Human genome sequence

DNA = DEOXYRIBONUCLEIC ACID

RNA = RIBONUCLEIC ACIDStrong acid hydrolyses DNA & RNA into 3 components:

• nitrogenous base (4 different ones)

• sugar

• phosphoric acid

Mild acid hydrolyses DNA & RNA into 2 components:

•Nucleoside = base—sugar

•Nucleotide = base-sugar-phosphate

DNA & RNA are polymers of nucleotides

keto (carbonyl)

amino

amino

NUCLEOTIDE structure: nitrogenous bases

PURINE1

2

3

4

5

8

9

76

N

N N

N

H

H

N

N N

N

NH2

ADENINE — A

H

H

N

N N

N

O

H2N

GUANINE — G

methyl

amino keto (carbonyl)

keto (carbonyl)

NUCLEOTIDE structure

PYRIMIDINEN

N1

3

2

4

5

6

CYTOSINE — C

H

NH2

O

N

N

THYMINE — T

H

O

O

HN

N

CH3

URACIL— U

H

O

O

HN

N

First difference between DNA and RNA:

DNA contains the bases A, G, C and T

RNA contains the bases A, G, C and U

NUCLEOTIDE structure

2. THE SUGARS — pentoses

O

OHOH

OH

H

CH2

H

HO

1

2

4

3

5

D-ribose (RNA)

O

OHOH

OH

H

CH2

H

HO

1

2

4

3

5

H

D-2-deoxyribose (DNA)

Second difference between DNA and RNA:

DNA contains 2-deoxyribose

RNA contains ribose

NUCLEOTIDE structure

3. PHOSPHORIC ACID

O

P OHHO

OH

(H3PO4)

Phosphoric acid

O

P OHO-

O-

pH 7

(HPO42-)

Phosphate ion

NUCLEOSIDE = base—sugar

N

NN

N

NH2

adenineO

OHOH

H

CH2

H

HO

ribose

DEOXYADENOSINE = adenine—deoxyribose

deoxy

H

NUCLEOTIDE structure

Base—sugar—phosphate

N

NN

N

NH2

adenineO

OHOH

H

CH2

H

HO

ribose

e.g. ADENOSINE

Adenosine 5'-monophosphate

(5'-AMP)

O

O

PO-

O-

5'

The 3' and 5' positions are very important for understanding DNA and RNA structure and function

NUCLEOSIDE numbering

O

OHOH

H

CH2

H

HO

N

N

O

NH2

5

4

3 2

1

6

5

4

3

2

1

'

'

'

'

'

"Prime" mark: '

O

OHOH

H

CH2

H

HO

ribose

N

NN

N

NH2

adenine5'

Adenosine 5'-monophosphate (5'-AMP)

O

O

PO-

O-

O

O

PO-

O-

Adenosine 5'-diphosphate (5'-ADP)

O

O

PO-

O-

Adenosine 5'-triphosphate (5'-ATP)

How are mononucleotides linked together to form the polymers DNA and

RNA?

3',5'-phosphodiester bond

N

N

O

NH2

O

OHOH

H

CH2

H

HO

5'O

3'

N

N

O

NH2

O

OHOH

H

CH2

H

HO

3'

5'O

O

P

O-

O

O

O

P

O-

N

N

O

NH2

O

OHOH

H

CH2

H

HO

5'O

O

P

O-

O

3'

N

N

O

NH2

O

OHOH

H

CH2

H

HO

3'

5'O

O

P

O-

O

O

OHOH

H

CH2

H

HO

5'O

O

P

O-

O

3'

N

NN

N

NH2 A

C

C

Single-stranded polynucleotides have one free 5' end and one free 3' end — they exhibit POLARITY

POLARITY

DNA is a double helix

•Studies of DNA hydrolysis showed that the repeating unit was a NUCLEOTIDE

• CHARGAFF's "rules"

What information did Watson and Crick use in 1953 to arrive at their "double

helix" structure for DNA?

%A = %T

%G = %C

%A = %T

%G = %C

%G = %(C + 5-MeC)

Plants have a particularly high content of 5-MeC

H

N

N N

N

NHCH3

6-methylADENINE

Note that in addition to the bases A,G, C and T there are some minor bases found in DNA

H

NH2

O

N

N

CH3

5-methylCYTOSINE

prokaryotes and eukaryotes prokaryotes

helical structure with repeats at 0.34 and 3.4 nm

2 nm wide

phosphates on outside of structure

Density of chain suggests the helix contains 2 strands

Conclusion: DNA MUST be double-stranded

X-ray diffraction patterns obtained by Wilkins, Franklin & Gosling showed:

1.08 nm

1.08 nm

N

N

N

N N

N

NH

H

O

O

H3C H

H

H

A

T

AT base pair

N

N

N

N N

N

O

H

N

N

O

H

H

H

HH

HH

C

G

GC base pair

2 H-bonds

3 H-bonds

Double helical DNA

3.4 nm:

One helical turn

0.34 nm

2 nm 2 nm

Major groove

Minor groove

sugar-phospha

te backbon

e

Base pairs "stacked" vertically in interior10 bp

per turn

Both strands coiled round a common axis

5'

3'5'

3'

Strands are ANTIPARALLEL

One runs 5' to 3'

Other runs 3' to 5'

Watson & Crick solved the structure of DNA in 1953

"...A structure this pretty just had to exist." - James Watson in The Double Helix

The implications of the ‘Double Helix’

Based on the fact that DNA is the genetic material:

Stable

Faithful replication and propagation of life– Two strands: one can form the template for DNA

replication

Faithful transmission of information to RNA– One strand acts as template

RNA then transfers information to proteins

http://science.nhmccd.edu/biol/bio1int.htm

DNA replication

Protein Structure

Amino acid structure

N C

O

OHH

HH

R

C

R is a chemical group that varies in different amino acids.

C is central “chiral” carbon.

Non-polar amino acids

Polar amino acids

Peptide bonds result

from dehydration

of A.A.s

Primary structure is the

sequence of A.A.s

Sickle-cell anemia cause

Secondary structure

Tertiary structure

Quaternary structure

If all cells come from other cells where did the first ‘life’ come from?

The Miller-Urey experiment

Water is heated in a closed apparatus containing methane (CH4), ammonia (NH3) and hydrogen (H2) and an electric discharge is passed through the mixture.

Many precursors can be produced in simple pre-biotic conditions

• Some amino acids found (building blocks for proteins)

• Some nucleic acids found e.g. adenine• Some sugars found including ribose