GeneticsGenetics

AP BiologyAP Biology

The Discovery of DNA The Discovery of DNA StructureStructure

Rosalind Franklin: x-ray diffraction Rosalind Franklin: x-ray diffraction photographs of DNAphotographs of DNA

Watson & Crick built model based Watson & Crick built model based on x-ray diffraction photoson x-ray diffraction photos

DNA StructureDNA Structure

Deoxyribose sugar backbone, Deoxyribose sugar backbone, alternating with phosphate groupsalternating with phosphate groups

Nitrogenous bases held together by Nitrogenous bases held together by hydrogen bonds: Adenine, Thymine, hydrogen bonds: Adenine, Thymine, Cytosine and GuanineCytosine and Guanine

Arranged in a double helixArranged in a double helix Chargaff’s base pairing rules: A-T; G-Chargaff’s base pairing rules: A-T; G-

CC

Anti-parallel nature of Anti-parallel nature of DNADNA

5’ 3’

3’ 5’

DNA ReplicationDNA Replication Makes an exact copy Double helix separates at Origins of Origins of

ReplicationReplication Each strand serves as the template

for a new strand Semi-conservative replicationSemi-conservative replication

DNA polymerase builds new strand 5’ to 3’ (adds nucleotides onto 3’ end (OH)

DNA replication occurs in a 5’ to 3’ direction: Leading strand

Other side is constructed in 5’ to 3’ fragments called Okasaki fragmentsOkasaki fragments : Lagging strand

From Gene to Protein:From Gene to Protein:DNA contains information of amino acid sequence in proteins

TranscriptionTranscriptionSynthesis of RNA using the DNA as a template: contains gene’s protein building instructionsRNA Structure:

Contains ribose sugar, Base thymine is replaced with uracil, single stranded

Types of RNA:

Ribosomal RNA (rRNA) – manufactured in nucleolus

Transfer RNA (tRNA)

Messenger RNA (mRNA)

Single stranded RNA molecules fold into secondary structures

Characteristic secondary structure of tRNA

Uracil

RNA EditingRNA Editing

RNA molecule made by transcription RNA molecule made by transcription – premRNA– premRNA

Contains stretches of bases – Contains stretches of bases – ““intronsintrons” that do not code for ” that do not code for proteinsproteins

Introns are removed and coding Introns are removed and coding sequences “sequences “exonsexons” are spliced ” are spliced togethertogether

Role of RNA SplicingRole of RNA Splicing

““One gene, One polypeptide” One gene, One polypeptide” hypothesis: a gene of DNA codes for hypothesis: a gene of DNA codes for one protein.one protein.

Several proteins can be Several proteins can be manufactured from a single gene manufactured from a single gene due to due to alternative splicingalternative splicing

TranslationTranslationtRNAs bring amino acids to the ribosome to assemble proteins

Translation – the Translation – the specificsspecifics

Amino acids joined to tRNAs by a Amino acids joined to tRNAs by a specific specific

aminoacyl-tRNA synthetaseaminoacyl-tRNA synthetase Ribosomal Structure: Ribosomal Structure:

P site – holds tRNA carrying amino acid the P site – holds tRNA carrying amino acid the growing polypetide chaingrowing polypetide chain

A site – holds the tRNA carrying the next A site – holds the tRNA carrying the next amino acid to be added to the chainamino acid to be added to the chain

E site – discharged tRNAs leave through E site – discharged tRNAs leave through this sitethis site

Translation – the specifics Translation – the specifics continuedcontinued

Initiation: mRNA, initiator tRNA, ribosomal : mRNA, initiator tRNA, ribosomal subunits assemble. Initiator tRNA sits in P site subunits assemble. Initiator tRNA sits in P site and A site is vacantand A site is vacant

Elongation:Elongation: Codon recognition: H bonding between tRNA and

codon in A site. Requires elongation factors & GTP Peptide bond formation: an rRNA molecule

catalyzes formation of peptide bond growing chain from P site to the new amino acid in the A site

Translocation: the tRNA in the A site (now has polypetide chain) moves to P site. Blank tRNA in P site moved to E site.

Termination: stop codon – release factor binds to A site & causes the addition of water – hydrolyzes tRNA from protein chain.

DNA Mutations - Effects on DNA Mutations - Effects on TranslationTranslation

Point mutationsPoint mutations Insertions and DeletionsInsertions and Deletions

Frameshift mutationsFrameshift mutations Base pair substitutionBase pair substitution

Missense – still codes for amino acidMissense – still codes for amino acid Nonsense – prematurely codes for a stop Nonsense – prematurely codes for a stop

codoncodon

Control of Transcription in Control of Transcription in Eukarytoic cellsEukarytoic cells

Transcription is most often the result of a Transcription is most often the result of a chemical signal chemical signal Some genes are Some genes are constitutively activeconstitutively active – –

meaning they are always turned on in a cellmeaning they are always turned on in a cell Chemical signals often in the form of Chemical signals often in the form of

hormones – either steroidal or peptidehormones – either steroidal or peptide Peptide hormones cannot diffuse into the cell Peptide hormones cannot diffuse into the cell

and bind hormone receptors on the cell and bind hormone receptors on the cell membranemembrane

Steroid hormones are able to diffuse easily Steroid hormones are able to diffuse easily into the nucleus where they bind steroid into the nucleus where they bind steroid hormone hormone receptors receptors that function as that function as transcription factorstranscription factors (transcription factors (transcription factors “turn on/off” the transcription of a gene“turn on/off” the transcription of a gene

Peptide hormonesPeptide hormonesBinding of

peptide hormone to

cell membrane receptor

Activation of cellular

signaling molecules that carry signal to

the nucleusChange in

transcription of a gene

Examples of peptide hormones: insulin, adrenaline, vasopressin, etc.

Steroid hormone Steroid hormone signalingsignaling

Examples of steroid hormones: estrogen, testosterone, glucocorticoids

Intronic RNAIntronic RNA

Once thought to be completely Once thought to be completely nonfunctionalnonfunctional

Within the last 5-7 years: microRNAsWithin the last 5-7 years: microRNAs Now found that microRNAs can bind Now found that microRNAs can bind

to newly transcribed mRNA and to newly transcribed mRNA and target them for degradationtarget them for degradation

Another way that the cell controls Another way that the cell controls what proteins are madewhat proteins are made

Can be synthesized in the laboratory and can be used to shut down production of a protein – possible therapeutic uses