INTRODUCTION TO GENETICS

Genetics is the study of heredity, the process in which a parent passes certain gene onto their children. A person's appearance – height, hair color, skin color, and eye color -- are determined by genes.

Gene: a gene is a nucleotide sequence in DNA that specifies a polynucleotide or RNA.

History

• 1946 – DNA is the main constituent of genes (Avery)• 1950 – First X-ray pictures of DNA (Franklin)• 1953 – DNA structure revealed (Watson and Crick)• 1970 onwards - Multiple conformations and structures, initially from

fibers• 1973 - X-ray structure confirms double helix (Rich)• 1974 - t-RNA structure (Kim)• 1980 – Structure of first complete turn of B DNA (Dickerson)

Location of DNA

In Prokaryotes:- DNA is not separated from the rest of cellular components.

In eukaryotes :- DNA is located in the nucleus , and separated from the rest of the

cell by nuclear envelope.

DNA is bound to proteins forming a complex called chromatin.

Less than 0.1% of the total DNA in a cell is present in mitochondria.

Euchromatin= diffuse chromatinHeterochromatin= dense chromatin

P= petit (small)

Chromosome

23 pairs of chromosomes

In eukaryotic cells, a linear structure composed of a single DNA molecule complexes with protein.

Chromosome Number in Various Organisms

Organism Total Chromosome Number

Human

Chimpanzee

Dog

Cat

Mouse

Mosquito

Potato

Tomato

46

48

78

72

40

6

48

24

Histones

Electron micrograph of nucleosomes Attached by strands of nucleic acid.

Solenoid

H2A dimer

H2B dimer

H3-H4 tetramer

DNA Strands

Watson and Crick’s double-helical model of DNA

1. The DNA molecule consists of two polynucleotide chains wound around each other in a right-handed double helix

2. The two chains are antiparallel.

3. The sugar-phosphare backbones are on the outsides of the double helix, with base orientated toward the central axis.

4. The bases in each of the two polynucleotide chains are bonded together by hydrogen bonds. The specific pairings observed are A bonded with T (2 hydrogen bonds) and G bonded with C ( 3 hydrogen bonds) and its according to Chargaff’s rule. They are called complementary base pairs. 5.The base pairs are 0.34 nm apart in the DNA helix. A complete turn (360˚) turn of the helix takes 3.4 nm, therefore there are 10 base pairs per turn. 6.

Determination of structure of DNA DNA is composed of nucleotides.

Nucleotides is composed of a base, a sugar and phosphate.

PO

O

O-

O O

CC

C C

H

H

H

OH

H

CH2

1

23

4

5Base

BASE

Uracil (U) instead of Thymine in RNA.

Purine Pyrimidine

• Adenine (A)

• Guanine (G)

Cytosine (C)

Thymine (T)

SUGAR

Deoxyribose (DNA)

Ribose (RNA)

O

CC

C C

H

O H

H

OH

H

CH2

1

23

4

5

OO

CC

C C

H

H

H

OH

H

CH2

1

23

4

5

O

C

CHO

OHH

OHCH

CH2OH

OHCH

D-Ribose

C

CHO

OHH

OHCH

CH2OH

OHCH

D-Ribose

Reduction

C

CHO

HH

OHCH

CH2OH

OHCH

2-deoxy-D-Ribose

Alpha and Beta Anomers

C

CHO

OHH

OH C H

CH2OH

OHCH

OHCH

D-Glucose

C OHH

OH C H

CH2OH

CH

OHCH

Alpha-D-Glucose

C OHH

O

C OHH

OH C H

CH2OH

CH

OHCH

Beta- D-Glucose

COH H

O

Hemiacetal linkage formation Hemiacetal linkage formation

Differ in configuration of –OH group on anomeric carbon atom.

The Glycosidic Bond• Connects ribose sugar to the base

O-glycosides: when hydroxyl group on anomeric carbon of a sugar reacts

with an alcohol (sugar) O-glycoside is formed.

