire base sequence (A,T,C,G) of 99% of our DNA
• Genomics – study of how your DNA affects structure
and function
– Homo sapiens have 35,000 genes
– these genes generate millions of different proteins with
alternative splicing
• All humans 99.99% genetically identical
• Genomic medicine
– Prediction, diagnosis and treatment of disease using
knowledge of genome
• Gene-substitution therapy
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Genes and Alleles
• Locus = location of particular gene
• Alleles
– different forms of gene at same locus on 2
homologous chromosomes
• Dominant allele (D)
– produces protein responsible for visible trait
• Recessive allele (d)
– expressed only when both alleles are
recessive
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Genetics of Earlobes
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Genetics of Earlobes
• Genotype
– alleles for a particular trait
(DD)
• Phenotype
– trait that results (appearance)
• Homozygous – 2 identical
alleles at a particular gene
• Heterozygous – different
alleles for a particular gene
• Carriers of hereditary
disease (cystic fibrosis)
– heterozygous individual
Punnett square 4-47
Multiple Alleles and Dominance
• Gene pool
– collective genetic makeup of 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
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Polygenic Inheritance
• 2 or more loci contribute to a single
phenotypic trait (skin and eye color,
alcoholism and heart disease)
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Pleiotropy
• One gene produces multiple phenotypic
effects
– Alkaptonuria = mutation that blocks the
breakdown of tyrosine
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Sex-Linked Inheritance
• Recessive hemophilic allele on X, no gene locus
for trait on Y, so hemophilia more common in
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men (mother is carrier)
Penetrance and Environmental
Effects
• Penetrance
– % of population
expressing predicted
phenotype
• Role of environment
– brown eye color
requires
phenylalanine from
diet to produce
melanin pigment
4-52
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 and
blood type AB, are rare
4-53
Cancer
• Tumors (neoplasms)
– abnormal growth, cells multiply faster than
they die
– oncology = study of tumors
• Benign
– connective tissue capsule, slow growth,
stays local
– potentially lethal by compression of vital
tissues
• Malignant tumor = cancer
– unencapsulated, fast growing, metastatic
(spreading), stimulate angiogenesis
4-54
Causes of Cancer
• Carcinogens - estimates of 60 - 70%
of cancers from environmental
agents
– chemical = cigarette tar, food
preservatives, industrial chemicals
– radiation
– Viruses = type 2 herpes simplex uterus, hepatitis C - liver
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Carcinogens (Mutagens)
• Trigger gene mutations
– cell may die, be destroyed by immune system or
produce a tumor
• Defenses against mutagens and tumors
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scavenger cells - remove mutagens
peroxisomes - neutralize mutagens
nuclear enzymes - repair damaged DNA
macrophages and monocytes secrete tumor
necrosis factor (TNF) - destroys tumors
– natural killer cells destroy malignant cells during
immune surveillance
4-56
Malignant Tumor Genes
• Oncogenes
– mutated form of normal growth factor genes
called proto-oncogenes
– sis oncogene causes excessive production of
growth factors
– ras oncogene codes for abnormal growth
factor receptors
• Tumor suppressor genes
– inhibit development of cancer
– damage to one or both removes control of cell
division
4-57
Effects of Malignancies
• Displaces normal tissue and organ
function deteriorates
– cell growth of immature nonfunctional cells
• Block vital passageways
– block air flow or rupture blood vessels
• Diverts nutrients from healthy tissues
– tumors have high metabolic rates
– causes weakness, fatigue, emaciation,
susceptibility to infection
– cachexia is extreme wasting away of muscle
4-58
and adipose tissue