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Cell membrane
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the cell
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The tiny world of DNA
Chances are you've seen
an illustration of DNA's
double-helix structure
and even pictures of the
chromosomes that make
up the human genome.
But
• where and how does the
famous double helix fit
into chromosomes,
And
• how do chromosomes
relate to the human
body?
Our body contains ~100
trillion cells,
Excuding red blood cells,
which contain no nucleus
and no nuclear DNA,
every one of these cells
contains the human genome
-- a string of three billion
A's, C's, G's, and T's. And in
every one of the 100 trillion
cells, the sequence of these
four letters, or bases, is
nearly identical.
Although the DNA
code from cell to cell
is the same, there are
many different types
of cells within the
body, each with a
specific function.
For example, the long,
narrow muscle cell is
designed to contract,
and the squarish cell
that lines the wall of
the small intestine is
designed to filter
nutrients from food.
These cells are exact
copies of their parent cells.
But sometimes cells need to
become specialized.
Within the first month of
embryonic development,
cells are changing into
different forms, to form
different tissues.
This production of new
types of cells is the result of
DNA "turning on" and
"turning off" different
sections of the information
it stores.
Within every cell (except
red blood cells) is a
nucleus; a sphere-like
structure separated from
the rest of the cell by a
porous membrane.
The nucleus acts as the
cell's control center,
regulating its growth,
metabolism, and
reproduction.
At the heart of this
control centre is the
organism’s genome.
The human genome is
comprised of two sets of
23 chromosomes -- 46
chromosomes in total.
Each parent contributes a
set.
~97 percent of the genome
consists of sequences that
don't code for proteins and
have no known function.
Within the rest of the
genome are an estimated
70,000 genes.
The single chromosome
displayed here and those
on the previous screen are
shown in their most
compacted state -- they're
about to divide, along with
the cell, through the
process of mitosis.
When we see pictures of
chromosomes, this is
usually what we see. The
reason is that
chromosomes are most
visible during this time.
ΜΕΤΑΦΑΣΙΚΟ ΧΡΩΜΟΣΩΜΑ
CHO
HELA
HELA
85.000 βάσεις DNA ανά θηλιά
ΜΕΤΑΦΑΣΙΚΟ ΧΡΩΜΟΣΩΜΑ
When stained, chromosomes
show bands of light and dark
areas. The dark bands indicate
areas where the structure of the
chromosome is dense.
Each of the 23 chromosome
types has a unique banding
pattern. (A chromosome pair has
identical banding.)
In fact, scientists can identify a
chromosome based solely on its
banding pattern.
There's a lot of DNA within
the nucleus. To fit such a
long molecule within the tiny
space of the nucleus, DNA
bends and loops in several
ways. The largest of these
loops results from the helical
coiling of chromatin (the
thick line in this illustration).
This coiling causes the
chromosome to resemble a
spring.
Chromatin refers to
proteins that help organize
the long DNA
molecule.
The protein shown here
supports and organizes
small loops of DNA.
Zooming to see portions of the
DNA strand. The DNA is
wrapped around histones -protein structures that are
sometimes depicted as discs.
Histones carry a slight positive
charge, and DNA carries a
slight negative charge.
Since opposite charges attract,
the DNA is pulled in toward the
histones.
A nucleosome is a segment of
the DNA wrapped around a
core of histones.
ΝΟΥΚΛΕΟΣΩΜΑΤΑ
200 ζεύγη βάσεων ανά νουκλεόσωμα
Histone Protein Structure
Histones are the major structural proteins of chromosomes.
The DNA molecule is wrapped twice
around a Histone Octamer to make a Nucleosome.
ΔΟΜΗ &ΟΡΓΑΝΩΣΗ ΝΟΥΚΛΕΟΣΩΜΑΤΟΣ
Six Nucleosomes are assembled into a Solenoid in association with H1 histones.
The solenoids are in turn coiled onto a Scaffold, which is futher coiled to make the chromosomal matrix.
DNAcompaction[1]toWMV.wmv
Genes determine whether
you have brown eyes or
blue, long toes or short,
and much, much more.
Genes also control
everything from how your
cells grow to how they
interact with one another.
A single gene can range
in length from as few as
100 DNA bases to as
many as several million.
Simplified view of the
double helix
-- the subject of Rosalind
Franklin's Photo 51.
