genes and protein synthesis
DESCRIPTION
Genes and Protein Synthesis. Chapter 7. One Gene-One Polypeptide Hypothesis. DNA contains all of our hereditary information Genes are located in our DNA ~25,000 genes in our DNA (46 chromosomes) Each Gene codes for a specific polypeptide. Main Idea. Central Dogma Francis Crick (1956). - PowerPoint PPT PresentationTRANSCRIPT
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Genes and Protein Synthesis
Chapter 7
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One Gene-One Polypeptide Hypothesis• DNA contains all of
our hereditary information
• Genes are located in our DNA
• ~25,000 genes in our DNA (46 chromosomes)
• Each Gene codes for a specific polypeptide
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Main Idea• Central Dogma– Francis Crick (1956)
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Overall Process• Transcription – DNA to RNA
• Translation – Assembly of
amino acids into polypeptide
– Using RNA
DNA molecule
Gene 1
Gene 2
Gene 3
DNA strand
TRANSCRIPTION
RNA
Polypeptide
TRANSLATIONCodon
Amino acid
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Key Terms • RNA transcription– Initiation,
Elongation, Termination
• TATA box • Introns, Exons• mRNA, tRNA, rRNA• Translation • Ribosome• Codon• Amino Acids• Polypeptide
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DNA RNA
Double stranded Single stranded
Adenine pairs with Thymine Adenine pairs with Uracil
Guanine pairs with Cytosine Guanine pairs with Cytosine
Deoxyribose sugar Ribose sugar
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DNA to Protein • Protein is
made of amino acid sequences
• 20 amino acids
• How does DNA code for amino acid?
DNA molecule
Gene 1
Gene 2
Gene 3
DNA strand
TRANSCRIPTION
RNA
Polypeptide
TRANSLATIONCodon
Amino acid
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Genetic Code• Codon– Three letter code– 5’ to 3’ order– Start codon – Stop codon
• AA are represented by more than one codon
• 61 codons that specify AA
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Amino acids • Abbreviated– Three letters
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Transcription • DNA to RNA• Occurs in nucleus • Three process– Initiation – Elongation – Termination
RNA polymerase
DNA of gene
PromoterDNA Terminator
DNAInitiation
Elongation
TerminationGrowingRNA
RNApolymerase
Completed RNA
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Initiation• RNA polymerase binds to DNA• Binds at promoter region
– TATA box• RNA polymerase unwinds DNA• Transcription unit
– Part of gene that is transcribed• Transcription factors bind to
specific regions of promoter • Provide a substrate for RNA
polymerase to bind beginning transcription
• Forms transcription initiation complex
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Elongation • RNA molecule is
built– RNA polymerase
• Primer not needed• 5’ to 3’ direction • Template strand is
copied– 3’ to 5’ DNA
• Coding strand– DNA strand that is
not copied• Produces mRNA
– Messenger RNA • DNA double helix
reforms
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Termination • RNA polymerase recognizes a termination sequence
– AAAAAAA (polyadenylation)• Nuclear proteins bind to string of UUUUUU on RNA• mRNA molecule releases from template strand
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Post-Transcriptional Modifications• Pre-mRNA
undergoes modifications before it leaves the nucleus
• Poly(A) tail– Poly-A polymerase– Protects from RNA
digesting enzymes in cytosol
• 5’ cap– 7 G’s– Initial attachment
site for mRNA’s to ribosomes
• Removal of introns
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Splicing the pre-mRNA• DNA comprised of – Exons • sequence of DNA or
RNA that codes for a gene
– Introns • non-coding
sequence of DNA or RNA
• Spliceosome– Enzyme that
removes introns from mRNA
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Splicing Process• Spliceosome contains a handful of small
ribonucleoproteins– snRNP’s (snurps)
• snRNP’s bind to specific regions on introns
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Alternative Splicing• Increases number and variety of proteins
encoded by a single gene• ~25,000 genes produce ~100,000 proteins
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Translation• mRNA to protein • Ribosomes read
codons • tRNA assists
ribosome to assemble amino acids into polypeptide chain
• Takes place in cytoplasm
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tRNA• Contains – triplet anticodon – amino acid
attachment site • Are there 61
tRNA’s to read 61 codons?
