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Transcript
Organization of Chromosomes--Study Guide
and Outline
Broad course objective: a.) explain the molecular structure of
chromosomes as it relates to DNA packaging, chromosome function
and gene expression
Necessary for future material on: Chromosome Variation, Regulation
of Gene Expression
DNA Packaging—Why and How
• If the DNA in a typical human cell were stretched out, what length would
it be? What is the diameter of the nucleus in which human DNA must be
packaged?
• What degree of DNA packaging corresponds with “diffuse DNA”
associated with G1? What kind of DNA packaging is associated with Mphase (“condensed DNA”)?
• What types of DNA sequences make up the genome? What functions do
they serve?
• What are the differences between euchromatin and heterochromatin?
• What types of proteins are involved in chromosome packaging?
–
–
How do nucleosomes and histone proteins function in DNA packaging?
What is chromosome scaffolding?
How much DNA do different organisms have?
Organism
T4 Bacteriophage
HIV
E. colibacteria
Yeast
haploid genome in bp
168,900
9,750
4,639,221
13,105,020
Lily
36,000,000,000
Amoeba
290,000,000,000
Frog
3,100,000,000
Human
3,400,000,000
DNA content does not directly coincide with complexity of the
organism. Any theories on why?
Size measurements in the molecular world
• 1 mm (millimeter) = 1/1,000 meter
• 1 mm (“micron”) = 1/1,000,000 of a
meter (1 x 10-6)
• 1 nm (nanometer) = 1 x 10-9 meter
•1 bp (base pair) = 1 nt (nucleotide pair)
•1,000 bp = 1 kb (kilobase)
•1 million bp = 1 Mb (megabase)
•5 billion bp DNA ~ 1 meter
•5 thousand bp DNA ~ 1.2 mm
Representative genome sizes
• Phage virus: 168 kb  65 nm phage head
(~1,000 x length)
• E. coli bacteria: 1,100 mm DNA  ~0.2
micron space nucleoid region (5,500 x)
• Human cell: 7.5 feet of DNA  ~3 micron
nucleus (2.3 million times longer than the
nucleus)
DNA packaging: How does all that DNA fit
into one nucleus?
(Equivalent to fitting 690 miles of movie film into a 30-foot room)
An organism’s task in managing its DNA:
1.) Efficient packaging and storage, to fit into
very small spaces (2.3 million times smaller)
2.) Requires “de-packaging” of DNA to access
correct genes at the correct time (gene
expression).
3.) Accurate DNA replication during the Sphase of the cell-cycle.
Chromosomal puffs in condensed Drosophila chromosome show
states of de-condensing in expressed regions
Prokaryotic genome characteristics
1. Circular chromosome (only
one), not linear
2. Efficient—more gene DNA,
less or no Junk DNA
3. One origin sequence per
chromosome
How does the bacterial chromosome
remain in its “tight” nucleoid without a
nuclear membrane?
Bacterial chromosome is normally
supercoiled
(~ 40 kb)
Bacterial DNA released from
supercoiling
Bacterial DNA Supercoiling
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Levels of DNA Packaging in Eukaryotes
Types of DNA sequences
making up the eukaryotic genome
DNA type
Unique-sequence
Function
Number/genome
Protein coding and non-coding
1
Repetitive-sequence
Opportunistic?
Centromere
Cytoskeleton attachment
Telomere
C’some stability
few-107
1 region/c’some
Ends of c’some DNA
Centromere sequences
•Repeating sequences
•Non protein-coding
•Sequences bind to centromere proteins, provide anchor
sites for spindle fibers
Reminder of function of kinetochores and
kinetochore microtubules
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Chromosome
fragments
lacking
centromeres are
lost in mitosis
(Figure 11.10)
Telomere sequences function to preserve
the length of the “ends”
Dolly: First successful cloned adult
animal
Born on July 5,
1996, Dolly died on
February 14, 2003.
Dolly suffered from
lung disease, heart
disease and other
symptoms of
premature aging.
Telomeres sequences may loop back and
preserve DNA-ends during replication
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Major proteins necessary for chromosome
structure
Protein type
Function
Histone
packaging at 11nm width, nucleosome formation
Linker proteins
packaging at 11nm width, nucleosome formation
Scaffold
“Skeleton” of the condensed mitotic c’some
Kinetochore
Cytoskeleton attachment to centromere
Telomerase
enzyme for preserving lengths of telomeres in stem
cells (covered in DNA Replication chapter)
Telomere caps
degradation
protects ends of linear chromosomes from
Levels of DNA Packaging in Eukaryotes
Digestion of
nucleosomes
reveals
nucleosome
structure
Nucleosome structure
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
•Positively charged
histone “tails” bind
to DNA.
•Acetylation of
histone proteins 
allows access to
DNA
COCH3--
-COCH3
-COCH3
Transcription
Factor
Levels of DNA Packaging in Eukaryotes
Arrangement of 30-nm chromatin
fiber into looped domains
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Eukaryotic DNA “released” from its tight packaging
as a metaphase chromosome (only scaffold
remains)
Go over lecture outline at end of
lecture