SlideShare una empresa de Scribd logo
1 de 70
Descargar para leer sin conexión
Molecular Genetics
       Part II
 From Gene to Protein
History
• Archibald Garrod – 1909
• First to suggest that genes dictate
  phenotype through production of
  proteins
• Believed that genetic diseases resulted
  from the inability to make particular
  enzymes
• “Inborn errors of metabolism”
One Gene – One Enzyme
• Beadle & Ephrussi – 1930’s
• Studied mutations affecting eye color in
  Drosophila
• Concluded that each mutation blocks
  pigment synthesis at a specific step by
  preventing production of the enzyme that
  catalyzes that step
• Specific pathways were not known, so
  results were inconclusive
Beadle & Tatum
• Treated Neurospora (a mold) with X-rays
• Looked for mutations in nutritional requirements
  – Wild type Neurospora grows on minimal medium (agar
    enriched with a few nutrients)
  – All mutants will grow on complete medium (agar plus all 20
    amino acids & other nutrients)
• Identified the specific amino acid required for growth
  by each mutant
  – That identified the defective synthetic pathway
  – Looked at each intermediate step in the blocked synthetic
    pathway
• Concluded that mutation in a single gene blocked
  production of a single enzyme
Molecular  genetics partii 100131193902-phpapp01
One Gene – One Polypeptide
• Not all proteins are enzymes
• Can extend one gene = one enzyme
  doctrine to one gene = one polypeptide
• Many proteins are comprised of two or
  more polypeptides
Central Dogma
• How does the sequence of a strand of DNA
  correspond to the amino acid sequence of a
  protein?
• The central dogma of molecular biology, states
  that:
Transcription & Translation
• DNA is first copied (transcribed) to an
  RNA intermediate
• The RNA intermediate is then translated
  to protein
• Why have an intermediate between
  DNA and the proteins it encodes?
Why RNA?
• The DNA remains protected in the nucleus,
  away from caustic enzymes in the
  cytoplasm.
• Gene information can be amplified
  – Many copies of an RNA can be made from one
    copy of DNA.
• Greater regulation of gene expression
  – Specific controls can act at each step in the
    pathway between DNA and proteins.
  – The more elements there are in the pathway, the
    more opportunities there are for control
What is RNA?
• RNA has the same primary structure as DNA
  – consists of a sugar-phosphate backbone, with
    nucleotides attached to the 1' C of the sugar.
• Differences between DNA and RNA :
  – Contains the sugar ribose instead of
    deoxyribose
  – The nucleotide, uracil, is substituted for
    thymine
  – RNA exists as a single-stranded molecule.
     • Because of the extra hydroxyl group on the sugar,
       RNA is too bulky to form a a stable double helix.
     • Regions of double helix can form where there is
       some base pair complementation resulting in hairpin
       loops.
Types of RNA
• mRNA - messenger RNA
  – A copy of a gene.
  – Has a sequence complementary to one strand of
    the DNA & identical to the other strand.
  – Carries the information stored in DNA in the
    nucleus to the ribosomes in the cytoplasm where
    protein is made.
• tRNA - transfer RNA
  – A small RNA with a very specific structure that
    can bind an amino acid at one end, and mRNA at
    the other end.
  – Acts as an ‘adaptor’ to carry & attach amino acids
    to the appropriate place on the mRNA.
Types of RNA (Cont.)
• rRNA - ribosomal RNA
  – One of the structural components of the
    ribosome.
  – Has a sequence complimentary to regions of
    the mRNA
  – Allows ribosome to bind to an mRNA
• snRNA - small nuclear RNA
  – Is involved in the machinery that processes
    RNA's as they travel between the nucleus and
    the cytoplasm.
The Genetic Code
• How does mRNA specify an amino acid
  sequence?
• It would be impossible for each amino acid to
  be specified by one nucleotide
  – there are only 4 nucleotides and 20 amino acids.
  – two nucleotide combinations could only specify 16
    amino acids.
• Each amino acid is specified by a
  combination of three nucleotides, called a
  codon
Molecular  genetics partii 100131193902-phpapp01
Molecular  genetics partii 100131193902-phpapp01
The Code is Redundant, Not
             Ambiguous
• Each amino acid may be specified by up to six
  codons
  – In many cases, codons that are synonyms differ only in
    the third base of the triplet
• Different organisms have different frequencies of
  codon usage.
  – A giraffe might use CGC for arginine much more often
    than CGA, and the reverse might be true for a sperm
    whale.
• Some codons specify “stop” (or “start)
• There is no ambiguity
  – the same codon ALWAYS codes for the same amino acid
Codons & Anticodons
• How do tRNAs recognize to which codon
  to bring an amino acid?
• The tRNA has an anticodon on its mRNA-
  binding end
• The anticodon is complementary to the
  codon on the mRNA.
• Each tRNA only binds the appropriate
  amino acid for its anticodon
t-RNA Structure
Transcription
• How does the sequence information from
  DNA get transferred to mRNA?
• How is this information carried to the
  ribosomes in the cytoplasm?
• This process is called transcription
• Highly similar to DNA replication.
• Different enzymes are used in
  transcription.
• The most important is RNA polymerase
RNA Polymerase
• RNA polymerase is a holoenzyme
  – an agglomeration of many different factors
• Together, direct the synthesis of mRNA
• Pries the DNA strands apart
• Strings complimentary RNA nucleotides on the
  DNA template
• Like DNA polymerase, can only add to the 3’ end
• So only one mRNA is made, elongating 5’  3’
Stages of Transcription
• Initiation
• Elongation
• Termination
Molecular  genetics partii 100131193902-phpapp01
Initiation
• RNA polymerase must recognize the beginning of
  a gene to know where to start synthesizing mRNA.
• One part of the enzyme has a high affinity for a
  particular DNA sequence that appears at the
  beginning of genes.
• The sequence where RNA polymerase attaches to
  the DNA and begins transcription = the promoter
  – a unidirectional sequence on one strand of the DNA
• Tells RNA polymerase both where to start and in
  which direction (that is, on which strand) to
  continue synthesis.
The Promoter
