Chapter 12 Molecular Genetics

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Chapter 12 Chapter 12 Molecular GeneticsMolecular Genetics12.1 DNA: The Genetic Material12.1 DNA: The Genetic Material

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Discovery of the Genetic Discovery of the Genetic MaterialMaterial

Chromosomes are about 50% nucleic acid and 50% protein, which is the genetic material?

Most scientists thought that protein was the genetic material because protein is more complex

Griffith performed the first major experiment that led to the discovery of DNA as the genetic material

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Significance of Griffith’s work (1928)Significance of Griffith’s work (1928) One strain of bacteria transformed into One strain of bacteria transformed into

another strainanother strain Did not identify what the transforming Did not identify what the transforming

substance wassubstance was

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1944 Oswald Avery identified that DNA 1944 Oswald Avery identified that DNA was the transforming substance in was the transforming substance in Griffith’s experimentsGriffith’s experiments

Most leading scientists did not believe Most leading scientists did not believe himhim

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1952 Hershey and 1952 Hershey and Chase used Chase used radioactively labeled radioactively labeled DNA and DNA and radioactively labeled radioactively labeled protein and proved protein and proved that DNA is the that DNA is the genetic materialgenetic material

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DNA StructureDNA Structure

DNA is made of DNA is made of subunits called subunits called nucleotidesnucleotides

Three parts to a DNA Three parts to a DNA nucleotidenucleotide SugarSugar Phosphate Phosphate Nitrogen BaseNitrogen Base

NUCLEOTIDE

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DNA StructureDNA Structure

Four Different Four Different Nitrogen BasesNitrogen Bases Purine (two rings)Purine (two rings)

AdenineAdenine GuanineGuanine

Pyrimidine (one ring)Pyrimidine (one ring) Cytosine Cytosine ThymineThymine Uracil (not found in Uracil (not found in

DNA)DNA)

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DNA Structure Chargaff’s DNA Structure Chargaff’s RuleRule

Chargaff determined Chargaff determined in 1950 that the in 1950 that the amount of adenine amount of adenine equals the amount of equals the amount of thymine and the thymine and the amount of guanine amount of guanine equals the amount of equals the amount of cytosinecytosine

Chargaff’s Rule: A=T Chargaff’s Rule: A=T and C=Gand C=G

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DNA Structure: X Ray DNA Structure: X Ray DiffractionDiffraction

Rosalind Franklin’s Rosalind Franklin’s (1951) famous photo (1951) famous photo of X ray diffraction of of X ray diffraction of DNADNA

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DNA Structure: Double DNA Structure: Double HelixHelix

IN 1953 Watson and IN 1953 Watson and Crick astounded the Crick astounded the scientific community scientific community with their with their announcement of announcement of DNA’s structureDNA’s structure

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Watson and Crick, Watson and Crick, using Franklin’s using Franklin’s photo, determined photo, determined that DNA is a double that DNA is a double helix with:helix with: Outside strands of Outside strands of

alternating sugar and alternating sugar and phosphatephosphate

C bonds with G with C bonds with G with three hydrogen bondsthree hydrogen bonds

A bonds with T with A bonds with T with two hydrogen bondstwo hydrogen bonds

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DNA called a twisted DNA called a twisted ladderladder

Sugar is deoxyribose Sugar is deoxyribose in the upright rails of in the upright rails of the “ladder” the “ladder” alternating with alternating with phosphate (spacers)phosphate (spacers)

Rungs of the “ladder” Rungs of the “ladder” have a purine base have a purine base H-bonded to a H-bonded to a pyrimidine basepyrimidine base

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DNA strands are DNA strands are antiparellel (one antiparellel (one strand right side up strand right side up and other stand and other stand upside down)upside down)

Stands named by Stands named by their Carbon their Carbon orientation, C-5 (5’) orientation, C-5 (5’) or C-3 (3’)or C-3 (3’)

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Chromosome StructureChromosome Structure

An average sized An average sized chromosome would chromosome would be 5 cm long if the be 5 cm long if the DNA were stretched DNA were stretched outout

DNA is packaged to DNA is packaged to be condensed in the be condensed in the cell’s nucluescell’s nuclues

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Chapter 12 Chapter 12 Molecular GeneticsMolecular Genetics12.2 Replication of DNA12.2 Replication of DNA

