Trends in Biotechnology
150402 TB 10 DNA from the
Beginning - Genetic Organization and
Control
Concept 29 - DNA is packaged in a chromosome.
Work on cytology in the late 1800s had shown
that each living thing has a characteristic set of
chromosomes in the nucleus of each cell. During
the same period, biochemical studies indicated
that the nuclear materials that make up the
chromosomes are composed of DNA and
proteins. In the first four decades of the 20th
century, many scientists believed that protein
carried the genetic code, and DNA was merely a
supporting "scaffold."
Just the opposite proved to be true. Work by
Avery and Hershey, in the 1940s and 1950s,
proved that DNA is the genetic molecule. Work
done in the 1960s and 1970s showed that each
chromosome is essentially a package for one
very long, continuous strand of the DNA. In
higher organisms, structural proteins, some of
which are histones, provide a scaffold upon
which DNA is built into a compact chromosome.
The DNA strand is wound around histone cores,
which, in turn, are looped and fixed to specific
regions of the chromosome.
• Animation at
http://www.dnaftb.org/29/animatio
n.html
• The review problem is at
http://www.dnaftb.org/29/problem.
html
Photo of chromatin
digested by nuclease,
from Hewish and
Burgoyne's 1973
experiment.
Electron micrograph of the 10-nm fiber.
Electron micrograph of the 30-nm fiber
Electron
micrograph of the
DNA and the
protein scaffold left
over from one
chromosome
(insert) with all the
histone stripped
out.
• Living things have a characteristic set of
chromosomes in the nucleus of each cell.
• Biochemical studies indicated that the
nuclear materials that make up the
chromosomes are composed of DNA and
proteins.
• Each chromosome is a package for one
very long, continuous strand of the DNA.
• In higher organisms, structural
proteins, some of which are
histones, provide a scaffold upon
which DNA is built into a compact
chromosome.
• The DNA strand is wound around
histone cores, which, in turn, are
looped and fixed to specific regions
of the chromosome.
Concept 30 - Higher cells have an ancient
chromosome.
In addition to the set of chromosomes found in
the nucleus, a different type of chromosome is
found in the energy-generating organelles of the
cytoplasm, the mitochondria. The mitochondrial
(mt) chromosome contains genes involved in the
process of oxidative phosphorylation — the
production and storage of energy.
There is evidence that mitochondria once
existed as free-living bacteria, which were taken
up by primitive ancestors of eukaryotic cells. The
primitive host cell provided a ready source of
energy-rich nutrients, and the mitochondrion
provided a means to extract energy using
oxygen. This symbiotic relationship became key
to survival, as oxygen accumulated in the
primitive atmosphere.
Mitochondria are physically
similar in size to bacteria, and
the mt genome retains
bacteria-like features. Like
bacterial chromosomes, the
mt genome is a circular
molecule. Also, very few
introns are found in mt genes.
Plants contain an additional
ancient chromosome in the
chloroplasts, which were also
absorbed as symbionts.
•Animation at
http://www.dnaftb.org/30/animation.
html
•The review problem is at
http://www.dnaftb.org/30/problem.ht
ml
Concept 31 - Most DNA does not encode
protein.
In most cases when DNA is extracted from living
cells, the proteins (including histones) are
dissolved away. This results in long strands of
naked DNA, which retain their genetic
information. So it is useful to visualize a
chromosome as a continuous strand of DNA.
Arrayed along the DNA strand are the genes,
specific regions whose sequences carry the
genetic code for making specific proteins.
The genes of bacteria are tightly packed
together; virtually all the DNA encodes
proteins. However, experiments done in
the 1960s, showed that a large proportion
of eukaryotic DNA is composed of
repeated sequences that do not encode
proteins. Long non-coding sequences — or
intergenic regions — separate relatively
infrequent "islands" of genes.
Research in the 1970s
showed that numerous
non-coding sequences —
introns — are also found
within genes, interrupting
the protein-coding regions,
or exons.
It is estimated that only
about five percent of
human DNA encodes
protein.
•Animation at
http://www.dnaftb.org/31/animation.
html
•The review problem is at
http://www.dnaftb.org/31/problem.ht
ml
Concept 32 - Some DNA can jump.
In the 1950s, Barbara McClintock showed
that certain DNA fragments, termed
transposons, can be activated to transpose
("jump") from one position on a
chromosome to another. She hypothesized
that transposition provides a means to
rapidly reorganize genes in response to
environmental stress.
McClintock's work was remarkable, not
only because it went against prevailing
ideas, but also because it was based
entirely on observation of chromosomes
and genetic crosses. Confirmation of her
ideas had to await the discovery of the
modern tools of DNA analysis. This work
paved the way for the modern concept of
chromosomes as dynamic, changing
structures.