• In prokaryotes, RNA polymerase recognizes
  and binds the promoter
• The bacterial promoter almost always
  contains some version of the following
  elements:
Eukaryotic Promoters
• In eukaryotes special proteins, transcription factors,
   mediate binding RNA polymerase and the
  promoter
• RNA polymerase binds to the promoter only after
  transcription factors bind
• Transcription factors + RNA polymerase, bound to
  the promoter = transcription initiation complex
• Eukaryotic promoters usually include a TATA box
   – A nucleotide sequence containing TATA about
     25 nucleotides prior to the start point
Molecular  genetics partii 100131193902-phpapp01
Elongation
• The RNA polymerase stretches open the
  double helix at the start point in the DNA
  and begins synthesis of a complementary
  RNA strand on one of the DNA strands
• The RNA polymerase recruits RNA
  nucleotides in the same way that DNA
  polymerase recruits dNTPs.
• Since synthesis only proceeds in the 5' to 3'
  direction, there is no need for Okazaki
  fragments.
Molecular  genetics partii 100131193902-phpapp01
Sense & Antisense
• Synthesis only occurs in the 5’ to 3’ direction
• In transcription, only one DNA strand is
  copied
• We call the strand that is copied the
  antisense or template strand
• The other strand, which is identical to the
  mRNA made (substituting U for T), is the
  sense or coding strand.
Termination of Transcription
• How does RNA polymerase know when to stop
  transcribing a gene?
• Sequence that signals the end of transcription =
  terminator
• RNA polymerase transcribes the terminator
  – The transcribed terminator actually ends the process
• In prokaryotes there is no nucleus, so ribosomes can
  begin making protein from an mRNA immediately
• The terminator sequence of the mRNA allows it to
  form a hairpin loop, which blocks the ribosome.
  – The ribosome falls off the mRNA,
  – That signals termination by the RNA polymerase.
  – RNA polymerase falls off the DNA and transcription
Eukaryotic Termination
• RNA polymerase continues for hundreds of
  nucleotides beyond the termination signal
• AAUAAA
• At a point 10 to 35 nucleotides past the
  AAUAAA, the forming m-RNA is cut free
• The cleavage site is the point of addition of
  a poly-A tail
Post Transcription
               Modification
• In eukaryotes, enzymes modify pre-mRNA before
  it is sent to the cytoplasm
• Both ends of the transcript are altered
• The 5’ end is capped with modified guanine
  – Protects mRNA from degradation
  – Helps attach the ribosome
• At the 3’ end an enzyme makes a poly-A tail
  formed from 50 to 250 adenine nucleotides
  – Inhibits degradation and helps ribosome attach
  – May also help export mRNA out of the nucleus
• Interior sections are cut out, and the remaining
  parts are spliced together
RNA Processing
Introns & Exons
• Most eukaryotic genes and their RNA
  transcripts have long noncoding stretches of
  nucleotides = introns
• Noncoding sequences are interspersed
  between coding sections
• Coding sections = exons
• That is, the sequence of eukaryotic DNA that
  codes for a polypeptide is not continuous
• RNA polymerase transcribes both introns and
  exons
RNA Splicing
• Introns are cut out and exons are spliced
  together before mRNA exits the nucleus
• Short nucleotide sequences at the end of
  introns are signals for RNA splicing
• Small nuclear ribonucleoproteins
  (snRNPs) recognize splice sites
  – Composed of snRNA & protein
• Several snRNPs and additional proteins
  form a complex = spliceosome
• At splice sites at the end of an intron, cuts
  out the intron and fuses the exons
The Spliceosome
Why Introns?
• Introns may play regulatory role in the cell
• Split genes allow a single gene to code more
  than one kind of polypeptide
• Outcome depends on which sections are
  treated as exons during RNA processing
   – Alternative RNA splicing
• May facilitate evolution of new proteins
• Increase possibility of potentially beneficial
  crossing-over of genes
Molecular  genetics partii 100131193902-phpapp01
Translation
• How do messenger RNAs direct protein
  synthesis?
• The message encoded in the mRNA is an
  amino acid sequence
• mRNA travels to ribosome in the
  cytoplasm, where the message is read
• The specified amino acids are assembled
  on the mRNA template on the ribosome
• Enzymes help form the sequenced amino
  acids into a polypeptide
Molecular  genetics partii 100131193902-phpapp01
The Ribosome
• The cellular factory where proteins are synthesized
• Consists of structural RNA and ~ 80 different proteins.
• In its inactive state, it exists as two subunits
   – a large subunit and a small subunit.
• When the small subunit encounters an mRNA, it
  begins translation of the mRNA to protein.
• There are three sites in the large subunit
   – The A site accepts a new tRNA bearing an amino
     acid
   – the P site bears the tRNA attached to the growing
     chain.
   – The E site contains the exiting tRNA
Molecular  genetics partii 100131193902-phpapp01
Charging the tRNA
• tRNA (transfer RNA) acts as a translator between
  mRNA and protein
• Each tRNA has a specific anticodon and an amino
  acid acceptor site.
• Each tRNA also has a specific charger protein;
   – This protein can only bind to that particular
     tRNA and attach the correct amino acid to the
     acceptor site.
   – These charger proteins are called aminoacyl
     tRNA synthetases
• The energy to make this bond comes from ATP.
Molecular  genetics partii 100131193902-phpapp01
Aminoacyl-tRNA Synthases
• Each tRNA must match with the correct amino acid
  – Each tRNA must attach only the amino acid specified by
    the mRNA codon to which the tRNA anticodon binds
• The amino acid is joined to the tRNA by an
  aminoacyl-tRNA synthase
  – There are 20 of these enzymes; one for each amino acid
• Catalyzes the covalent bond between the amino acid
  and tRNA
• The active site of each aminoacyl-tRNA synthase fits
  only a specific amino acid and tRNA
• Once the amino acid is bound, the tRNA is
  aminoacyl tRNA
Molecular  genetics partii 100131193902-phpapp01
Wobble
• If there was one tRNA for each mRNA
  codon, there would be 61 different tRNAs
• Actually, there are fewer
• Some tRNAs have anticodons that
  recognize 2 or more different codons
