Total length of DNA ~ 2 x 1014 km Circumference of the earth 4 x 104 km Distance between the earth and the sun

1.5 x 108 km

GENOME: Total DNA in an organism Human genome ~ 3 bi bp Worm 100 mi bp Fruit fly 160 mi bp Yeast 15 mi bp

Genomics
Application of high throughput automated molecular biology technologies Study of large number of genes & gene products taking advantage of complete genome sequence All at once in whole cells, whole tissues or whole organism A who listic or systems approach to the study of information flow within a cell

Knowledge of specific genes underlying diseases & differences in Individuals genetic make up that respond to differently to drugs, are changing the face of drug development & delivery

323 bacterial genome have been sequenced 235 sequences belong to different species 65 sequences of type strains 32 sequenced more than once of the same species
1350 more sequencing projects in progress Impact of bacterial genomics bioinformatics second generation genomic technologies on target identification assay development lead optimization compound characterization

Genomics: a revolution in the making

First genome sequence of a complete organism (bacterium):
Haemophilus influenza,1995 first free-living organism
Mycoplasma genitalium, 1995 470 proteins

First genome sequence of an archaeum: Methanococcus

jannaschii, 1995 ~1,700 proteins

First genome sequence of a complete multicellular organism:

Caenorhabditis elegans, 1998 ~18,000 proteins 25-30,000 proteins

Human genome sequence: 2001

-second mammal, mouse genome -- others- over 300s of bacteria/archaea, plants, animals, zebrafish

- provides complete information about what makes up an organism but: we know the functions of <50% of all genes

Genome

Ordered library
Random small-insert library of whole genome Sequence and contig assembly Random small-insert library of one clone Sequence and contig assembly Repeat for other clones Assemble complete genome sequence Assemble complete genome sequence

Shotgun sequence

Clone- by- clone-approach

SEQUENCING

FIRST-GENERATION GEL-BASED SEQUENCE ANALYSIS

Capable of sequencing small regions Y chromosome: 50 Mb; Chromosome 1: 250 Mb

50,000 -100,000 b/year @ $1-2/b

SECOND-GENERATION SEQUENCING TECHNOLOGIES

Sequence 100,000 b/d @ $ 0.20 to 0.50/b Faster, more sensitive, accurate

THIRD-GENERATION GEL-LESS TECHNOLOGIES

Fluorescence detection of bases by flow cytometry

Scanning tunneling or atomic force microscopies Mass spectroscopic analysis Sequencing by hybridization

Functions of protein

NUCLEIC ACIDS 4 NUCLEOTIDES

PROTEINS
20 AMINO ACIDS 2 20

4 4

2=

16
200

= 400 =
420 2

100

=2

100 20

AMINO ACIDS
O H2N

DI-PEPTIDE
O H C R2 COOH H2N H C R1 H2N O O H C R2

H C
R1

C OH

+H

N H

C N H

H C R2

COOH O H C R3 C OH

H2O

TRI-PEPTIDE

H2N

H C R1

C N H

C N H

H C R3

COOH

O
H2N H C C N H H C

O C N H Rn -2 H C COOH POLYPEPTIDE

R1

Rn

GENETIC CODE
U C A G UUU UUC UUA UUG Phe Phe Leu Leu UCU Ser UCC Ser UCA Ser UCG Ser UAU Tyr UAC Tyr UAA End UAG End UGU Cys UGC Cys UGA End UGG Trp

CUU CUC CUA CUG

Leu Leu Leu Leu

CCU Pro CCC Pro CCA Pro CCG Pro

CAU His CAC His CAA Gln CAG Gln

CGU Arg CGC Arg CGA Arg CGG Arg

AUU AUC AUA AUG

Ile Ile Ile Met

ACU Thr ACC Thr ACA Thr ACG Thr

AAU Asn AAC Asn AAA Lys AAG Lys

AGU Ser AGC Ser AGA Arg AGG Arg

GUU GUC GUA GUG

Val Val Val Val

GCU Ala GCC Ala GCA Ala GCG Ala

GAU Asp GAC Asp GAA Glu GAG Glu

GGU Gly GGC Gly GGA Gly GGG Gly

The primary structure of a protein is its linear sequence of amino acids and the location of any disulfide (-S-S-) bridges.

SECONDARY STRUCTURE
Most proteins contain one or more stretches of amino acids that take on a characteristic structure in 3-D space. The most common of these are the alpha helix and the beta conformation. Alpha Helix
The R groups of the amino acids all extend to the outside. The helix makes a complete turn every 3.6 amino acids. The helix is right-handed; it twists in a clockwise direction. The carbonyl group (-C=O) of each peptide bond extends parallel to the axis of the helix and points directly at the -N-H group of the peptide bond 4 amino acids below it in the helix. A hydrogen bond forms between them [-N-HO=C-] .

BETA CONFORMATION
Consists of pairs of chains lying side-by-side and Stabilized by hydrogen bonds between the carbonyl oxygen atom on one chain and the -NH group on the adjacent chain. The chains are often "antiparallel"; the N-terminal to C-terminal direction of one being the reverse of the other

FOUR-RESIDUE BHAIRPINS
These are also quite common with the first two residues adopting the alphahelical conformation. The third residue has psi and phi angles which lie in the bridging region between alpha-helix and beta-sheet and the final residue adopts the left-handed alpha-helical conformation and is therefore usually glycine, aspartate or asparagine.

TERTIARY PROTEIN STRUCTURE AND FOLDS

There are a number of examples of small proteins (or peptides) which consist of little more than a single helix. A striking example is alamethicin, a transmembrane voltage gated ion channel, acting as a peptide antibiotic.

Quaternary Structure of Protein

Structures of Proteins

FOUR NUCLEOTIDES OF DNA

DNA-1 ATGAAGGCCTTAAAAGAGCTTTCCCAATTTCTAG.. DNA-2 GGTTAACGTTAGGGGGAACCAAGTGGAATTGATA..

DNA MICRO ARRAY

Sickle cell anaemia- due to change in one base pair CCTGATCC (Valine)

CCTGTTCC(Glutamine)