Alu is an example of a so-called "jumping gene" a transposable DNA sequence that "reproduces"
by copying itself and inserting into new
chromosome locations.
http://www.dnalc.org/resources/animations/alu
.html
•Animation at
http://www.dnaftb.org/32/animation.html
•The review problem is at
http://www.dnaftb.org/32/problem.html
•Animation and quiz
•http://highered.mcgrawhill.com/sites/0072995246/student_view0/chapter23/mechanism_of_transposition.html
•http://highered.mcgrawhill.com/sites/0072995246/student_view0/chapter23/simple_transposition.html
•http://highered.mcgrawhill.com/sites/0072995246/student_view0/chapter23/transposons__shifting_segments_of_the_
genome.html
Concept 33 - Genes can be turned on and off.
As researchers studied the genetic code and the
structure of genes in the 1950s and 60s, they
began to see genes as a collection of plans, one
plan for each protein.
• But genes do not produce their proteins all
the time -> Organisms can regulate gene
expression.
• French researchers studied gene regulation
using bacteria.
When lactose is
available, E. coli turn
on a set of genes to
metabolize the sugar.
Lactose removes an
inhibitor from the
DNA.
Removing the
inhibitor turns on
gene production.
The gene that produces the inhibitor is
a regulatory gene.
Cells not only have genetic plans for
structural proteins within their DNA,
they also have a genetic regulatory
program for expressing those plans.
•Animation and quiz at
www.sumanasinc.com/webcontent/animations/
content/lacoperon.html
•http://highered.mcgrawhill.com/sites/0072556781/student_view0/chap
ter12/animation_quiz_4.html
•Animation at
http://www.dnaftb.org/33/animation.html
•The review problem is at
http://www.dnaftb.org/33/problem.html
Concept 34 - Genes can be moved between
species.
• The genetic code is universal.
• The polymerases of one organism can
accurately transcribe a gene from another
organism.
• For example, different species of bacteria
obtain antibiotic resistance genes by
exchanging small chromosomes called
plasmids.
• 1970s - researchers used this type of
gene exchange to move a "recombinant"
DNA molecule between two different
species.
• 1980s, other scientists adapted the
technique and spliced a human gene
into E. coli to make recombinant human
insulin and growth hormone.
• Recombinant DNA technology — genetic
engineering — lets us see how genes work.
• In cases where it is impractical to test gene
function using animal models, genes can first
be expressed in bacteria or cell cultures.
• Similarly, the phenotypes of gene mutations
and the efficacy of drugs and other agents can
be tested using recombinant systems.
Cohen and Boyer's recombinant DNA
technique "created" the biotech
industry. In 1974, the technique was
submitted for patenting, and in 1976,
the first biotech company, Genentech
Inc., was established based on
recombinant DNA technology.
•Animation and quiz
•http://highered.mcgrawhill.com/sites/0072995246/student_view0/chap
ter4/early_genetic_engineering_experiment.ht
ml
•Animation at
http://www.dnaftb.org/34/animation.html
•The review problem is at
http://www.dnaftb.org/34/problem.html
Concept 35 - DNA responds to signals from
outside the cell.
• Growth and development require that cells
communicate with each other and react to
signals that come from other parts of the
body.
• Chemicals, eg. hormones released by various
glands travel throughout the body to
stimulate the growth of certain cell types.
• Cells capable of being stimulated by a
particular hormone possess a specific
receptor anchored in the cell membrane.
• The binding of a hormone to its receptor
initiates a series of molecular
transformations, called signal
transduction, that relay the growth
signal through the cell.
First, the receptor transduces the
signal through the cell membrane to
the internal membrane surface, where
it activates protein "messengers."
These messengers are part of and
initiate a cascade of chemical
reactions, often involving the addition
of phosphate groups.
This cascade signal passes through the
cytoplasm and into the nucleus.
In the final step of signal transduction,
DNA binding proteins attach to
regulatory sequences and start DNA
replication or transcription.
•Animation at
http://www.dnaftb.org/
35/animation.html
•The review problem is
at
http://www.dnaftb.org/
35/problem.html
Concept 36 - Different genes are active in
different kinds of cells.
Most living things are composed of different
kinds of cells specialized to perform different
functions. A liver cell, for example, does not
have the same biochemical duties as a nerve cell.
Yet every cell of an organism has the same set of
genetic instructions, so how can different types
of cells have such different structures and
biochemical functions?
Since biochemical function is
determined largely by specific
enzymes (proteins), different sets of
genes must be turned on and off in the
various cell types. This is how cells
differentiate.
This notion of cell-specific expression of genes is
upheld by hybridization experiments that can
identify the unique mRNAs in a cell type. More
recently, DNA arrays and gene chips offer the
opportunity to rapidly screen all gene activity of
an organism. Co-expression of genes in response
to external factors can thus be explored and
tested.