• Base pairing rules between the third base of
  a codon and its tRNA anticodon are not a
  rigid as DNA to mRNA pairing
  – Example: U in tRNA can pair with either A or T
    in the third position of an mRNA codon
• This flexibility is called wobble
Molecular  genetics partii 100131193902-phpapp01
Initiation of Translation
• The start signal for translation is the codon
  ATG
  – Codes for methionine.
  – Not every protein starts with methionine,
  – Often this first amino acid will be removed in
    post-translational processing.
• A tRNA charged with methionine binds to the
  translation start signal.
• The large subunit binds to the mRNA and the
  small subunit
• Elongation begins.
Molecular  genetics partii 100131193902-phpapp01
Elongation of the New Protein
• After the first charged tRNA appears in the A site, the
  ribosome shifts so that the tRNA is in the P site.
• New charged tRNAs, corresponding the codons of
  the mRNA, enter the A site, and a peptide bond is
  formed between the two amino acids.
• The first tRNA is now released
• The ribosome shifts again so that a tRNA carrying
  two amino acids is now in the P site
• A new charged tRNA can bind to the A site.
• This process of elongation continues until the
  ribosome reaches a stop codon.
Molecular  genetics partii 100131193902-phpapp01
Termination of the Protein
• When the ribosome reaches a stop
  codon, no aminoacyl tRNA binds to the
  empty A site.
• This is the ribosome’s signal to break
  into its large and small subunits,
• Releasing the new protein and the
  mRNA.
Molecular  genetics partii 100131193902-phpapp01
Polyribosomes
• A single mRNA can be used to make
  many copies of a polypeptide at the
  same time
• Multiple ribosomes can read the same
  mRNA strand, like beads on a string
• These strings are called polyribosomes
Polyribosomes
Post-Translational Processing
• This isn't always the end of the story for the new
  protein.
• Often it will undergo post-translational modifications.
• Modifications include:
• Cleavage by a proteolytic (protein-cutting) enzyme at
  a specific place.
• Having some amino acids altered.
   – For example, a tyrosine residue might be phosphorylated.
• Become glycosylated.
   – Many proteins have carbohydrates covalently attached to
     asparagine residues.
Molecular  genetics partii 100131193902-phpapp01
Mutations
•   What kinds of errors can occur in DNA?
•   What causes them?
•   What are their effects?
•   Types of mutations:
    – Chromosomal mutations
    – Point mutations
    – Frameshift mutations
Molecular  genetics partii 100131193902-phpapp01
Chromosomal Mutations
• Mutations that occur at a macroscopic
  level.
• Large sections of chromosomes can be
  altered or shifted, leading to changes in
  the way genes are expressed.
• Types of chromosomal mutations:
  –   Translocations
  –   Inversions
  –   Deletions
  –   Nondisjunction
Translocations & Inversions
• Translocation
  – The interchange of large segments of DNA
    between two chromosomes.
  – Can change gene expression if a gene is at the
    translocation breakpoint or if it is reattached so that
    it is incorrectly regulated
• Inversion
  – Occurs when a region of DNA flips its orientation
    with respect to the rest of the chromosome.
  – Rotates, end for end
  – This can lead to the same problems as
    translocations.
Deletions & Nondisjunction
• Deletion
  – Sometimes large regions of a chromosome are deleted.
  – This can lead to a loss of important genes.
• Nondisjunction
  – Sometimes chromosomes do not divide correctly in cell
    division
  – When large regions of a chromosome are altered (such as
    translocation), the chromosome may not segregate properly
    during cell division
  – One daughter cell will end up with extra genetic material,
    one will end up with less than its share
  – This is called nondisjunction.
  – When there are extra or too few copies of a gene, the cell
    will have problems
Point Mutations
• Point mutations are single base pair changes.
• Three possible outcomes:
• Nonsense mutation
  – Creates a stop codon where none previously existed.
  – This shortens the resulting protein, possibly removing
    essential regions.
• Missense mutation
  – Changes the code of the mRNA.
  – Which changes the resulting amino acid
  – This may alter the shape and properties of the protein.
• Silent mutation
  – Has no effect on protein sequence.
  – Because the genetic code is redundant, some changes
    have no effect
Molecular  genetics partii 100131193902-phpapp01
Frameshift Mutations
• Insertions or deletions have a disastrous
  effect
• mRNA is “read” as a series of three letter
  words
• Insertions or deletions that are not
  multiples of three, shift the reading frame
Frameshift Example
• Given the coding sequence:
            AGA UCG ACG UUA AGC
• corresponding to the protein:
    arginine - serine - threonine - leucine - serine
• The insertion of a C-G base pair between bases 6
  and 7 would result in the following new code:
            AGA UCG CAC GUU AAG C
• which would result in a non-functional protein:
  arginine - serine - histidine - valine - lysine
• Every amino acid after the insertion will be wrong.
• The frame shift might even generate a stop codon
  which would prematurely end the protein.
Molecular  genetics partii 100131193902-phpapp01
DNA Repair
• If replication of DNA proceeded as was described
  previously, DNA polymerase would make a
  mistake on average about every 1000 base pairs.
• This level would be unacceptable, because too
  many genes would be rendered non-functional.
• Organisms have elaborate DNA proofreading and
  repair mechanisms, which can recognize false
  base-pairing and DNA damage, and repair it.
• The actual error rate is more in the region of one
  in a million to one in a billion.
The Beauty of Mutations
• Why mutations?
• Our environment constantly changes, the Earth
  and its ecosystems change.
• Populations must change to survive
• Evolutionary change requires variation, the raw
  material on which natural selection works
• One mechanism for variation and change is at the
  DNA level.
• Mutations can be beneficial and enable the
  organism to adapt to a changing environment.
• However, most mutations are deleterious, and
  cause varied genetic diseases

