dna – molecular genetics. dna structure – review…… -dna is made of monomers called...

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DNA – Molecular Genetics

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Page 1: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

DNA – Molecular Genetics

Page 2: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

DNA STRUCTURE – Review……

- DNA is made of monomers called nucleotides.

- Nucleotides consists of - 5 carbon sugar- Phosphate group- Nitrogenous base (A,T,C,G)

- Backbone- made of covalent bonds between bonds between the phosphate and sugar

- “Rungs of Ladder” – made of pairs of nitrogenous bases.

A-T C-G

Page 3: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Nitrogenous Bases In DNA, there are 4 types of bases

Page 4: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

STRUCTURE-

- Sides of Ladder – Sugar/Phosphate backbone

- Rungs of Ladder – Base Pairs

- Two strands of DNA are connected through weaker Hydrogen bonds that form between bases

- Only certain bases can form these hydrogen bonds with each other

-They are called complementary

Page 5: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

How many hydrogen bonds between

C-G?

A-T?

Would A-G be possible????

Page 6: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

CHARGAFF’S RULE

Amount of Adenine = The amount of Thymine

Amount of Guanine = The amount of Cytosine

If a sample of DNA contained 16% adenine……….?

PURINES = PYRIDAMINES

Page 7: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

What does DNA need to be able to do?

Be copied– every time a cell divides

DNA Replication

Be “read” – every time we need to make a protein.

Transcription

Page 8: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

DNA REPLICATION

Overview Semi-conservative

Molecule opens up Each side is a template to build a

complementary side End up with two DNA molecules, each

one half old and half new.

Page 9: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Step 1 Unzipping the DNA Enzyme called helicase which breaks the

hydrogen bonds between the base pairs. OPENS THE MOLECULE UP!

Step 2 Complementary Base Pairing Each of the DNA strands can now act as

templates to construct complimentary sides. Enzyme DNA polymerase attaches

complementary nucleotides to each of the open strands

Page 10: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Semi-Conservative Replication

- Each of the resulting DNA molecules are identical to each other and each contains one original strand and one new one.

Page 11: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Not that simple though…… Antiparallel strands….

The two sides of the DNA molecule run in opposite directions. The 5 and 3 refer to the orientation of the ribose molecule

Page 12: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Because they are anti-parallel….

The copying can only happen in one direction along the

35 side of the template.

Leading strand

- Built continuously as fork opens

Lagging Strand

- Built in fragments,

- Needs patching together by ligase

Page 13: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group
Page 14: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group
Page 16: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Replication Bubbles

DNA is LOOOOOOOOONNNNNNGGGGGG!

In order to speed-up copying, replicate in several places at once.

Page 17: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

RNA vs. DNA

3 Main Differences Single Stranded Sugar in RNA is ribose In RNA, thymine is

replaced by uracil

Why use these replacements????? CHEAPER!!!!

Page 19: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

3 types of RNA

Messenger (mRNA) carries the RNA copy of the DNA gene out of the nucleus to the ribosomes.

Ribosomal (rRNA) make-up portion of the ribosome.

Transfer (tRNA) bring individual amino acids to the ribosome for assembly into polypeptides.

Page 20: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

2 key steps to making proteins

Transcription

- Copy DNA code on mRNA

Translation

Reading the mRNA molecule code and turning it into a polypeptide chain (linking together amino acids)

Page 21: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Transcription

Goal: Copy DNA code (gene) onto an mRNA molecule.

Steps:

1. Helicase opens DNA molecule at specific section (gene)

2. Enzyme RNA polymerase binds to a promoter site (specific base sequence) just before the gene sequence

3. RNA polymerase moves along gene sequence and creates a complementary RNA strand

Page 23: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

When RNA polymerase reaches terminator sequence (specific base sequence), new RNA molecule released from DNA molecule

mRNA molecule travels to the cytoplasm where the message will be translated into polypeptides

YOU TRY IT!

Transcription

Page 24: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Difference in cell types?

In eukaryotes, mRNA transcript has to be modified before leaving the nucleus to be translated. RNA EDITING!

SIGNIFIGANCE – One gene can code for many different proteins!!!! Introns – What gets cut out (stay in the nucleus) Exons – What gets left it (Exits the nucleus)

In prokaryotes, the mRNA is ready to go No Editing Needed!