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tRNA: Wobble Hypothesis • First two nucleotides of
codon for a specific AA is always precise
• Flexibility with third nucleotide
• Aminoacylation– process of adding an AA
to a tRNA – Forming aminoacyl-
tRNA molecule – Catalyzed by 20
different aminoacyl-tRNA synthetase enzymes
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Ribosomes• Translate mRNA chains into amino acids• Made up of two different sized parts – Ribosomal subunits (rRNA)
• Ribosomes bring together mRNA with aminoacyl-tRNAs
• Three sites– A site - aminoacyl– P site – peptidyl– E site - exit
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1 Codon recognition
Amino acid
Anticodon
AsiteP site
Polypeptide
2 Peptide bond formation
3 Translocation
Newpeptidebond
mRNAmovement
mRNA
Stopcodon
Translation process • Three stages– Initiation – Elongation – Termination
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Initiation• Ribosomal subunits associate with mRNA • Met-tRNA (methionine)
– Forms complex with ribosomal subunits• Complex binds to 5’cap and scans for start codon (AUG) (scanning)• Large ribosomal subunit binds to complete ribosome • Met-tRNA is in P-site
Reading frame is established to correctly read codons
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Elongation
• Amino acids are added to grow a polypeptide chain
• A, P, and E sites operate
• 4 Steps
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Termination• A site arrives at a stop codon on mRNA – UAA, UAG, UGA
• Protein release factor binds to A site releasing polypeptide chain
• Ribosomal subunits, tRNA release and detach from mRNA
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ba
Red object = ?
What molecules are present in this photo?
POLYSOME
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Review • What is a gene?• Where is it
located?• What is the main
function of a gene?• Do we need our
genes “on” all the time?
• How do we turn genes “on” or “off”?
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Regulating Gene Expression• Proteins are not
required by all cells at all times
• Regulated• Eukaryotes – 4 ways– Transcriptional (as mRNA
is being synthesized)– Post-transcriptional (as
mRNA is being processed)
– Translational (as proteins are made)
– Post-translational (after protein has been made)
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Transcriptional regulation• Most common• DNA wrapped around histones keep gene promoters
inactive• Activator molecule is used (2 ways)– Signals a protein remodelling complex which loosen the
histones exposing promoter– Signals an enzyme that adds an acetyl group to histones
exposing promoter region
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Transcriptional regulation• Methylation– Methyl groups are added to the cytosine bases in the
promoter of a gene (transcription initiation complex) – Inhibits transcription – silencing– Genes are placed “on hold” until they are needed– E.g. hemoglobin
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Post transcriptional regulation• Pre-mRNA processing
– Alternative splicing• Rate of mRNA
degradation– Masking proteins used to
degrade mRNA – Translation does not occur
• Embryonic development
• Hormones – Casein – milk protein in
mammary gland– When casein is needed,
prolactin is produced extending lifespan of casein mRNA
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Translational regulation• Occurs during
protein synthesis by a ribosome
• Changes in length of poly(A) tail– Enzymes add or
delete adenines – Increases or
decreases time required to translate mRNA into protein
– Environmental cues
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Post-Translational Regulation• Processing
– Removes sections of protein to make it active
– Cell regulates this process (hormones)
• Chemical modification– Chemical groups are
added or deleted – Puts the protein “on hold”
• Degradation– Proteins tagged with
ubiquitin are degraded – Amino acids are recycled
for protein synthesis
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Cancer• Lack regulatory mechanisms • Mutations in genetic code
(mutagens)– Probability increases over lifetime– Radiation, smoking, chemicals
• Mutations are passed on to daughter cells – Can lead to a mass of
undifferentiated cells (tumor)– Benign and malignant
• Oncogenes– Mutated genes that once served
to stimulate cell growth– Cause undifferentiated cell
division
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Genetic Mutations• Positive and negative – Natural selection –
evolution – Cancer –death
• Small-Scale – single base pair– Point mutations • Substitution,
insertion/deletion, inversion
• Large-Scale – multiple base pairs
