Chapter 12

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 DNA
• Double helix
• “Rungs” are base pairs joined by hydrogen
bonds
• Adenine (A) pairs with thymine (T)
• Cytosine (C) pairs with guanine (G)
• Complementary strands
• Strands oriented in opposite directions
– 5’ to 3’ or 3’ to 5’
• Central dogma
– Transcription – cell
copies DNA to
RNA
– Translation – RNA
information used to
manufacture
proteins
• 3 types of RNA
– Messenger RNA (mRNA) – carries info.
specific to a protein, 3 RNA bases form a
codon specifying an amino acid
– Ribosomal RNA (rRNA) – combines with
proteins to form a ribosome
– Transfer RNA (tRNA) – carries specific amino
acid to ribosome
 Transcription
1. Initiation
– Enzymes unwind DNA exposing template strand
– RNA polymerase binds to promoter
1. Elongation
– RNA polymerase moves 3’ to 5’
1. Termination
– RNA polymerase reaches terminator sequence at
end of gene
– RNA separates – may be mRNA, tRNA or rRNA
– DNA reforms helix
• In bacteria and archaea, ribosomes begin
translating mRNA as soon as transcription
is complete
• In eukaryotes it is usually altered
– 5’ cap and poly A tail added to enhance
translation by helping ribosome attach
– Introns removed leaving exons
 Translation
• Genetic code
– mRNA codon with 3 bases specifies amino acid
– Also contains start and stop codons
• Translation requires
– mRNA – genetic
information specifying
amino acid order in
codons
– tRNA – brings specific
amino acid to
ribosome by pairing
anticodon to mRNA
codon
– Ribosome – rRNA and
proteins
• 3 steps in translation
1. Initiation
– mRNA start codon binds to small ribosomal subunit
– 1st tRNA binds to mRNA codon
1. Elongation
– Large ribosomal subunit attaches
– tRNA corresponding to 2nd codon attaches
– Covalent bond forms between amino acids
– Ribosome release empty 1st tRNA
– Ribosome shift down one codon allowing 3rd tRNA to
bind
– Polypeptide grows one amino acid at a time
1. Termination
– Stop codon reached
– New polypeptide released
• Protein folding
– Must achieve final functional shape – some
regions attract or repel, enzymes catalyze
bonding, “chaperone” proteins stabilize
– Errors in folding can lead to illness
– Some proteins must be altered
• Insulin has amino acids removed
• Hemoglobin has 4 separate polypeptides
 Regulation
• Protein synthesis is
fast and efficient
• Tremendous ATP
requirement
• Cells save energy
by not producing
unneeded proteins
• Operons in bacteria
– Group of genes plus promoter and operator
that control transcription of group
– Promoter – where RNA polymerase attaches
– Operator – DNA sequence where repressor
can bind to inhibit transcription
– Lac operon – 3 lactose degrading enzymes
plus promoter and repressor
• Without lactose repressor turns genes off
• Eukaryotes more
complex
– Signal transduction
can activate or
deactivate
transcription factors
– Additional
regulatory
mechanisms
• Methylation
• Alternative splicing
• Many others
 Mutations
• Change in cell’s DNA
sequence
• Can be good, bad, or
silent
• Point mutations
– Substitute one DNA
base for another
– “Silent” is same amino
acid specified
– May cause disease –
sickle cell anemia
• Base insertions and
deletions
– Frameshift mutation
caused by addition or
deletion by any
number other than a
multiple of 3
– Expanding repeat –
number of copies of 3
or 4 nucleotide
sequence increases
over several
generations
• Causes of mutation
– Spontaneous – DNA
replication error
– Meiotic error –
duplication or deletion
– Chromosome inversion
and translocations
– Transposons –
moveable DNA
sequences
– Mutagen – external
agent – radiation,
chemicals
• Heritable mutations
– Somatic mutations occur in nonsex cells
• All cells derived from that cell carry mutation
• Not passed to offspring
– Germline mutation
• Heritable – passed in every gamete
• Mutations are important
– Create new gene variants (alleles)
– Random mutations results in antibiotic resistant
bacteria
 Human Genome Project
• 3.2 billion base pairs
• 25,000 genes produce 400,000 different
proteins
– Removing different combinations of introns
makes different proteins
• Only about 1.5% of genome encodes
protein
– 98.5% encodes regulatory sequences,
pseudogenes, and transposons
• Transgenic organism
receives recombinant
DNA
• Recombinant DNA –
genetic material
spiced together from
multiple organisms
• Transgenic bacteria
make drugs
• Transgenic crops
resist disease
• Transgenic human
disease models
 Biotechnology
• Gene therapy – replacing faulty genes
• Block gene expression to silence harmful
gene or study gene function
– Antisense RNA, gene knockouts
• DNA microarrays or DNA chips – use
collection of known DNA sequences
• Proteomics – genome changes little but
proteins different in different cells and
different times
 Investigating life: Clues to
the origin of language
• Family with unusual language disorder traced to
mutation of single gene on chromosome 7
• FOXP2 not solely responsible for language
acquisition but a transcription factor can affect
muscle control and brain function
• Compared amino acid sequence in humans,
primates and mice
• Nearly every human homozygous for same
FOXP2 allele
• Estimate original mutation happened 200,000
years ago