Honors BiologyChapter 12

Molecular Genetics

Identify key historical findings in the pursuit of the structure of DNA.

Draw and label a diagram of the molecular structure of DNA, showing the relationships between the six essential molecules that make up DNA: deoxyribose, phosphate, adenine, cytosine, guanine, thymine.

Apply knowledge of complementary base pairing to predict a DNA strand sequence given information about the other DNA strand.

What IS the physical “factor” identified by

Mendel?How do “factors” produce phenotypes? What is the molecular basis for the “genetic code?”

Scientists could narrow it down to molecules found in the nucleus: DNA, RNA, or protein?

Most thought proteins, because they’re much more diverse and complex

Griffith’s Transformati

onWorking with pneumonia in 1928, Griffith transformed or changed bacteria from one form to another.

Avery’s ExperimentsWhat is the “transforming factor”?

Avery used enzymes to destroy molecules from the heat killed cells before transforming harmless cells.

Concluded: DNA is the transforming factor.

Hershey-Chase Experiment

Alfred Hershey & Martha Chase: Radioactively label viral protein vs. DNA, let the phages infect bacteria, then separate them

Bacteria had the DNA trace, not the protein trace

Rosalind Franklin & Photo 51

Franklin used X-ray diffraction to photograph crystallized DNA molecules.

Showed the helical shape and repeating structure of DNA

The Double Helix

In 1953, James Watson and Francis Crick used scientific evidence reported by other scientists to suggest a model for the DNA structure as a double helix

Nucleic Acids

Examples DNA

Deoxyribonucleic Acid

RNA Ribonucleic Acid

RNA

Information molecules

DNADNA

Nucleic Acids Function:

genetic material stores information

blueprint for building proteins DNA RNA proteins

transfers informationblueprint for new cellsblueprint for next generation

proteinsproteins

Nucleic acids

Building block = nucleotides

5 different nucleotides different nitrogen bases A, T, C, G, U

nucleotide – nucleotide – nucleotide – nucleotide

phosphate

sugar N base

Nitrogen basesI’m the

A,T,C,G or Upart!

4 Types of Nitrogenous Bases in DNA

Purines: have 2 rings (Adenine and Guanine)

Pyrimidines: have 1 ring (Thymine and Cytosine)

Complementary Base Pairing

Chargaff’s Base Pairing Rule: Chargaff determined that the amount of Adenine = amount of Thymine, and the amount of Guanine = the amount of Cytosine.The bases are connected to each other in the double helix by hydrogen bonds.

A pairs with T C pairs with G

DNA Double strand twists into a double helix

Hydrogen bonds between nitrogen bases that join the 2 strands are weak

the two strands can separate and reattach

with relative ease

Describe and model the process of DNA replication, including an explanation of why it produces identical copies of DNA.

Copying DNA A dividing cell replicates (i.e. duplicates)

its DNA in S phase creates 2 copies of all DNA (sister

chromatids) separates the 2 copies to 2 daughter cells

nucleus

cell

DNA

Copying DNA Matching bases allows

DNA to be easily copied

DNA Replication Steps:

DNA starts as a double-stranded molecule matching bases (A:T, C:G)

Then the helix untwists and…

DNA replication Strands “unzip” at the weak bonds

between bases Done by an enzyme, helicase

DNA replication

DNA polymerase

Enzyme DNA polymerase

matches free-floating bases to exposed strand

DNA basesin nucleus

New copies of DNA Get 2 exact copies of DNA to split between new

cells, thanks to complementary base pairing Each copy = one original strand, one new strand

DNA polymerase

DNA polymerase

Copying DNA

DNA Replication-Review

• This process is responsible for the formation of sister chromatids, and their characteristic X shape

double-strandedhuman chromosomesready for mitosis

From Gene to Protein

Compare and contrast DNA and RNA. Explain and model the overall process of protein synthesis (transcription and translation).

Apply knowledge of transcription to predict an mRNA sequence given information about a DNA sequence.

DNA Proteins Cells Bodies

proteinscells

bodiesDNA gets all the glory,Proteins do all the work

What do we know? DNA

DNA = instructions for proteins

Proteins proteins run living organisms enzymes

all chemical reactions in living organisms are controlled by enzymes (proteins)

structure all living organisms are built out of proteins

Protein Synthesis: Part 1

So… How does the cell get the instructionsfrom the nucleus to the ribosomes?

