Organization of Eukaryotic DNA Dr: Hussein abdelaziz

Objectives

By the end of lecture the student should:

Identify DNA organization

Define gene and genome.

Recognize types of genes

Describe Human Genome Project

Chromatin

chromosomal material extracted from nuclei of

eukaryotic cells

Consists of:

1- Very long double stranded DNA molecule (1.7

m long)

2- Proteins involved in folding/packing eukaryotic

chromosomes and consists of:

A- Histone proteins: basic proteins

B- Non-histone proteins: regulatory proteins

including enzymes & regulatory factors of

transcription.

3- Small amount of RNA

Histones

Five classes of histones,

H1, H2A, H2B, H3 & H4

These small proteins are

positively charged at

physiologic PH as a

result of their high

content of lysine and

arginine so they form

ionic bonds with

negatively charged

phosphate group in DNA

Functions of Histones

1- Compacting DNA strands: the compacting

molecule is 40,000 times shorter than an

unpacked molecule

2- Chromatin regulation: modified histone have

important role in biological processes as: Gene regulation

DNA repair

Chromosome condensation

3- Conserved packing material of DNA:

important in chromosome stabilization and

gene expression

1-Formation of nucleosomes

Nucleosome is formed of a histone core of 8 molecules

of histones, 2 H2A, 2 H2B, 2 H3, & 2 H4, around which a

segment of DNA double helix is wrapped nearly twice left

handed super helical turns

Organization of the DNA double strand in nucleosomes

make it to look like beads in a string, the 10 nm fiber

Neighboring nucleosomes are joined by Linker stretch

of DNA (approximately 50 base pairs), & is covered by 1

molecule of H1, thus completing 2 DNA turn

H1 is the most tissue-specific & species specific of the

histone. It facilitates the packing of nucleosomes into

more compact structures

Linker DNA

2-higher level of organization

Nucleosomes can be packed more tightly to form a

polynucleosome (6-7 Nucleosomes per turn) to form

30nm fiber also called nucleofilament which look like

solenoid (cylindrical coil)

The 30 nm fiber is

organized into loops

that are anchored by a

nuclear scaffold

containing several

proteins

(scaffold proteins e.g

topoisomerase II) to give

700 nm structure

Additional levels of

organization lead to the

final chromosomal

structure (1400 nm)

2 nm

30 nm

300 nm

700 nm

1400 nm

10 nm

Levels of DNA

packaging

1- 2 nm double

stranded

molecule

2- 10 nm

nucleosomes

3- 30 nm fiber

Organization

around a

central scaffold

Chromosomes

During metaphase, DNA can

be seen under microscope

as super packed

chromosomes, where

identical sister chromatides

are connected at the

centromere (8,000 fold

shorter than primary B-form)

In human, 23 pairs of

chromosomes are

found & numbered

according to their

length and position of

centromere

In Somatic cells: genome is

diploid. Thus, each human

somatic cell contains 22

pairs of homologous

autosomal chromosomes & 2

sex chromosomes XX in

female or XY in male.

In gametes (ova, sperm):

genome is haploid. Thus the

human gametes contain 22

autosomal chromosomes

and one sex chromosome, X

in female gamete or Y in

male gamete

Gene & Genome

Gene is the fundamental unit of hereditary

It's a segment of DNA on a specific position (Locus) on

chromosome

Each gene is a part of DNA sequences that contains

genetic information coding for synthesis of one

polypeptide (protein)

Genome is the total number of genes within one mature

cell of an organism

Only about 10% of the human DNA contains genes. The

remaining 90% of DNA are as important as regulatory and

identity functions

A) House keeping genes: these genes are essential for

cell life

They are integral parts of the cells e.g. hexokinase

gene that essential for glucose metabolism inside

every cell

B) Differential (specific function) genes: these are

genes that essential for performance of specific

functions and so differ in each organ e.g. genes

specific for liver functions will only be expressed in

the liver cells, genes for insulin will be active in beta

cells of pancreas only

Types of genes

Is an international project aiming for

sequencing and localization of each

gene along the human genome

started 1990 & the rough copy of

HGP was obtained June 2000

Through this project the following

information can be obtained:

a) The function & site of each gene

along specific chromosomes

b) A genetic finger-print or a gene map

for each individual can be done through

which we can predict susceptibility or

resistance to various diseases

Human Genome project (HGP)

In almost all organism, the flow of genetic

information goes in one direction from the

stored gene code in DNA by transcription into

a message copy as mRNA that is then

translated into a protein that carry out the gene

function

DNA to DNA → Replication

DNA to RNA → Transcription

RNA to protein →Translation

Flow of genetic information

Retroviruses (RNA viruses as AIDS virus) are

viruses that have at their core RNA as the

genetic information not DNA

Therefore, the mechanism of flow of genetic

information is reversed i.e. from RNA into DNA

then into mRNA then protein

Flow of genetic information

Questions