Más contenido relacionado

La actualidad más candente

Transcription in prokaryotes
Transcription in prokaryotesTranscription in prokaryotes
Transcription in prokaryotesKaayathri Devi
 
Regulation of gene expression
Regulation of gene expressionRegulation of gene expression
Regulation of gene expressionSurendraMarasini1
 
Gene expression & protein synthesis
Gene expression & protein synthesisGene expression & protein synthesis
Gene expression & protein synthesisssuserc4adda
 
Introduction to Transcription
Introduction to TranscriptionIntroduction to Transcription
Introduction to TranscriptionPrasanna R Kovath
 
Post transcriptional modifications
Post transcriptional modificationsPost transcriptional modifications
Post transcriptional modificationsPrasanna R Kovath
 
transcription activators, repressors, & control RNA splicing, procesing and e...
transcription activators, repressors, & control RNA splicing, procesing and e...transcription activators, repressors, & control RNA splicing, procesing and e...
transcription activators, repressors, & control RNA splicing, procesing and e...ranjithahb ranjithahbhb
 
Translation in Prokaryotes and Eukaryotes
Translation in Prokaryotes and EukaryotesTranslation in Prokaryotes and Eukaryotes
Translation in Prokaryotes and EukaryotesIkram Ullah
 
Transcription
TranscriptionTranscription
Transcriptionenamifat
 
Nuclear export of mRNA
Nuclear export of mRNANuclear export of mRNA
Nuclear export of mRNAADITIBAGDI
 
artificial or synthetic transcription factor for regulation of gene expression
artificial or synthetic transcription factor for regulation of gene expressionartificial or synthetic transcription factor for regulation of gene expression
artificial or synthetic transcription factor for regulation of gene expressionBalaji Rathod
 
Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.
Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.
Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.Study Buddy
 
Transcription in eukaryotes
Transcription in eukaryotesTranscription in eukaryotes
Transcription in eukaryotesSukhjinder Singh
 
Ribosomes- Protein Synthesis
Ribosomes- Protein SynthesisRibosomes- Protein Synthesis
Ribosomes- Protein SynthesisHassan Ahmed Khan
 

La actualidad más candente (18)

Transcription in prokaryotes
Transcription in prokaryotesTranscription in prokaryotes
Transcription in prokaryotes
 
Regulation of gene expression
Regulation of gene expressionRegulation of gene expression
Regulation of gene expression
 
Gene expression & protein synthesis
Gene expression & protein synthesisGene expression & protein synthesis
Gene expression & protein synthesis
 
Introduction to Transcription
Introduction to TranscriptionIntroduction to Transcription
Introduction to Transcription
 
Unit1 lecture
Unit1 lectureUnit1 lecture
Unit1 lecture
 
Post transcriptional modifications
Post transcriptional modificationsPost transcriptional modifications
Post transcriptional modifications
 
transcription activators, repressors, & control RNA splicing, procesing and e...
transcription activators, repressors, & control RNA splicing, procesing and e...transcription activators, repressors, & control RNA splicing, procesing and e...
transcription activators, repressors, & control RNA splicing, procesing and e...
 
Translation in Prokaryotes and Eukaryotes
Translation in Prokaryotes and EukaryotesTranslation in Prokaryotes and Eukaryotes
Translation in Prokaryotes and Eukaryotes
 
Transcription
TranscriptionTranscription
Transcription
 
Nuclear export of mRNA
Nuclear export of mRNANuclear export of mRNA
Nuclear export of mRNA
 
RNA polymerase
RNA polymeraseRNA polymerase
RNA polymerase
 
artificial or synthetic transcription factor for regulation of gene expression
artificial or synthetic transcription factor for regulation of gene expressionartificial or synthetic transcription factor for regulation of gene expression
artificial or synthetic transcription factor for regulation of gene expression
 
Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.
Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.
Transcription in prokaryotes:mRNA,rRNA and tRNA transcription.
 
Transcription
TranscriptionTranscription
Transcription
 
Transcription, mechanism
Transcription, mechanismTranscription, mechanism
Transcription, mechanism
 
Transcription in eukaryotes
Transcription in eukaryotesTranscription in eukaryotes
Transcription in eukaryotes
 
post transcriptional modifications
post transcriptional modificationspost transcriptional modifications
post transcriptional modifications
 
Ribosomes- Protein Synthesis
Ribosomes- Protein SynthesisRibosomes- Protein Synthesis
Ribosomes- Protein Synthesis
 

Destacado

Inborn errors of metabolism
Inborn errors of metabolism Inborn errors of metabolism
Inborn errors of metabolism Aseem Jain
 
Inborn error of metabolism
Inborn error of metabolismInborn error of metabolism
Inborn error of metabolismhodmedicine
 
Inborn error of metabolism
Inborn error of metabolismInborn error of metabolism
Inborn error of metabolismlamiaa Gamal
 
Inborn errors of carbohydrate metabolism
Inborn errors of carbohydrate metabolismInborn errors of carbohydrate metabolism
Inborn errors of carbohydrate metabolismTapeshwar Yadav
 
Presentation on Inborn errors of metabolism
Presentation on Inborn errors of metabolismPresentation on Inborn errors of metabolism
Presentation on Inborn errors of metabolismnutritionistrepublic
 
Inborn errors of metabolism
Inborn errors of metabolismInborn errors of metabolism
Inborn errors of metabolismMohammed Ellulu
 
Lesson 7.1 inborn errors of metabolism
Lesson 7.1 inborn errors of metabolism Lesson 7.1 inborn errors of metabolism
Lesson 7.1 inborn errors of metabolism princesa2000
 

Destacado (8)

Inborn errors of metabolism
Inborn errors of metabolism Inborn errors of metabolism
Inborn errors of metabolism
 
Inborn error of metabolism
Inborn error of metabolismInborn error of metabolism
Inborn error of metabolism
 
Inborn errors of metabolism
Inborn errors of metabolismInborn errors of metabolism
Inborn errors of metabolism
 
Inborn error of metabolism
Inborn error of metabolismInborn error of metabolism
Inborn error of metabolism
 
Inborn errors of carbohydrate metabolism
Inborn errors of carbohydrate metabolismInborn errors of carbohydrate metabolism
Inborn errors of carbohydrate metabolism
 
Presentation on Inborn errors of metabolism
Presentation on Inborn errors of metabolismPresentation on Inborn errors of metabolism
Presentation on Inborn errors of metabolism
 
Inborn errors of metabolism
Inborn errors of metabolismInborn errors of metabolism
Inborn errors of metabolism
 
Lesson 7.1 inborn errors of metabolism
Lesson 7.1 inborn errors of metabolism Lesson 7.1 inborn errors of metabolism
Lesson 7.1 inborn errors of metabolism
 

Similar a Molecular genetics partii 100131193902-phpapp01

Chapter 7 - DNA to Protein.ppt
Chapter 7 - DNA to Protein.pptChapter 7 - DNA to Protein.ppt
Chapter 7 - DNA to Protein.pptahmedisseali
 
DNA Transcription
DNA TranscriptionDNA Transcription
DNA Transcriptionammara12
 
The flow of genetic information transcription
The flow of genetic information transcriptionThe flow of genetic information transcription
The flow of genetic information transcriptionLama K Banna
 
4.3 Transcription and Translation
4.3 Transcription and Translation4.3 Transcription and Translation
4.3 Transcription and TranslationPatricia Lopez
 