DNA – stores info to make proteins

RIBOSOMES – where proteins are made

CYTOPLASM

NUCLEUS

Where are proteins made?Where are the instructions to make proteins?

CELL

It makes a copy to send called – messenger RNA

mRNA

Flow of Genetic Information

1. A gene or segment of DNA is located on a chromosome

2. The cell uses transcription to copy the gene into a piece of mRNA

3. The mRNA leaves the nucleus and goes to a ribosome

4. The ribosome uses translation to direct the assembly of a protein

5. Gene is now expressed in the cell

RNA = Ribonucleic Acid

Structure: Made of a single strand of nucleotides

Nucleotides use Ribose instead of Deoxyribose

Nitrogen base thymine is replaced by Uracil

Types:Messenger RNA (mRNA): single stranded- used to carry DNA code out of nucleus “working copy”

Transfer RNA (tRNA): binds to specific amino acids, used to build proteins

Ribosomal RNA (rRNA): makes up ribosomes along with proteins

DNA vs. RNADNA

deoxyribose sugar nitrogen bases

G, C, A, T T = thymine

T : A C : G

double stranded

RNA ribose sugar nitrogen bases

G, C, A, U U = uracil

U : A C : G

single stranded

DNA vs. RNA

DNA

DNARNA

Transcription Making mRNA from DNA DNA strand is the

template (pattern) match bases

U : A G : C

Enzyme RNA polymerase

Matching bases of DNA & RNA Double stranded DNA unzips

A G GGGGGT T A C A C T T T T TC C C CA A

Matching bases of DNA & RNA Double stranded DNA unzips

A G GGGGGT T A C A C T T T T TC C C CA A

Matching bases of DNA & RNA Match RNA bases to DNA

bases on one of the DNA strands

U

A G GGGGGT T A C A C T T T T TC C C CA A

U

UU

U

U

G

G

A

A

A C CRNA

polymerase

C

C

C

C

C

G

G

G

G

A

A

A

AA

Matching bases of DNA & RNA U instead of T is matched to A

TACGCACATTTACGTACGCGGDNA

AUGCGUGUAAAUGCAUGCGCCmRNA

Transcription Steps1. RNA Polymerase binds to the promoter (specific place

for polymerase to bind) on the DNA and begins transcription

2. DNA strands separate or unzip. 3. One of the original strands serves as a template. RNA

polymerase binds new RNA nucleotides to the template strand following base pairing rules. (A-U, C-G)

4. mRNA leaves the nucleus and carries the instructions to the ribosomes. The DNA “re-zips”.

A – T C – G G – C A – T C – G

T – A

A - - T C - - G G - - C A - - T C - - G T -

- A

A - U - T C - G - G G -

C - C A - U - T C - G - G T -

A - A

A – T U C – G G G – C C A – T U C – G G T – A A1 2 3 - 4 5

Explain and model the overall process of protein synthesis (transcription and translation).

Apply knowledge of translation to predict a tRNA sequence given information about an mRNA sequence.

Apply knowledge of translation to predict an amino acid sequence given information about a tRNA sequence.

RNA to protein But… building blocks are mismatched.

RNA “language” = 4 bases. Protein “language” = 20 amino acids.

aa aa aa aa aa aa aa aa

How do you convert from one language to another?

mRNA

U C CCCCCA A U G U G A A A A AG G G GU U

But there’s still the 4 to 20 problem…

TACGCACATTTACGTACGCGGDNA

AUGCGUGUAAAUGCAUGCGCCmRNA

Met Arg Val Asn Ala Cys Alaprotein

?

AUGCGUGUAAAUGCAUGCGCCmRNA

Solution: mRNA codes for proteins in triplets

TACGCACATTTACGTACGCGGDNA

AUGCGUGUAAAUGCAUGCGCCmRNA

Met Arg Val Asn Ala Cys Alaprotein

?

Codon block of 3 mRNA nucleotides

that “codes” for one amino acid

codons

Now, how are the codons matched to amino acids?

