Download Chapter 5 DNA and Chromosomes

Chapter 5
DNA and Chromosomes
DNA as the genetic material
Heat-killed bacteria can transform living cells
S  Smooth
R  Rough
Fred Griffith, 1920
DNA is the genetic material
Oswald Avery
Colin MacLeod
Maclyn McCarty
1935
1. The first evidence that DNA
could serve as the genetic material
2. The genetic material was likely
to be made of protein
Genes are made of DNA
Martha Chase
Alfred Hershey
1952
The empty viral coats
T2 virus Radioactively
label
(w/o S)
(w/o P)
The Nobel Prize in Physiology or Medicine 1969
The replication mechanism and the genetic structure of viruses
What is gene?
Genes – the information-containing elements that determine the characteristics of a species
as a whole and of the individuals within it.
A gene is usually defined as a segment of DNA that contains the instructions for
making a particular protein (or, in some cases, a set of closely related proteins).
What is genome?
Genome – the totality of DNA genetic information in each cell is called its genome.
= 3.2x109 nucleotides.
What is chromosome?
Chromosomes – in eucaryotic cells, very long double-strand DNA molecules
are packaged into structure called chromosomes.
Homologous chromosomes (homologs)
Homologus chromosomes – the maternal and paternal chromosomes of a pair.
Chromosomes become visible as cells prepare to divide
DAPI DNA staining
Nucleotide
DNA is made of four nucleotide building blocks
Sugar-phosphate backbone
Polynucleotide chain
Antiparallel
The two strands of the DNA double helix are hold together
by hydrogen bonds between complementary base pairs
Base pair
Antiparallel
5’-PO4
3’-OH
5’-PO4
3’-OH
A space-filling model shows the conformation
of DNA double helix
10 bases/turn
P
O
H
N
Genetic code
Genetic code – the exact correspondence between the 4-letter nucleotide alphabet of DNA
and the 20-letter amino acid alphabet of proteins
Transcription and translation
Linear messages come in many forms
Gene contain information to make proteins
Each human chromosome can be “painted” a
different color to allow its unambiguous identification
under the light microscope
DNA hybridization
Karyotype
Karyotypes - The homologus chromosomes are numbered and arranged in pairs
Unique banding patterns allow the identification
of the human chromosomes
Giemsa stain
A-T rich
centromere
rRNAs
centromere
Abnormal chromosomes are associated with
some inherited genetic defects
Ataxia / Chromosome 12
Chromosome 4
Genes are arranged along the chromosomes
Junk DNA
Gene
Closely related species can have very different
chromosome numbers
The two species shown have roughly the same number of genes
The cell cycle
The replication and segregation of chromosomes occurs
through an ordered cell cycle in proliferating cells
microtubules
G0/G1
S
G2
M
Three DNA sequence elements are needed to produce
a eucaryotic chromosome that can be replicated
then segregation at mitosis
x2
x1
Replication origin
DNA Replication
Centromere
The role of telomere in life span
A typical mitotic chromosome is highly compact
Mitotic chromosome
SEM
Interphase chromosomes occupy different territories
within the nucleus
The nucleolus is the most prominent structure
in the interphase nucleus
(Chromosome13, 14, 15, 21, 22)
TEM
Nucleolus
Nucleolus – The parts of the different chromosomes carrying genes for ribosomal RNA (rRNA)
cluster together.
Heterochromatin & Euchromatin
Heterochromatin – The most highly condensed form of interpahse chromatin
is called heterochromatin.
DNA in interphase chromosome is less compact than
that in mitotic chromosomes
Interphase nuclear DNA
Mitotic chromosome
TEM
Nucleosomes can be seen in the electron microscope
Chromatin
30-nm thick
Unpacked, decondensed
“beads-on-a-string”
Nucleosome
Nucleosome
core particle
DNA
TEM
Chromatin
Chromatin – The complex of both classes of protein with nuclear DNA.
Most of the chromatin is in the form of fibers, each with a diameter of about 30 nm.
Nucleosome
Nucleosome – The first and most fundamental level of chromatin packing.
Histones
Nucleosomes contain DNA wrapped around
a protein core of eight histone molecules
High proportion of
positively charged
amino acids
(lysine and arginine)
80bp
Negatively-charged
sugar-phosphate backbone
of DNA
The structure of the nucleosome core particle, as
determined by X-ray diffraction analysis, reveals how DNA
is tightly wrapped around a disc-shaped histone core
Highly conserved
1.7 turns in a left-handed coil
N’
N’
A linker histone helps to pull nucleosomes together
into the 30-nm fiber
DNA packing occurs on several levels in chromosomes
Interphase chromatin
Mitotic chromasome
+ Histone H1
The mitotic chromosome is formed from
tightly packed chromatin
SEM
Chromosome & Chromatids
Chromatin-remodeling complexes reposition the DNA
wrapped around nucleosomes
DNA-binding proteins
The pattern of modification of histone tails can dictate
how a stretch of chromatin is treated by the cell
To bind specific proteins
N’
Methyl group (+)
Acetyl group (-)
Phosphate (-)
Interphase chromatin
Heterochromatin: 10%
Euchromatin: 90%
Expression of a gene can be altered by moving it to
another location in the genome
(expression)
Position effect
(non-expression)
An X chromosome can be inactivated
by heterochromatin formation
Double dose of X-chromosome prodicts
would be lethal
The structure of chromatin varies along
a single interphase chromosome
How histone modifications may be inherited
by daughter chromosomes
Restore the parental modification
Epigenetic inheritance
Epigenetics – The study of heritable changes in gene expression or cellular phenotype caused
by mechanisms other than changes in the underlying DNA sequence.