DNAIt’s not just for college anymore!

Web Sites

• DNA structure and replication animation

• Overview of gene expression

• DNA Models & Translation model

http://207.207.4.198/pub/flash/24/menu.swf

http://www.genomicseducation.ca/animations/gene_expression.asp

http://www.indigo.com/models/dna-models.html

Learning Goals for DNA & Genetics

• Know structure/function of DNA• Know DNA is genetic material• Illustrate how DNA specifies traits• Understand mutations are change in DNA

sequence• Understand relationship between

mutations in DNA and expressed phenotype

What Is DNA

• Deoxyribonucleic acid– Everyone knows this?

• Molecule of heredity– Constitutes our genes– Genes are stretches of DNA sequence– DNA is present in each cell – Passed on to gametes and into progeny

What is DNA, Really

• Polymer of nucleotides

• Polymer? Nucleotides?

• Polymer– A large molecule that is a series of joined smaller

molecules• Nucleotides

– The small molecules that make up the large DNA polymer

DNA Concepts

• Genes• Chromosomes • Complementary base-paired double helix• Polymer of nucleotides• The sequence of nucleotides is the

information of DNA

DNA Concepts

• DNA controls traits of organism• Traits pass from parent to offspring • DNA is copied during cell division• DNA is present in sex cells • DNA is passed from parent to offspring

Why are DNA Concepts Difficult?

• Chemical names?– Deoxyadenosine, purine, pyrimidine

• Chemical processes?– base pairing, hydrogen bonds

• Genetic principles? – DNA replication– Mutations– Chromosome segregation & assortment

Why is DNA So Difficult?

• Chemical Names– Deoxyadenosine monophosphate– Pyrimidine

• Persons Names– Martina Navratilova– Hakeem Olajuwon

How About Pictures + Names

__ Hakeem Olajuwon __ Purine__ Kareem Abdul-Jabbar__ Deoxyadenosine monophosphate__ Pyrimidine__ Martina Navratilova__ Deoxycytidine monophosphate

__ Nadia Comaneci

A B C

E

F G HA

B

C

D

D

F

E

G

H

NucleotidesThe building blocks of DNA

Base always attached here

Phosphates are attached there

Nucleotide Structure

Adenosine monophosphateCytidine monophosphateGuanosine monophosphateUridine monophosphate

Deoxyadenosine monophosphateDeoxycytidine monophosphateDeoxyguanosine monophosphateDeoxythymidine monophosphate

Nucleotides

Nucleotide Polymerization Reaction: Phosphodiester Bond Formation

Order of Nucleotides

• As nucleotides join the strand they generate a sequence

• Inherent fidelity of DNA replication

AGTCCGATCGTAACTGGGTCACATCGTAAGTGTACACGTATCAGGCTAGCATTGACCCAGTGTAGCATTCACATGTGCAT||||||||||||||||||||||||||||||||||||||||AGTCCGATCGTAACTGGGTCAGGCTAGCATTGACCC|||||||||||||||||| TAAGTGTACACGTA

AGTGTAGC

TCACATCG

ATTCACATGTGCATTCACATCGTCAC

ATCGTCACAT

CGTAAGTGTACACGTATAAGTGTACACGTATAAGTGTACACGTA

AGTGTAGCAGTGTAGC

ATTCACATGTGCATATTCACATGTGCAT

||||||||||||||||||||||

ATTCACATGTGCAT

TAAGTGTACACGTA

DNA Sequence

• Human Genome Project– sequencing the human genome

• What does “sequencing” mean? – To determine the order of the nucleotides in the human DNA

molecules– Human DNA molecules are our chromosomes– Each chromosome is a DNA double helix– Each DNA double helix is two single DNA molecules intertwined– Each single DNA molecule is a chain of nucleotide units – Sequencing is the method to determine what the exact order of

units is in this chain

DNA

Gene

Transcription

Translation

RNA (messenger RNA)

Protein(sequence ofamino acids)

Functioning of proteins within livingcells influences an organism’s traits.

Gene Expression

A Gene is a Transcription Unit

DNA

mRNA 5

Promoter & Regulatorysequences

Terminator

Ribosome binding site

Transcription

Startcodon

Stopcodon

Open reading frame

3

Coding sequences

CodingTranscription

Overview of gene expression

A C

Translation

Translation Elongationaa-tRNA entry

Peptidyl transferase

Translocation Termination

Translation

The code is 3 letter words, but what about punctuation?

GROWANDNOWTHECATSAWTHEDOGBUTDIDNOTRUNENDSEW

• Code written in three letter words - codons • Ribosomes must start at the right place to read

the message• There are three frames, but only one is read to

give an intelligible message • Need a start codon (NOW) and a stop codon

(END) to define the frame to use• frame b

– NOW THE CAT SAW THE DOG BUT DID NOT RUN

acbb

Reading Frames & Mutation Types• Frame shift mutations

– Original reading frame is frame a– Insertions or deletions shift the reading frameROWANDNOWTHECATSAWTHEDOGBUTDIDNOTRUNENDSEW

abc

ROWNDNOWTHECATSAWTHEDOGBUTDIDNOTRUNENDSEWabc

^

Reading Frames & Mutations

• Once a ribosome begins translation in a particular frame (a) it does not shift frames

• Therefore, if a mutation shifts the reading frame in the mRNA, the ribosome will read the wrong frame.

ROWANDNOWTHECATSAWTHEDOGBUTDIDNOTRUNENDSEWabc

ROWANDNOWTHECATSAWTHEADOGBUTDIDNOTRUNENDSEWabc

^

NOW THE CAT SAW THE ADO GBU TDI DNO TRU NEN DSE W..

Reading Frames & Mutations

• A change that creates a stop codon is a non-sense mutation

• Generates a truncated protein

ROWANDNOWTHECATSAWTHEDOGBUTDIDNOTRUNENDSEWa

ROWANDNOWTHECATSAWTHEDOGBUTENDNOTRUNENDSEWa

^

NOW THE CAT SAW THE DOG BUT END

^

Reading Frames & Mutations

• A change that creates a different codon is a mis-sense mutation

• Generates a protein with an altered sequence

ROWANDNOWTHECATSAWTHEDOGBUTDIDNOTRUNENDSEWa

ROWANDNOWTHECATSAWTHEHOGBUTDIDNOTRUNENDSEWa

^

NOW THE CAT SAW THE HOG BUT DID NOT RUN END

Molecular Basis of Phenotype

Effect of Mutations

• Sickle cell disease– single nucleotide change AT