RNA Synthesis (Transcription).pptx
RNA Synthesis (Transcription).pptxRNA Synthesis (Transcription).pptx
RNA Synthesis (Transcription).pptxGraceT12
 
Molecular Genetics Part II
Molecular Genetics Part IIMolecular Genetics Part II
Molecular Genetics Part IIJolie Yu
 
Information Flow in Microbes Part 2
Information Flow in Microbes Part 2Information Flow in Microbes Part 2
Information Flow in Microbes Part 2ssuser65d8e1
 
lect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.pptlect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.pptAmosWafula3
 
lect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.pptlect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.pptmuhammedsayfadin
 
Basics of molecular biology tools and techniques
Basics of molecular biology tools and techniquesBasics of molecular biology tools and techniques
Basics of molecular biology tools and techniquesBOTANYWith
 
Basics of molecular biology
Basics of molecular biologyBasics of molecular biology
Basics of molecular biologyMangesh Bhosale
 
Basics of molecular biology
Basics of molecular biologyBasics of molecular biology
Basics of molecular biologyIhteram Ullah
 
Basics of molecular biology
Basics of molecular biologyBasics of molecular biology
Basics of molecular biologyAshfaq Ahmad
 
Unit III (Nucleic acid and genetic code).ppt
Unit III (Nucleic acid and genetic code).pptUnit III (Nucleic acid and genetic code).ppt
Unit III (Nucleic acid and genetic code).pptDrJoginderSingh2
 
104 Genetics and cellular functionLearning Objective.docx
104 Genetics and cellular functionLearning Objective.docx104 Genetics and cellular functionLearning Objective.docx
104 Genetics and cellular functionLearning Objective.docxaulasnilda
 
Basics of Molecular Biology
Basics of Molecular BiologyBasics of Molecular Biology
Basics of Molecular BiologyTapeshwar Yadav
 

Similar a Molecular genetics partii 100131193902-phpapp01 (20)

Chapter 7 - DNA to Protein.ppt
Chapter 7 - DNA to Protein.pptChapter 7 - DNA to Protein.ppt
Chapter 7 - DNA to Protein.ppt
 
Proteins synthesis.ppt
Proteins synthesis.pptProteins synthesis.ppt
Proteins synthesis.ppt
 
DNA Transcription
DNA TranscriptionDNA Transcription
DNA Transcription
 
The flow of genetic information transcription
The flow of genetic information transcriptionThe flow of genetic information transcription
The flow of genetic information transcription
 
4.3 Transcription and Translation
4.3 Transcription and Translation4.3 Transcription and Translation
4.3 Transcription and Translation
 
4.3 Transcription and translation
4.3 Transcription and translation4.3 Transcription and translation
4.3 Transcription and translation
 
RNA Synthesis (Transcription).pptx
RNA Synthesis (Transcription).pptxRNA Synthesis (Transcription).pptx
RNA Synthesis (Transcription).pptx
 
Molecular Genetics Part II
Molecular Genetics Part IIMolecular Genetics Part II
Molecular Genetics Part II
 
Information Flow in Microbes Part 2
Information Flow in Microbes Part 2Information Flow in Microbes Part 2
Information Flow in Microbes Part 2
 
Genetics
GeneticsGenetics
Genetics
 
Transcription
TranscriptionTranscription
Transcription
 
lect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.pptlect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.ppt
 
lect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.pptlect-1-Basics-of-Molecular-Biology.ppt
lect-1-Basics-of-Molecular-Biology.ppt
 
Basics of molecular biology tools and techniques
Basics of molecular biology tools and techniquesBasics of molecular biology tools and techniques
Basics of molecular biology tools and techniques
 
Basics of molecular biology
Basics of molecular biologyBasics of molecular biology
Basics of molecular biology
 
Basics of molecular biology
Basics of molecular biologyBasics of molecular biology
Basics of molecular biology
 
Basics of molecular biology
Basics of molecular biologyBasics of molecular biology
Basics of molecular biology
 
Unit III (Nucleic acid and genetic code).ppt
Unit III (Nucleic acid and genetic code).pptUnit III (Nucleic acid and genetic code).ppt
Unit III (Nucleic acid and genetic code).ppt
 
104 Genetics and cellular functionLearning Objective.docx
104 Genetics and cellular functionLearning Objective.docx104 Genetics and cellular functionLearning Objective.docx
104 Genetics and cellular functionLearning Objective.docx
 
Basics of Molecular Biology
Basics of Molecular BiologyBasics of Molecular Biology
Basics of Molecular Biology
 

Más de Muhammad Fahad Saleh (20)

Chemical coordination
Chemical coordinationChemical coordination
Chemical coordination
 
Nervous coordination
Nervous coordinationNervous coordination
Nervous coordination
 
Cupping therapy
Cupping therapyCupping therapy
Cupping therapy
 
Plant classification
Plant classificationPlant classification
Plant classification
 
Introduction to plants 1233859493415311-3
Introduction to plants 1233859493415311-3Introduction to plants 1233859493415311-3
Introduction to plants 1233859493415311-3
 
Chp9 growth and development
Chp9 growth and developmentChp9 growth and development
Chp9 growth and development
 
Chap. 4 plant reproduction final
Chap. 4 plant reproduction finalChap. 4 plant reproduction final
Chap. 4 plant reproduction final
 
plant morphological lab activities ch 091129203156-phpapp01
plant morphological lab activities ch 091129203156-phpapp01plant morphological lab activities ch 091129203156-phpapp01
plant morphological lab activities ch 091129203156-phpapp01
 
chapter 4
chapter 4chapter 4
chapter 4
 
Stems 100926175806-phpapp02
Stems 100926175806-phpapp02Stems 100926175806-phpapp02
Stems 100926175806-phpapp02
 
Mende
MendeMende
Mende
 
Genotype and phenotype
Genotype and phenotypeGenotype and phenotype
Genotype and phenotype
 
Genetics 2
Genetics 2Genetics 2
Genetics 2
 
Genetics
GeneticsGenetics
Genetics
 
Genetics
GeneticsGenetics
Genetics
 
Genetic code 2081
Genetic code 2081Genetic code 2081
Genetic code 2081
 
Genetic traits
Genetic traitsGenetic traits
Genetic traits
 
52 ch13mendel2007
52 ch13mendel200752 ch13mendel2007
52 ch13mendel2007
 
07 gene mutations
07 gene mutations07 gene mutations
07 gene mutations
 
Zoology kingdom animalia
Zoology kingdom animaliaZoology kingdom animalia
Zoology kingdom animalia
 