TACGCACATTTACGTACGCGGDNA

AUGCGUGUAAAUGCAUGCGCCmRNA

aminoacid

tRNAanti-codon

codon

UAC

MetGCA

ArgCAU

Val

ribosome

mRNA to protein = Translation The message -> mRNA The reader ribosome The transporter transfer RNA (tRNA) The product -> polypeptide/protein

aaaa

aa

tRNA

mRNAU C CCCCCA A U G U G A A A A AG G G GU U

GGU

aa

tRNA

U A C

aa

tRNA

GA C

tRNA

aa

A GU

Transfer RNA

Transfer RNA (tRNA) A folded RNA chain, with

three exposed bases (anticodon) and an amino acid Which amino acid it

carries depends solely on the anticodon

Function: Carry amino acids to ribosome, assemble them in correct order

Translation Steps1. Initiation: Ribosome attaches to the mRNA at the start

codon (AUG)2. tRNA with the complementary anti-codon (UAC) binds

to the mRNA codon, bringing the amino acid methionine with it.

3. Ribosome shifts down the mRNA to the next codon.4. Elongation: Another tRNA with the complementary anti-

codon binds to the mRNA codon. The amino acid from the tRNA binds to methionine.

5. The ribosome shifts again, another tRNA brings another amino acid to bind to the growing amino acid chain.

6. Termination: Process continues until the ribosome reads a stop codon, at which time it releases the finished amino acid chain (AKA: protein)

In Animated Format

http://www-class.unl.edu/biochem/gp2/m_biology/animation/gene/gene_a3.html

http://learn.genetics.utah.edu/content/begin/dna/transcribe/

http://www.dnatube.com/video/5934/Basic-explanation-of-mRNA-Translation

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter3/animation__protein_synthesis__quiz_3_.html

All life on Earth uses the same code

Due to common origin

Code is redundant several codons for

each amino acid “mutation

insurance!”

Start codon AUG methionine

Stop codons UGA, UAA, UAG

Genetic Code

The Genetic Code

A map of CODONS, not ANTIcodons

Recap of Protein Synthesis

A gene = a region of the chromosome that codes for one protein

mRNA is made in the nucleus using DNA as a template. (TRANSCRIPTION) mRNA travels to ribosome.

Protein is made at the ribosome by matching tRNA to mRNA. (TRANSLATION)

Amino acid sequence determines protein’s shape, protein shape determines its function.

“Central Dogma” of Molecular Genetics

DNA -> RNA -> Protein -> Trait

Expanded version:DNA -> mRNA -> tRNA -> amino acid sequence -> protein

shape -> protein function -> trait

tran

scri

ptio

n

tran

slat

ion

Mutations

Distinguish between point/substitution and frameshift/insertion/deletion mutations, and predict their effects on an amino acid sequence.

Mutations Mutations are changes in DNA sequences,

usually as errors in replication different DNA order = different RNA order =

different protein = different trait Human germ cell line averages 35

mutations per generation

Bb bbBB

Mutations Point or Substitution

mutations single base change Ex: T instead of C Can be:

silent mutation no amino acid change

due to redundancy in code

missense change amino acid

nonsense change to stop codon

Example: Sickle cell anemia

Sickle cell anemia Autosomal codominant/recessive inheritance pattern Strikes 1 in 3 Subsaharan Africans, 1 in 500 African

Americans Sickle-shaped red blood cells carry less oxygen, easily

“clog” blood vessels

Mutations Frameshift

shift in the reading frame changes everything

“downstream” Tends to have more

profound effects than point mutations

insertions adding base(s)

deletions losing base(s)

THE RAA TAN DTH ECA TAT ETH ERE DBA T

Frameshift mutationsTHE RAT AND THE CAT ATE THE RED BAT

THE RTA NDT HEC ATA TET HER EDB AT

(Point)

THE RQT AND THE CAT ATE THE RED BAT

Example: Cystic fibrosis

Primarily Northern and Western European descent strikes 1 in 2500 births

1 in 25 white Europeans are carriers (Aa) normal allele codes for a membrane protein

mutant channel limits movement of Cl- (& H2O) across cell membrane

thicker & stickier mucus coats cells in lungs, pancreas, digestive tract

without treatment children die before 5; with treatment can live past their late 20s

Mutations

Mutation = not necessarily bad. As a phenomenon, is essential to genetic

diversity. And individual mutations… can be beneficial (ex: a fur color protein that

more closely matches environment) can be neutral (ex: silent mutations) can be detrimental (ex: cystic fibrosis) can be beneficial and detrimental! (ex: sickle

cell anemia protects against malaria)