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Semiconservative Semiconservative ReplicationReplication

DNA original strand DNA original strand untwists untwists

New base pairs bond New base pairs bond to open existing to open existing strands following strands following base paring rules base paring rules (A=T, C=G)(A=T, C=G)

New strands twist; New strands twist; each new helix is half each new helix is half new half original new half original

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Enzymes Control DNA Enzymes Control DNA ReplicationReplication

Untwisting by DNA Untwisting by DNA helicasehelicase

Strands kept apart by Strands kept apart by single-stranded binding single-stranded binding proteinsproteins

Add “starter” RNA Add “starter” RNA segment by segment by RNA RNA primaseprimase

Add new nucleotides by Add new nucleotides by DNA polymeraseDNA polymerase

This is only the This is only the highlights; there are highlights; there are many other enzymes many other enzymes involvedinvolved

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DNA ReplicationDNA Replication

Because DNA is antiparallel and new Because DNA is antiparallel and new nucleotides can only be added to the 3’ end, nucleotides can only be added to the 3’ end, each strand replicates slightly differentlyeach strand replicates slightly differently

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DNA ReplicationDNA Replication Leading strand replicates by continuous addition of Leading strand replicates by continuous addition of

nucleotides to the 3’ endnucleotides to the 3’ end Lagging strand replicates by producing short DNA Lagging strand replicates by producing short DNA

sections called Okazaki fragmentssections called Okazaki fragments Enzyme Enzyme ligaseligase “glues” the fragments together “glues” the fragments together

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Comparing DNA Replication Comparing DNA Replication in Eukaryotes and in Eukaryotes and ProkaryotesProkaryotes

Eukaryotes have Eukaryotes have multiple areas of DNA multiple areas of DNA replication along one replication along one chromosome chromosome

Prokaryotes have one Prokaryotes have one circular chromosome circular chromosome and have only one and have only one origin of replicationorigin of replication

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Chapter 12 Chapter 12 Molecular GeneticsMolecular Genetics12.3 DNA, RNA, and Protein12.3 DNA, RNA, and Protein

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Central DogmaCentral Dogma

How does the How does the information in DNA, information in DNA, located in the located in the nucleus, allow for the nucleus, allow for the production proteins production proteins in the cytoplasm?in the cytoplasm?

RNA is another form RNA is another form of nucleic acid that of nucleic acid that relays the relays the information.information.

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RNA versus DNARNA versus DNA

RNARNA Single helixSingle helix Ribose sugarRibose sugar Bases: adenine, Bases: adenine,

guanine, cytosine, guanine, cytosine, and uraciland uracil

Several types of RNASeveral types of RNA

DNADNA Double helixDouble helix Deoxyribose sugarDeoxyribose sugar Bases: adenine, Bases: adenine,

guanine, cytosine, guanine, cytosine, and thymineand thymine

One type of DNAOne type of DNA

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RNA versus DNARNA versus DNA

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Types of RNATypes of RNA

Messenger RNA (mRNA): long strands Messenger RNA (mRNA): long strands (hundreds of nucleotides) that are formed (hundreds of nucleotides) that are formed complementary to DNA; leave the nucleus to complementary to DNA; leave the nucleus to carry information to the cytoplasmcarry information to the cytoplasm

Transfer RNA (tRNA): short (80-100 Transfer RNA (tRNA): short (80-100 nucleotides) T-shaped RNA that transport nucleotides) T-shaped RNA that transport amino acidsamino acids

Ribosomal RNA (rRNA): along with protein Ribosomal RNA (rRNA): along with protein make up the ribosomesmake up the ribosomes

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Types of RNATypes of RNA

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DNA to RNA to ProteinDNA to RNA to Protein

Two step process: transcription and Two step process: transcription and translationtranslation

Transcription (rewrite): RNA is made Transcription (rewrite): RNA is made from DNA; occurs in the nucleus from DNA; occurs in the nucleus

Translation (change language): protein is Translation (change language): protein is made from RNA code; occurs in the made from RNA code; occurs in the cytoplasm at the ribosomecytoplasm at the ribosome

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TranscriptionTranscription

A section DNA (ave. size A section DNA (ave. size 8000 nucleotides) in the 8000 nucleotides) in the nucleus untwists and nucleus untwists and unzips. unzips.