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Small-Scale Mutations• Four groups – Missense, nonsense, silent, frameshift• Lactose, sickle cell anemia
– SNPs – single nucleotide polymorphisms• Caused by point mutations
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Missense mutation• Change of a single base pair or group of base pairs• Results in the code for a different amino acid • Protein will have different sequence and structure
and may be non-functional or function differently
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Nonsense mutation• Change in single base pair or group of base pairs • Results in premature stop codon • Protein will not be able to function
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Silent Mutation• Change in one or more base pairs• Does not affect functioning of a gene• Mutated DNA sequence codes for same amino acid • Protein is not altered
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Frameshift mutation• One or more nucleotides are inserted/deleted from a DNA
sequence• Reading frame of codons shifts resulting in multiple missense
and/or nonsense effects• Any deletion or insertion of base pairs in multiples of 3 does
not cause frameshift
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Large-scale mutations • Multiple nucleotides,
entire genes, whole regions of chromosomes
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Large-scale mutations • Amplification – gene
duplication– Entire genes are copied to
multiple regions of chromosomes
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Large-scale mutations • Large-scale deletions – Entire coding regions of DNA are removed • Muscular Dystrophy
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Large-scale mutations • Chromosomal translocation– Entire genes or groups of genes are moved from one
chromosome to another – Enhance, disrupt expression of gene
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Large-scale mutations • Inversion– Portion of a DNA molecule reverses its direction in the
genome– No direct result but reversal could occur in the middle of
a coding sequence compromising the gene
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Large-scale mutations • Trinucleotide repeat expansion– Increases number of repeats in genetic code – CAG CAG CAG CAG CAG CAG CAG CAG • Huntingtons disease
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Causes of genetic mutations• Spontaneous mutations– Inaccurate DNA replication
• Induced mutations – Caused by environmental agent – mutagen – Directly alter DNA – entering cell nucleus – Chemicals, radiation
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Chemical Mutagens • Modify individual
nucleotides– Nucleotides
resemble other base pairs
– Confuses replication machinery – inaccurate copying • Nitrous acid
• Mimicking DNA nucleotides – Ethidium bromide –
insert itself into DNA
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Radiation - Low energy • UV B rays • Non-homologous end joining– Bonds form between adjacent nucleotides along DNA
strand – Form kinks in backbone – Skin cancer
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Radiation – high energy • Ionizing radiation – x-ray, gamma rays • Strip molecules of electrons • Break bonds within DNA– Delete portions of chromosomes
• Development of tumors
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Genomes and Gene organization• Human Body– 22 autosomal chromosomes– 1 pair of each sex chromosome (XX, YY)
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Genomes and Gene organization• Components– VNTR’s–variable number tandem repeats (microsatellites)• Sequences of long repeating base pairs• TAGTAGTAGTAGTAG
– LINEs – long interspersed nuclear elements – SINEs – short interspersed nuclear elements – Transposons – small sequences of DNA that move about
the genome and insert themselves into different chromosomes
– Pseudogene – code is similar to gene but is unable to code for protein
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Viruses• Not alive but can replicate themselves• Contain– DNA or RNA– Capsid – protein coat– Envelope – cell membrane
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Virus • 4000 species of virus have been classified
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HIV RNA Replication (Retrovirus) • Reverse
transcriptase to turn RNA into DNA
• Integrase incorporates into our genetic code
• Uses cells parts to make protein parts from mRNA
• genomic RNA
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Influenza A• Viral RNA
replicated and transcribed for protein synthesis
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Virus as Vectors• Transduction– Using a virus vector to insert DNA into a cell or
bacterium