Shown here is the
structure of naked DNA - DNA without all of the
proteins that organize it
into chromatin.
Note how its structure
resembles a twisted
ladder. Note also that
DNA with a "left-handed"
twist, as this has, is a
special kind of DNA
known as Z-DNA.
The sides of the DNA ladder
consist of a long string of
sugar and phosphate
molecules,
to which the bases are
attached.
Each sugar-phosphate-base
combination is called a
nucleotide.
The DNA molecule is made
up of four bases
adenine (A),
cytosine (C),
guanine (G),
and thymine (T).
Each rung of the DNA
ladder consists of two bases.
In the DNA molecule,
A always pairs up with T,
and C always pairs up with
G.
A nucleotide is made up
of ~30 atoms,
Determining the
sequence of bases in the
human genome was such
an accomplishment.
And although the
sequencing is over,
understanding the
sequence is far from it.
Figuring out how these
3.000.000.000 bps code
for a human being is
another story
ΔΙΠΛΗ ΕΛΙΚΑ DNA & ΑΖΩΤΟΥΧΕΣ ΒΑΣΕΙΣ
Watson was 23 at the time!!!
A Structure for DNA
(typescript)
Watson & Crick [Nature 1953]
Rosalind Franklin took an exceptional X-ray photograph of a DNA molecule,
which provided Watson+Crick with the key to the double-helix puzzle.
Sodium deoxyribose nucleate from calf thymus,
Structure B, Photo 51, (May 2, 1952)
taken by Rosalind E. Franklin and R.G. Gosling
nucDNA
versus
mtDNA
Alternative Vertebrate Genomes: nuclear & mitochondrial DNA
The nucDNA genome in typical vertebrates consists of several billion base pairs of DNA,
arranged on paired chromosomes, one inherited from each parent.
The human genome shown here comprises 3 billion bp in 22 pairs of autosomal chromosomes and one pair of sex chromosomes, XY in this (male) individual.
The mtDNA genome is a much smaller, circular molecule about 16 ~ 18,000 bp in circumferance in most vertebrate species.
The genome comprises 13 protein-coding regions, two rRNA genes, a replication control region, and 22 tRNA genes.
The order of these is broadly conserved across vertebrates. There are no introns: splicing out of tRNAs produces mRNA templates.
The mtDNA genome is self-replicating with the aid of nucDNA-encoded polymerases.
The genome is locted is the extranuclear mitochondria, the "powerhouses of the cell," where it contributes to cell respiratory systems
in the Cytochrome Oxidase, ATP synthase, and NADH systems. The vertebrate mtDNA genetic code differs from the "Universal" code is several respects.
Unlike the nucDNA genome, the mtDNA genome is inherited solely through the cytoplasm of the maternal egg,
and does not undergo genetic recombination. It has therefore been widely used in evolutionary and population biology
to trace maternal lineages within and between species.
The Chloroplast Genome
The genome of the chloroplasts found in Marchantia polymorpha (a liverwort, one of the
Bryophyta) contains 121,024 base pairs in a closed circle.
These make up some 128 genes which include:
•duplicate genes encoding each of the four subunits (23S, 16S, 4.5S, and 5S) of the ribosomal
RNA (rRNA) used by the chloroplast
•37 genes encoding all the transfer RNA (tRNA) molecules used for translation within the
chloroplast.
• Some of these are represented in the figure by black bars (a few of which are labeled).
•4 genes encoding some of the subunits of the RNA polymerase used for transcription within the
chloroplast (3 of them shown in blue)
•a gene encoding the large subunit of the enzyme RUBISCO (ribulose bisphosphate
carboxylase oxygenase)
•9 genes for components of photosystems I and II
•6 genes encoding parts of the chloroplast ATP synthase
•genes for 19 of the ~60 proteins used to construct the chloroplast ribosome
All these gene products are used within the chloroplast, but all the chloroplast structures also
depend on proteins
•encoded by nuclear genes
•translated in the cytosol, and
•imported into the chloroplast.
RUBISCO, for example, the enzyme that adds CO2 to ribulose bisphosphate to start the Calvin
cycle, consists of multiple copies of two subunits:
•a large one encoded in the chloroplast genome and synthesized within the chloroplast, and
•a small subunit encoded in the nuclear genome and synthesized by ribosomes in the cytosol.