Page 25: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

RNA EDITING

Exons vs. Introns

Page 26: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Translation

Goal: mRNA Polypeptide (will be a protein once the 3D folding occurs)

Review

Proteins made by linking together amino acids

20 different amino acids

Sequence of amino acids going to determine protein properties (shape).

So how can a code of 4 letters (bases) code for 20 different amino acids?

Page 27: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

The Genetic Code

In the genetic code, three bases will code for one amino acid

Why 3? 4^3 = 64 different combinations with nucleotide triplets, compared with 4^ 2 = 16 different combinations with pairs. Would 2 bases be enough???

The three bases that code for a specific amino acid are called codons

ONE CODON = ONE AMINO ACID!!!!

Page 28: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Translation

Codons- You are responsible for knowing 4:

AUG

UAA, UAG, UGA

Page 29: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Translation - Interpreting the Code

Sequence of mRNA GGUACGUCCCCA

Read as GGU-ACG-UCC-CCA

Page 30: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group
Page 31: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Translation (the details)

The players

mRNA – code for making polypeptide

rRNA – ribosome - assembles polypeptide

tRNA – transfers amino acids to ribosome for assembly

All RNA made by the NUCLEOLUS

Page 32: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

tRNA and rRNA structure/function

tRNA is a folded RNA strand

- amino acid on one end- anti-codon on the other end

rRNA makes up part of the ribosomes - ribosomes made of rRNA and protein- Consists of two subunits

Page 33: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Translation in action…..

Best to watch a video first

Simple http://www.stolaf.edu/people/giannini/flashanimat/molgenetics/tr

anslation.swf

Complex

http://highered.mcgraw-hill.com/olc/dl/120077/micro06.swf http://www.johnkyrk.com/DNAtranslation.html

Page 34: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Overall Process Initiation

Start codon read, first tRNA binds to mRNA bringing methionine

Ribosome assembles

Elongation See animations for detail Chain builds

Termination Stop codon reached Whole assembly falls apart Polypeptide formed

Page 35: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Mutations

Mistakes happen!

Sometimes during DNA replication, bases can get inserted, removed or switched!!

Changes in the DNA base sequence are called MUTATIONS!!!

Can be single nucleotides – Point Can be whole chunks of DNA- Chromosomal

Page 36: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Point Mutations

One base in the sequence is affected

Substitution – one base switched out for another

Insertion – base put into code

Deletion – base removed from code

Page 37: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Point - Substitution

If this happens on a gene portion of the DNA molecule, it can result in a change in one of the amino acids in a polypeptide sequence.

Page 38: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Point - Insertion/Deletion

When a base is inserted or deleted, much bigger changes

Changes like this are called frame shift mutations shift the reading frame of the genetic code. (how

we read it)

These mutation affect all amino acids that follow the mutation point

Page 39: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Example of frameshift

Page 40: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Point - Substitutions

Missense mutations new nucleotide alters the codon so as

to produce an altered amino acid in the protein product. Can cause big changes in

polypeptide if new amino acid in chain is chemically different than the one it replaced.

Can be neutral if new amino acid is chemically similar to one it replaced.

Page 41: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Point - Substitutions (cont.) Nonsense mutations

With a nonsense mutation, the new nucleotide changes a codon that specified an amino acid to one of the STOP codons (TAA, TAG, or TGA).

Significance?

The earlier in the gene that this occurs, the more truncated (shortened) the protein product and the more likely that it will be unable to function.

Page 42: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Point - Silent mutations

Most amino acids are encoded by several different codons.

For example, if the third base in the TCT codon for serine is changed to any one of the other three bases, serine will still be encoded. Such mutations are said to be silent because they cause no change in their product

Page 43: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Chromosomal Mutations

Involve large-scale changes to structure or number of a chromosome!

Have much greater consequences than point mutations WHY???

MANY GENES AFFECTED!!!!

Page 44: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group
Page 45: DNA – Molecular Genetics. DNA STRUCTURE – Review…… -DNA is made of monomers called nucleotides. -Nucleotides consists of -5 carbon sugar -Phosphate group

Mutations-

So all mutations are bad right?????