Último

CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...Nguyen Thanh Tu Collection
 
How to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using CodeHow to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using CodeCeline George
 
How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17Celine George
 
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptxSandy Millin
 
Department of Health Compounder Question ‍Solution 2022.pdf
Department of Health Compounder Question ‍Solution 2022.pdfDepartment of Health Compounder Question ‍Solution 2022.pdf
Department of Health Compounder Question ‍Solution 2022.pdfMohonDas
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxDr. Asif Anas
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17Celine George
 
Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.raviapr7
 
A gentle introduction to Artificial Intelligence
A gentle introduction to Artificial IntelligenceA gentle introduction to Artificial Intelligence
A gentle introduction to Artificial IntelligenceApostolos Syropoulos
 
How to Solve Singleton Error in the Odoo 17
How to Solve Singleton Error in the  Odoo 17How to Solve Singleton Error in the  Odoo 17
How to Solve Singleton Error in the Odoo 17Celine George
 
Prescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxPrescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxraviapr7
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17Celine George
 
Protein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptxProtein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptxvidhisharma994099
 
3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptx3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptxmary850239
 
How to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesHow to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesCeline George
 
Over the counter (OTC)- Sale, rational use.pptx
Over the counter (OTC)- Sale, rational use.pptxOver the counter (OTC)- Sale, rational use.pptx
Over the counter (OTC)- Sale, rational use.pptxraviapr7
 
CapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptxCapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptxCapitolTechU
 
Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.EnglishCEIPdeSigeiro
 

Último (20)

CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
 
How to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using CodeHow to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using Code
 
How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17
 
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
 
March 2024 Directors Meeting, Division of Student Affairs and Academic Support
March 2024 Directors Meeting, Division of Student Affairs and Academic SupportMarch 2024 Directors Meeting, Division of Student Affairs and Academic Support
March 2024 Directors Meeting, Division of Student Affairs and Academic Support
 
Department of Health Compounder Question ‍Solution 2022.pdf
Department of Health Compounder Question ‍Solution 2022.pdfDepartment of Health Compounder Question ‍Solution 2022.pdf
Department of Health Compounder Question ‍Solution 2022.pdf
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptx
 
Prelims of Kant get Marx 2.0: a general politics quiz
Prelims of Kant get Marx 2.0: a general politics quizPrelims of Kant get Marx 2.0: a general politics quiz
Prelims of Kant get Marx 2.0: a general politics quiz
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17
 
Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.
 
A gentle introduction to Artificial Intelligence
A gentle introduction to Artificial IntelligenceA gentle introduction to Artificial Intelligence
A gentle introduction to Artificial Intelligence
 
How to Solve Singleton Error in the Odoo 17
How to Solve Singleton Error in the  Odoo 17How to Solve Singleton Error in the  Odoo 17
How to Solve Singleton Error in the Odoo 17
 
Prescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxPrescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptx
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17
 
Protein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptxProtein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptx
 
3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptx3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptx
 
How to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesHow to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 Sales
 
Over the counter (OTC)- Sale, rational use.pptx
Over the counter (OTC)- Sale, rational use.pptxOver the counter (OTC)- Sale, rational use.pptx
Over the counter (OTC)- Sale, rational use.pptx
 
CapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptxCapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptx
 
Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.
 