RNA nucleotides, RNA nucleotides, following base pairing following base pairing rules, bond on the rules, bond on the leading strand of DNAleading strand of DNA

Like DNA replication Like DNA replication controlled by many controlled by many enzymesenzymes

Occurs in the nucleus

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RNA ProcessingRNA Processing

RNA when it is RNA when it is transcribed must be transcribed must be processedprocessed GTP cap is added to 5’ GTP cap is added to 5’

end to protect and give end to protect and give attach signal to ribosomeattach signal to ribosome

Introns (intervening Introns (intervening sequences) are cut outsequences) are cut out

Exons (expressed Exons (expressed sequences) are put sequences) are put togethertogether

Poly-A tail (30-200 A Poly-A tail (30-200 A nucleotides) added to 3’ nucleotides) added to 3’ end to protect and “get out end to protect and “get out of nucleus” signalof nucleus” signal

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Translation: Making Translation: Making ProteinProtein

Starts when mRNA, Starts when mRNA, tRNA carrying amino tRNA carrying amino acids, and small and acids, and small and large ribosomal large ribosomal subunits come subunits come togethertogether

Concludes when a Concludes when a polypeptide chain in polypeptide chain in producedproduced

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The CodeThe Code

There are 20 amino acids, each is coded There are 20 amino acids, each is coded for by a sequence of 3 nucleotides called for by a sequence of 3 nucleotides called a a codoncodon. .

Discovered during the 1960’s.Discovered during the 1960’s.

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The CodeThe Code

mRNA has the codonmRNA has the codon tRNA has the anticodon tRNA has the anticodon

(complementary to the codon)(complementary to the codon) Example: mRNA codon AUG Example: mRNA codon AUG

would code for the amino acid would code for the amino acid methionine which is also the methionine which is also the start codon start codon

Redundancy exists: more that Redundancy exists: more that one codon per amino acid one codon per amino acid (UAU and UAC codes for (UAU and UAC codes for tyrosine)tyrosine)

Ambiguity does not exist: Ambiguity does not exist: UAU only codes for tyrosine UAU only codes for tyrosine not any other amino acid.not any other amino acid.

mRNA Genetic Code

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TranslationTranslation

1.1. All the players come togetherAll the players come together2.2. First tRNA with anticodon UAC carrying methionine First tRNA with anticodon UAC carrying methionine

bonds with mRNA codon AUG at the P-site of the bonds with mRNA codon AUG at the P-site of the ribosomeribosome

3.3. Second tRNA with anticodon carrying another amino Second tRNA with anticodon carrying another amino acid bonds with complementary mRNA codon at A-acid bonds with complementary mRNA codon at A-site of ribosomesite of ribosome

4.4. Polypeptide bond forms between two amino acidsPolypeptide bond forms between two amino acids5.5. Ribosome moves down the mRNA so that the first Ribosome moves down the mRNA so that the first

tRNA is now in E-site of ribosome (and is released)tRNA is now in E-site of ribosome (and is released)6.6. A-site is now empty to attach the third tRNA carrying A-site is now empty to attach the third tRNA carrying

the third amino acidthe third amino acid7.7. Steps 4-7 repeated until mRNA codon for stop is Steps 4-7 repeated until mRNA codon for stop is

signaled, then polypeptide chain releasedsignaled, then polypeptide chain released

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One Gene-One EnzymeOne Gene-One Enzyme

The Beadle and The Beadle and Tatum experiment Tatum experiment showed that one showed that one gene codes for gene codes for one enzyme. We one enzyme. We now know that one now know that one gene codes for gene codes for one polypeptide.one polypeptide.

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Chapter 12 Chapter 12 Molecular GeneticsMolecular Genetics12.4 Gene Regulation and Mutation12.4 Gene Regulation and Mutation

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Prokaryote Gene Prokaryote Gene RegulationRegulation

Ability of an organism to control which Ability of an organism to control which genes are transcribed in response to the genes are transcribed in response to the environmentenvironment

An An operonoperon is a section of DNA that is a section of DNA that contains the genes for the proteins contains the genes for the proteins needed for a specific metabolic pathway.needed for a specific metabolic pathway.

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LacLac Operon Operon

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TryTry Operon Operon

What would an off Try operon look like?