The small subunit must then be imported into the chloroplast.
The arrangement of genes shown in the figure is found not only in the Bryophytes (mosses and
liverworts) but also in the lycopsids (e.g., Lycopodium and Selaginella).
In all other plants, however, the portion of DNA bracketed by the red arrows on the left is
inverted. The same genes are present but in inverted order.
The figure is based on the work of Ohyama, K., et al., Nature, 322:572, 7 Aug 1986; and Linda
A. Raubeson and R. K. Jansen, Science, 255:1697, 27 March 1992.
The evolution of eukaryotic chloroplasts by the endosymbiosis of cyanobacteria seems to have
occurred on three different occasions producing as separate events:
•the green algae and plants as described above
•red algae
•glaucophytes; a small group of unicellular algae
ΟΡΓΑΝΩΣΗ ΓΟΝΙΔΙΟΥ
The largest known gene is associated with Duchenne muscular dystrophy
(2.4 million bases in length)
ΑΡΙΘΜΟΣ ΒΑΣΕΩΝ ΣΤΟ ΓΟΝΙΔΙΩΜΑ ΟΡΓΑΝΙΣΜΩΝ
ΣΥΓΚΡΙΣΗ ΑΛΛΗΛΟΥΧΙΩΝ
Look for genes
Functions
Genetic variation
Evolutionary relationships
BLAST (Basic Local Alignment Search Tool)
BLAST Search Terminology
Sequence ID: A unique number used to
identify the DNA sequence.
Description: Describes the species from
which the sequence comes and the gene it
is associated with (if any).
Query: Indicates how many bases are in
the input (test) sequence.
Match: The amount of shading on each
graphic indicates how well the query
sequence matches the hit (or subject)
sequence. Note, the shading does not
compare the similarities between the
whole genomes.
Expected (E) Value: Result of a
mathematical calculation that describes
the significance of a match. The lower the
E value (closer to“0”), the better the
match. An E value of less than 10-6 is a
biologically significant match.
CLUSTAL
Cystic fibrosis
For multiple alignments
Map and sequence the genomes of model organisms
bacterium E. coli (4.6 million)
yeast S. cerevisiae (12 million)
roundworm C. elegans (100 million)
fruitfly D. melanogaster (180 million)
mouse M. musculus (3 billion)
The approximate number of base pairs in each species’ genome is given in parentheses.
HUMAN GENOME PROJECT
15 year project sequence 3.2 billion bases
• begun in 1990
took 4 years to sequence 1 billion bases
took 4 months to sequence the 2nd 1 billion bases
In January 2003, 1.5 billion bases were sequenced
In 1993: 10 dollars per base
In April 2003: 10 cents per base
1997: E. coli Genome Sequenced
1998: M. Tuberculosis Bacterium Sequenced
1998: Genome of Roundworm C. elegans Sequenced
1999: Chromosome 22
2000: Free Access to Genomic Information
2000: Chromosome 21
2000: Drosophila and Arabidopsis genomes sequenced
2001: First Draft of the Human Genome Sequence Released
2002: Mouse Genome Sequenced
2002: Rice Genome Sequenced
2003: Human Genome Project Completed
2003: ENCODE Program Begins
2004: Rat and Chicken Genomes Sequenced
2004: Refined Analysis of Complete Human Genome Sequence
2005: Chimpanzee Genomes Sequenced
2005: Trypanosomatid Genomes Sequenced
2005: Dog Genomes Sequenced
2006: The Cancer Genome Atlas (TCGA) Project Started
2006: Second Non-human Primate Genome is Sequenced
2006: Initiatives to Establish the Genetic and Environmental Causes of Common
Diseases Launched
THE FUTURE
Sequence data are piling up
Need better methods for analysis
Improved software
Acquisition
Storage
Analysis
THE FUTURE
Collect and distribute data
Distribute genomic information to the research community.
Release all sequence data that spans more than 2000 base pairs within 24 hours.
Create and run databases.
Develop software for large-scale DNA analysis.
Develop tools for comparing and interpreting genome information.
Share information with the wider public.
Develop technologies
Make large-scale sequencing faster and cheaper.
Develop technology for finding sequence variations.
Develop ways to study functions of genes on a genomic scale.
Study the ethical, legal and social implications of genetic research
Transfer technology to the private sector