Molecular genetics partii 100131193902-phpapp01

  • 1. Molecular Genetics Part II From Gene to Protein
  • 2. History • Archibald Garrod – 1909 • First to suggest that genes dictate phenotype through production of proteins • Believed that genetic diseases resulted from the inability to make particular enzymes • “Inborn errors of metabolism”
  • 3. One Gene – One Enzyme • Beadle & Ephrussi – 1930’s • Studied mutations affecting eye color in Drosophila • Concluded that each mutation blocks pigment synthesis at a specific step by preventing production of the enzyme that catalyzes that step • Specific pathways were not known, so results were inconclusive
  • 4. Beadle & Tatum • Treated Neurospora (a mold) with X-rays • Looked for mutations in nutritional requirements – Wild type Neurospora grows on minimal medium (agar enriched with a few nutrients) – All mutants will grow on complete medium (agar plus all 20 amino acids & other nutrients) • Identified the specific amino acid required for growth by each mutant – That identified the defective synthetic pathway – Looked at each intermediate step in the blocked synthetic pathway • Concluded that mutation in a single gene blocked production of a single enzyme
  • 6. One Gene – One Polypeptide • Not all proteins are enzymes • Can extend one gene = one enzyme doctrine to one gene = one polypeptide • Many proteins are comprised of two or more polypeptides
  • 7. Central Dogma • How does the sequence of a strand of DNA correspond to the amino acid sequence of a protein? • The central dogma of molecular biology, states that:
  • 8. Transcription & Translation • DNA is first copied (transcribed) to an RNA intermediate • The RNA intermediate is then translated to protein • Why have an intermediate between DNA and the proteins it encodes?
  • 9. Why RNA? • The DNA remains protected in the nucleus, away from caustic enzymes in the cytoplasm. • Gene information can be amplified – Many copies of an RNA can be made from one copy of DNA. • Greater regulation of gene expression – Specific controls can act at each step in the pathway between DNA and proteins. – The more elements there are in the pathway, the more opportunities there are for control
  • 10. What is RNA? • RNA has the same primary structure as DNA – consists of a sugar-phosphate backbone, with nucleotides attached to the 1' C of the sugar. • Differences between DNA and RNA : – Contains the sugar ribose instead of deoxyribose – The nucleotide, uracil, is substituted for thymine – RNA exists as a single-stranded molecule. • Because of the extra hydroxyl group on the sugar, RNA is too bulky to form a a stable double helix. • Regions of double helix can form where there is some base pair complementation resulting in hairpin loops.
  • 11. Types of RNA • mRNA - messenger RNA – A copy of a gene. – Has a sequence complementary to one strand of the DNA & identical to the other strand. – Carries the information stored in DNA in the nucleus to the ribosomes in the cytoplasm where protein is made. • tRNA - transfer RNA – A small RNA with a very specific structure that can bind an amino acid at one end, and mRNA at the other end. – Acts as an ‘adaptor’ to carry & attach amino acids to the appropriate place on the mRNA.
  • 12. Types of RNA (Cont.) • rRNA - ribosomal RNA – One of the structural components of the ribosome. – Has a sequence complimentary to regions of the mRNA – Allows ribosome to bind to an mRNA • snRNA - small nuclear RNA – Is involved in the machinery that processes RNA's as they travel between the nucleus and the cytoplasm.
  • 13. The Genetic Code • How does mRNA specify an amino acid sequence? • It would be impossible for each amino acid to be specified by one nucleotide – there are only 4 nucleotides and 20 amino acids. – two nucleotide combinations could only specify 16 amino acids. • Each amino acid is specified by a combination of three nucleotides, called a codon
  • 16. The Code is Redundant, Not Ambiguous • Each amino acid may be specified by up to six codons – In many cases, codons that are synonyms differ only in the third base of the triplet • Different organisms have different frequencies of codon usage. – A giraffe might use CGC for arginine much more often than CGA, and the reverse might be true for a sperm whale. • Some codons specify “stop” (or “start) • There is no ambiguity – the same codon ALWAYS codes for the same amino acid
  • 17. Codons & Anticodons • How do tRNAs recognize to which codon to bring an amino acid? • The tRNA has an anticodon on its mRNA- binding end • The anticodon is complementary to the codon on the mRNA. • Each tRNA only binds the appropriate amino acid for its anticodon
  • 19. Transcription • How does the sequence information from DNA get transferred to mRNA? • How is this information carried to the ribosomes in the cytoplasm? • This process is called transcription • Highly similar to DNA replication. • Different enzymes are used in transcription. • The most important is RNA polymerase
  • 20. RNA Polymerase • RNA polymerase is a holoenzyme – an agglomeration of many different factors • Together, direct the synthesis of mRNA • Pries the DNA strands apart • Strings complimentary RNA nucleotides on the DNA template • Like DNA polymerase, can only add to the 3’ end • So only one mRNA is made, elongating 5’  3’
  • 21. Stages of Transcription • Initiation • Elongation • Termination
  • 23. Initiation • RNA polymerase must recognize the beginning of a gene to know where to start synthesizing mRNA. • One part of the enzyme has a high affinity for a particular DNA sequence that appears at the beginning of genes. • The sequence where RNA polymerase attaches to the DNA and begins transcription = the promoter – a unidirectional sequence on one strand of the DNA • Tells RNA polymerase both where to start and in which direction (that is, on which strand) to continue synthesis.
  • 24. The Promoter • In prokaryotes, RNA polymerase recognizes and binds the promoter • The bacterial promoter almost always contains some version of the following elements:
  • 25. Eukaryotic Promoters • In eukaryotes special proteins, transcription factors, mediate binding RNA polymerase and the promoter • RNA polymerase binds to the promoter only after transcription factors bind • Transcription factors + RNA polymerase, bound to the promoter = transcription initiation complex • Eukaryotic promoters usually include a TATA box – A nucleotide sequence containing TATA about 25 nucleotides prior to the start point
  • 27. Elongation • The RNA polymerase stretches open the double helix at the start point in the DNA and begins synthesis of a complementary RNA strand on one of the DNA strands • The RNA polymerase recruits RNA nucleotides in the same way that DNA polymerase recruits dNTPs. • Since synthesis only proceeds in the 5' to 3' direction, there is no need for Okazaki fragments.
  • 29. Sense & Antisense • Synthesis only occurs in the 5’ to 3’ direction • In transcription, only one DNA strand is copied • We call the strand that is copied the antisense or template strand • The other strand, which is identical to the mRNA made (substituting U for T), is the sense or coding strand.
  • 30. Termination of Transcription • How does RNA polymerase know when to stop transcribing a gene? • Sequence that signals the end of transcription = terminator • RNA polymerase transcribes the terminator – The transcribed terminator actually ends the process • In prokaryotes there is no nucleus, so ribosomes can begin making protein from an mRNA immediately • The terminator sequence of the mRNA allows it to form a hairpin loop, which blocks the ribosome. – The ribosome falls off the mRNA, – That signals termination by the RNA polymerase. – RNA polymerase falls off the DNA and transcription
  • 31. Eukaryotic Termination • RNA polymerase continues for hundreds of nucleotides beyond the termination signal • AAUAAA • At a point 10 to 35 nucleotides past the AAUAAA, the forming m-RNA is cut free • The cleavage site is the point of addition of a poly-A tail
  • 32. Post Transcription Modification • In eukaryotes, enzymes modify pre-mRNA before it is sent to the cytoplasm • Both ends of the transcript are altered • The 5’ end is capped with modified guanine – Protects mRNA from degradation – Helps attach the ribosome • At the 3’ end an enzyme makes a poly-A tail formed from 50 to 250 adenine nucleotides – Inhibits degradation and helps ribosome attach – May also help export mRNA out of the nucleus • Interior sections are cut out, and the remaining parts are spliced together