O-glycosidic linkage is present in disaccharides and polysaccharides.

So, disaccharides, oligosaccharides and polysaccharides are O-glycosides.

N-glycosides

N-glycosides: when hydroxyl group on anomeric carbon of a sugar reacts

with an amine N-glycoside is formed.

N-glycosidic linkage is present in nucleotides, RNA and DNA.

So, nucleotides, RNA and DNA are examples of N-glycosides.

Nucleotides

Monomeric units of nucleic acids.

Each nucleotide consists of a heterocyclic nitrogenous base,

a pentose sugar and phosphate.

Base

C

O

C

C C

H

OH

H

OH

H

CH2

1

23

4

5

Sugar

PO

O

O-

O

Phosphate

PO

O

-O-

PO

O

O-

PO

O

O-

O

CC

C C

H

OH

H

OH

H

CH2

1

23

4

5

O Base

Nucleoside

Nucleoside monosphosphate (NMP)

Nucleoside diphosphosphate (NDP)

Nucleoside triphosphosphate (NTP)

Nucleotides

BASE NUCLEOTIDE

Adenine (A)

Guanine (G)

Cytosine (C)

Thymine (T)

Uracil (U)

Adenosine

Guanosine

Cytidine

Thymidine

Uridine

C

NH2

Adenine

C

CC CH

H

H

N

N

N

N

1

2

34

5

67

9

C

O

Guanine

C

CC CH

H

H

N

N

N

N

1

2

34

5

6

8

7

98

C

NH2

Cytosine (C)

CH

CHC

N

NH

1

2

34

5

6

O

C

O

Thymine (T)

C-CH3

CHC

HN

NH

1

2

34

5

6

O

• • •A

GC

T

T

CG

A

• • •• • •• • •

• • •A T

• • • C

• • • AT

G

• • •AG

C

T

T

C

G

A

• • •• • •• • •

• • •A

GC

U

U

CG

A

• • •• • •• • •

• • •A U

• • • C

• • • AU

G

• • •AG

C

U

U

C

G

A

• • •• • •• • •

Base pairing

Hydrogen bonds

H

H

CC

CN

NC

N

C

N

N

H

H

H

Adenine

1

23

4

6 5

7

8

9

CC

C

CN

N

O

H

CH

HH

Thymine

12

3

45

6

N

Cytosine

H

H

H

CC

C

CN

N

H

H

H

ON

CC

CN

NC

N

C

N

O

H

Guanine

H

3‘ end

5‘ end3‘ end

5‘ end

5’ end

Phosphate backbone

PO

O

O

CH2O

-

PO

O

O

CH2O

-

PO

O

O

CH2O

-

Phosphodiester bonds

Phosphodiester bonds

3’ end

PO

O

O

CH2O

-

O

DNA Strands Are Antiparallel

5’ end

PO

O

O

CH2O

-

PO

O

O

CH2O

-

P O

O

O

CH2 O

-

3’ end

PO

O

O

CH2O

-

P O

O

O

CH2 O

-

5’ end

5

3

PO

O

O

CH2O

-

5

3P O

O

O

CH2 O

-

5

3

P O

O

O

CH2 O

-

3’ end

5

3

5’-carbon of the sugar is above 3’-carbon: The strand is said to run in 5’to 3’ direction.

3’-carbon of the sugar is above 5’-carbon: The strand is said to run in 3’to 5’ direction.

The two strands run in opposite direction.

Angstrom Unit= 0.1 nanometer

The A form, which predominates in DNA-RNA hybrids, is similar to the B form , but is more compact.

In the Z form, the bases of the two DNA strands are positioned toward the periphery of a left-handed helix.It is designated “Z” because, in each strand , a line connection the phosphates “zigs” and “zags”.

Predominates in vivo Predominates in DNA-RNA hydrinds

Types of DNA

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