DNA, gen, kromosom dan genom

Megga Pikoli
Retrieved from various sources
Observations of cells and embryos in the late 9th century had led to
the recognition that the hereditary information is carried on chromosomes,
threadlike structures in the nucleus of a eucaryotic cell that become visible by
light microscopy as the cell begins to divide.

Later, as biochemical analysis became possible, chromosomes were found to

consist of both deoxyribonucleic acid (DNA) and protein.

For many decades, the DNA was thought to be merely a structural element.
However, the other crucial advance made in the 1940s was the identification of
DNA as the likely carrier genetic information.
A DNA Molecule Consists of Two Complementary
Chains of Nucleotides
 DNA Denaturation
When an aqueous solution of DNA is heated at 100'C or exposed to a very high
pH (pH≥ 13), the complementary base pairs that normally hold the two strands of
the double helix together are disrupted and the double helix rapidly dissociates
Into two single strands. This process, called DNA denaturation, was for many
years thought to be irreversible. In 1961, however, it was discovered that
complementary single strands of DNA readily re-form double helices by a process
called hybridization (also called DNA renaturation) if they are kept for a
prolonged period at 65"c.
So…
What is a gene?

(in technical use) a gene is a distinct sequence of nucleotides forming part of a

chromosome, the order of which determines the order of monomers in a
polypeptide or nucleic acid molecule which a cell (or virus) may synthesize
The Structure of DNA Provides a Mechanism for
Heredity
Numbers and types of genes in different eukaryotes

About half the genes encode proteins of unknown function

How about chromosome?
What is so special about chromosomes ?

1. They are huge: One bp = 600 dalton, an average

chromosome is 107 bp long = 109- 1010 dalton ! (for
comparison a protein of 3x105 is considered very big.
2. They contain a huge amount of non- redundant information
(it is not just a big repetitive polymer but it has a unique
sequence).
3. There is only one such molecule in each cell. (unlike any
other molecule when lost it cannot be re-synthesized from
scratch or imported)

Therefore philosophically - the cell is there to serve,

protect and propagate the chromosomes.
The organization of genes of a human chromosome
Conservation between human and mouse genomes
Usually important genes are encoded by conserved regions
Note: Human chromosome 1 and mouse chromosome 4

human mouse
centromere
DNA molecule not only carries genetic information, but
also undergoes conformational change

• Chromosomes exist through the cell cycle

• Single chromosome can only be visible during mitosis
Chromosomes at interphase and M phase

A. Interphase; B. Mitosis.
Mitotic chromosomes are condensed and organized.
Three important DNA sequences
Telomere, replication origin, centromere
 The DNA compaction problem
• Can you imagine to take 4 meters of DNA (string) and
compact them into a ball of 10m?

• Therefore DNA molecules are highly

condensed/compacted in chromosomes

• This compaction is very complex and the DNA isn’t just

crammed into the nucleus but is organized in a very
orderly fashion from the smallest unit - the nucleosome,
via loops, chromosomal domains and bands to the entire
chromosome which has a fixed space in the nucleus.
Nucleosome: basic level of chromosome/chromatin organization
Chromatin: protein-DNA complex
Histone: DNA binding protein
DNA is compacted by histones to form nucleosomes
 Histone
•Linker histone: H1
•Core (octamer) histones : H2A, H2B, H3, H4

Histone octamer :
2 H2A
2 H2B
2 H3
2 H4
A: diameter 30 nm; B: further unfolding, beads on a string conformation
 The bending of DNA in a nucleosome

There are at least 3 things:

1. Flexibility of DNAs: G-C riched minor groove outside
and A-T riched minor groove inside
2. the function of Histone tails
3. DNA-binding-protein can also help the bending of DNA
in a nucleosome
Zigzag model of the 30-nm chromatin fiber
Higher order
compactions
Chromosomes
p (petit)
= Short arm
p
Centromere

q q = Long arm

Chromosome no. 5
Banding Pattern of human
chromosomes
Giemsa Staining
Green line regions:
centromeres

Encoding ribosome
A pair of homologous chromosomes (number 1) as seen
at metaphase
Locus (position of a gene or
DNA marker)

Allele (alternative form of a

gene/marker)
 Total Genes On Chromosome: 723
373 genes in region marked red, 20 are shown
FZD2
AKAP10
ITGB4
KRTHA8
WD1 Genes are arranged in linear order on
SOST chromosomes
MPP3

MLLT6

STAT3
BRCA1 breast cancer 1, early onset
GFAP
NRXN4
NSF
NGFR
CACNB1
HOXB9
HTLVR
ABCA5
CDC6
ITGB3
Chromosome 17
source: Human Genome Project
A polytene chromosome from Drosophila salivary gland

Electron Microscope image of Drosophila polytene chromosome:

Light bands
Replicate early in S phase
Less condensed chromatin
Transcriptionally active
Gene and GC rich

Dark (G) bands

Replicate late
Contain condensed chromatin
AT rich
Genome is the sum total of an organism's DNA
– All the DNA on all the chromosomes
– Includes genes, intergenic sequences, repeats

• Specifically, it is all the DNA in an organelle.

• Eukaryotes can have 2-3 genomes

– Nuclear genome
– Mitochondrial genome
– Plastid genome

• If not specified, “genome” usually refers to the nuclear

genome.
Genome Complexity
 Genome sizes

Gene density down in

mammals
Human genome: individuals 99.9% identical
For every 1000 people . . .

Sequencing revealed one major allele for most

genes in populations

Human populations have not been genetically

isolated for very long (~2-3 M years)

Many variations have not had time to spread

throughout populations.
Please learn
the detail
by yourself…