  • 34. Introns & Exons • Most eukaryotic genes and their RNA transcripts have long noncoding stretches of nucleotides = introns • Noncoding sequences are interspersed between coding sections • Coding sections = exons • That is, the sequence of eukaryotic DNA that codes for a polypeptide is not continuous • RNA polymerase transcribes both introns and exons
  • 35. RNA Splicing • Introns are cut out and exons are spliced together before mRNA exits the nucleus • Short nucleotide sequences at the end of introns are signals for RNA splicing • Small nuclear ribonucleoproteins (snRNPs) recognize splice sites – Composed of snRNA & protein • Several snRNPs and additional proteins form a complex = spliceosome • At splice sites at the end of an intron, cuts out the intron and fuses the exons
  • 37. Why Introns? • Introns may play regulatory role in the cell • Split genes allow a single gene to code more than one kind of polypeptide • Outcome depends on which sections are treated as exons during RNA processing – Alternative RNA splicing • May facilitate evolution of new proteins • Increase possibility of potentially beneficial crossing-over of genes
  • 39. Translation • How do messenger RNAs direct protein synthesis? • The message encoded in the mRNA is an amino acid sequence • mRNA travels to ribosome in the cytoplasm, where the message is read • The specified amino acids are assembled on the mRNA template on the ribosome • Enzymes help form the sequenced amino acids into a polypeptide
  • 41. The Ribosome • The cellular factory where proteins are synthesized • Consists of structural RNA and ~ 80 different proteins. • In its inactive state, it exists as two subunits – a large subunit and a small subunit. • When the small subunit encounters an mRNA, it begins translation of the mRNA to protein. • There are three sites in the large subunit – The A site accepts a new tRNA bearing an amino acid – the P site bears the tRNA attached to the growing chain. – The E site contains the exiting tRNA
  • 43. Charging the tRNA • tRNA (transfer RNA) acts as a translator between mRNA and protein • Each tRNA has a specific anticodon and an amino acid acceptor site. • Each tRNA also has a specific charger protein; – This protein can only bind to that particular tRNA and attach the correct amino acid to the acceptor site. – These charger proteins are called aminoacyl tRNA synthetases • The energy to make this bond comes from ATP.
  • 45. Aminoacyl-tRNA Synthases • Each tRNA must match with the correct amino acid – Each tRNA must attach only the amino acid specified by the mRNA codon to which the tRNA anticodon binds • The amino acid is joined to the tRNA by an aminoacyl-tRNA synthase – There are 20 of these enzymes; one for each amino acid • Catalyzes the covalent bond between the amino acid and tRNA • The active site of each aminoacyl-tRNA synthase fits only a specific amino acid and tRNA • Once the amino acid is bound, the tRNA is aminoacyl tRNA
  • 47. Wobble • If there was one tRNA for each mRNA codon, there would be 61 different tRNAs • Actually, there are fewer • Some tRNAs have anticodons that recognize 2 or more different codons • Base pairing rules between the third base of a codon and its tRNA anticodon are not a rigid as DNA to mRNA pairing – Example: U in tRNA can pair with either A or T in the third position of an mRNA codon • This flexibility is called wobble
  • 49. Initiation of Translation • The start signal for translation is the codon ATG – Codes for methionine. – Not every protein starts with methionine, – Often this first amino acid will be removed in post-translational processing. • A tRNA charged with methionine binds to the translation start signal. • The large subunit binds to the mRNA and the small subunit • Elongation begins.
  • 51. Elongation of the New Protein • After the first charged tRNA appears in the A site, the ribosome shifts so that the tRNA is in the P site. • New charged tRNAs, corresponding the codons of the mRNA, enter the A site, and a peptide bond is formed between the two amino acids. • The first tRNA is now released • The ribosome shifts again so that a tRNA carrying two amino acids is now in the P site • A new charged tRNA can bind to the A site. • This process of elongation continues until the ribosome reaches a stop codon.
  • 53. Termination of the Protein • When the ribosome reaches a stop codon, no aminoacyl tRNA binds to the empty A site. • This is the ribosome’s signal to break into its large and small subunits, • Releasing the new protein and the mRNA.
  • 55. Polyribosomes • A single mRNA can be used to make many copies of a polypeptide at the same time • Multiple ribosomes can read the same mRNA strand, like beads on a string • These strings are called polyribosomes
  • 57. Post-Translational Processing • This isn't always the end of the story for the new protein. • Often it will undergo post-translational modifications. • Modifications include: • Cleavage by a proteolytic (protein-cutting) enzyme at a specific place. • Having some amino acids altered. – For example, a tyrosine residue might be phosphorylated. • Become glycosylated. – Many proteins have carbohydrates covalently attached to asparagine residues.
  • 59. Mutations • What kinds of errors can occur in DNA? • What causes them? • What are their effects? • Types of mutations: – Chromosomal mutations – Point mutations – Frameshift mutations
  • 61. Chromosomal Mutations • Mutations that occur at a macroscopic level. • Large sections of chromosomes can be altered or shifted, leading to changes in the way genes are expressed. • Types of chromosomal mutations: – Translocations – Inversions – Deletions – Nondisjunction
  • 62. Translocations & Inversions • Translocation – The interchange of large segments of DNA between two chromosomes. – Can change gene expression if a gene is at the translocation breakpoint or if it is reattached so that it is incorrectly regulated • Inversion – Occurs when a region of DNA flips its orientation with respect to the rest of the chromosome. – Rotates, end for end – This can lead to the same problems as translocations.
  • 63. Deletions & Nondisjunction • Deletion – Sometimes large regions of a chromosome are deleted. – This can lead to a loss of important genes. • Nondisjunction – Sometimes chromosomes do not divide correctly in cell division – When large regions of a chromosome are altered (such as translocation), the chromosome may not segregate properly during cell division – One daughter cell will end up with extra genetic material, one will end up with less than its share – This is called nondisjunction. – When there are extra or too few copies of a gene, the cell will have problems
  • 64. Point Mutations • Point mutations are single base pair changes. • Three possible outcomes: • Nonsense mutation – Creates a stop codon where none previously existed. – This shortens the resulting protein, possibly removing essential regions. • Missense mutation – Changes the code of the mRNA. – Which changes the resulting amino acid – This may alter the shape and properties of the protein. • Silent mutation – Has no effect on protein sequence. – Because the genetic code is redundant, some changes have no effect
  • 66. Frameshift Mutations • Insertions or deletions have a disastrous effect • mRNA is “read” as a series of three letter words • Insertions or deletions that are not multiples of three, shift the reading frame
  • 67. Frameshift Example • Given the coding sequence: AGA UCG ACG UUA AGC • corresponding to the protein: arginine - serine - threonine - leucine - serine • The insertion of a C-G base pair between bases 6 and 7 would result in the following new code: AGA UCG CAC GUU AAG C • which would result in a non-functional protein: arginine - serine - histidine - valine - lysine • Every amino acid after the insertion will be wrong. • The frame shift might even generate a stop codon which would prematurely end the protein.
  • 69. DNA Repair • If replication of DNA proceeded as was described previously, DNA polymerase would make a mistake on average about every 1000 base pairs. • This level would be unacceptable, because too many genes would be rendered non-functional. • Organisms have elaborate DNA proofreading and repair mechanisms, which can recognize false base-pairing and DNA damage, and repair it. • The actual error rate is more in the region of one in a million to one in a billion.
  • 70. The Beauty of Mutations • Why mutations? • Our environment constantly changes, the Earth and its ecosystems change. • Populations must change to survive • Evolutionary change requires variation, the raw material on which natural selection works • One mechanism for variation and change is at the DNA level. • Mutations can be beneficial and enable the organism to adapt to a changing environment. • However, most mutations are deleterious, and cause varied genetic diseases