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Eukaryote Gene Eukaryote Gene RegulationRegulation

Controlling transcription: transcription factors Controlling transcription: transcription factors ensure that a gene is used at the right time and ensure that a gene is used at the right time and that proteins are made in the right amounts that proteins are made in the right amounts Promoters: stabilize binding of RNA polymerasePromoters: stabilize binding of RNA polymerase Regulatory proteins: control rate of transcriptionRegulatory proteins: control rate of transcription

The complex structure of eukaryotic DNA also The complex structure of eukaryotic DNA also regulates transcription.regulates transcription.

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Hox genes are Hox genes are responsible for the responsible for the general body pattern general body pattern of most animals.of most animals.

Hox genes code for Hox genes code for transcription factors transcription factors that are active in that are active in zones of the embryo zones of the embryo that are in the same that are in the same order as the genes order as the genes on the chromosomeon the chromosome

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RNA interference can stop the mRNA RNA interference can stop the mRNA from translating its message.from translating its message.

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MutationsMutations

Mistakes occur in copying the DNA during Mistakes occur in copying the DNA during replication.replication.

Mechanisms exist for correcting these mistakesMechanisms exist for correcting these mistakes If the mistakes are permanent then a mutation If the mistakes are permanent then a mutation

occursoccurs If a mutation in the DNA occurs, then the If a mutation in the DNA occurs, then the

protein that is made from this DNA instruction protein that is made from this DNA instruction can be absent or nonfunctional.can be absent or nonfunctional.

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MutationsMutations

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MutationsMutations

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Types of MutationsTypes of Mutations

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Chromosomal MutationsChromosomal Mutations

Pieces of Pieces of chromosomes get chromosomes get deleted, duplicated, deleted, duplicated, inverted, inserted or inverted, inserted or translocatedtranslocated

Visible on karyotypeVisible on karyotype

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Chromosomal MutationsChromosomal Mutations

Fragile X Fragile X chromosome is due chromosome is due about 30 extra about 30 extra repeated CGG repeated CGG codons near the tip codons near the tip of the X chromosomeof the X chromosome

Results in many Results in many mental and mental and behavioral symptomsbehavioral symptoms

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Protein Folding and Protein Folding and StabilityStability

Incorrect amino acid sequences can lead Incorrect amino acid sequences can lead to changes in the shape and thus the to changes in the shape and thus the function of proteinsfunction of proteins

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Causes of MutationsCauses of Mutations

Mutagens are agents that cause Mutagens are agents that cause mutationsmutations

Spontaneous: no know cause; wrong Spontaneous: no know cause; wrong nucleotide nucleotide Happens 1/100,000 base pairsHappens 1/100,000 base pairs Goes unfixed less than one in one billionGoes unfixed less than one in one billion

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Causes of MutationsCauses of Mutations

Chemicals like asbestos, benzene, Chemicals like asbestos, benzene, formaldehyde, many agents in cigarette formaldehyde, many agents in cigarette smoke, and many otherssmoke, and many others

Affect DNA by changing chemical nature Affect DNA by changing chemical nature of the basesof the bases

May resemble nucleotides and bond in May resemble nucleotides and bond in place of the DNA nucleotides preventing place of the DNA nucleotides preventing DNA replicationDNA replication

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Causes of MutationsCauses of Mutations Radiation: high energy Radiation: high energy

rays like X rays and rays like X rays and gamma rays; form free gamma rays; form free radicals (charged radicals (charged escaped electrons) that escaped electrons) that damages DNAdamages DNA

UV radiation can cause UV radiation can cause adjacent thymines to adjacent thymines to bind with each other bind with each other instead of instead of complementary complementary nucleotides causing a nucleotides causing a “kink” in the DNA “kink” in the DNA molecule which prevents molecule which prevents replicationreplication

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Molecular Genetics

Somatic cell mutations are not Somatic cell mutations are not passed on to the next generation.passed on to the next generation.

Mutations that occur in sex cells are Mutations that occur in sex cells are passed on to the organism’s offspring passed on to the organism’s offspring and will be present in every cell of the and will be present in every cell of the offspring.offspring.

Body Cell versus Sex Cell Body Cell versus Sex Cell MutationMutation

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Chapter 12 Molecular Genetics