•Animation at
http://www.dnaftb.org/36/ani
mation.html
•The review problem is at
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lem.html
Other animations and quizzes
https://highered.mcgrawhill.com/sites/0072995246/student_vi
ew0/chapter24/microarrays.html
https://highered.mcgrawhill.com/sites/0072995246/student_vi
ew0/chapter24/using_a_dna_microarr
ay.html
Concept 37 - Master genes control basic body
plans.
The development of an organism — from a
fertilized egg, through embryonic and juvenile
stages, to adulthood — requires the coordinated
expression of sets of genes at the proper times
and in the proper places.
Studies of several bizarre mutations in the
fruitfly, Drosophila, provided keys to
understanding the molecular basis of large-scale
developmental plans. Early embryonic genes
express proteins that set up the orientation and
define the body segments of the fly embryo.
Then "homeotic" genes act on the segments to
make the body parts distinct to each segment.
Sequence analysis showed that homeotic genes
from Drosophila and vertebrate animals share a
180-nucleotide region, called the homeobox.
These homeobox proteins have structures highly
similar to the regions of regulatory proteins that
bind to DNA promoters and enhancers. Thus, a
homeotic protein elicits coordinated expression
when the protein binds to a specific promoter or
enhancer sequence shared by a number of
genes involved in the development of body
region or segment.
•Animation at
http://www.dnaftb.org/3
7/animation.html
•The review problem is at
http://www.dnaftb.org/3
7/problem.html
Concept 38 - Development balances cell growth
and death.
Growth results from the reproduction of new
cells from pre-existing ones, by the process of
cell division (mitosis). Once a tissue or organ
reaches an appropriate size, mitosis slows and
cells enter a resting phase.
This cell cycle of growth and rest is controlled by
"checkpoint" molecules first characterized in the
1980s and 1990s in yeast, and then in other
eukaryotes.
Remarkably, normal development requires that
some healthy cells be eliminated, killed, by a
process called "apoptosis." Initial clues about
the nature of apoptosis came from detailed
studies of the roundworm Caenorhabditis
elegans, in which development of each of the
959 cells in the adult can be traced from the
fertilized egg.
Analysis of cell "fates" showed that specific cells
are programmed to die at specific times during
embryonic development. Disruptions in the
program lead to an overabundance of cells — a
hallmark of cancer.
•Animation at
http://www.dnaftb.org/38/animation.html
•The review problem is at
http://www.dnaftb.org/38/problem.html
Concept 39 - A genome is an entire set of genes.
Each organism has a defining set of
chromosomes that contain all of its genetic
information. The human genome, for example,
is the set of genetic information encoded in 46
chromosomes found in the nucleus of each cell.
The chromosomes are organized into 23 pairs —
one chromosome of each pair is inherited from
the mother and one from the father. One pair of
chromosomes — X and Y — determine sex; the
other 22 pairs are called autosomes.
So, the human genome is made up of a set of
very long DNA molecules, one corresponding to
each chromosome. The object of the Human
Genome Project was to determine the entire
nucleotide sequence of each of these DNA
molecules — and the location and identity of all
the estimated 35, 000 genes.
It was found that the human genome contains
approximately 20,000 protein-coding genes,
significantly fewer than had been anticipated.
Sequencing the human genome has relied
mainly on automated machines that sequence
the DNA and computer programs that search
and identify genes. A "working draft" DNA
sequence of the human genome was completed
in June 2000. Initial analyses of this working
draft were published in February 2001.
Protein-coding sequences account for only a
very small fraction of the genome
(approximately 1.5%), and the rest is associated
with non-coding RNA molecules, regulatory DNA
sequences, LINEs, SINEs, introns, and sequences
for which as yet no function has been found.
•Animation at
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•The review problem is at
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Concept 40 - Living things share common genes.
All living organisms store genetic information
using the same molecules — DNA and RNA.
Written in the genetic code of these molecules is
compelling evidence of the shared ancestry of
all living things. Evolution of higher life forms
requires the development of new genes to
support different body plans and types of
nutrition. Even so, complex organisms retain
many genes that govern core metabolic
functions carried over from their primitive past.
Genes are maintained over an organism's
evolution, however, genes can also be
exchanged or "stolen" from other organisms.
Bacteria can exchange plasmids carrying
antibiotic resistance genes through conjugation,
and viruses can insert their genes into host cells.
Some mammalian genes have also been
adopted by viruses and later passed onto other
mammalian hosts.
Regardless of how an organism gets and retains
a gene, regions essential for the correct function
of the protein are always conserved. Some
mutations can accumulate in non-essential
regions; these mutations are an overall history
of the evolutionary life of a gene.
•Animation at
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•The review problem is at
http://www.dnaftb.org/40/problem.html
Concept 41 - DNA is only the beginning for
understanding the human genome.
Although DNA transmits genetic information
through time, it basically has a passive role.
Proteins encoded by DNA actually carry out the
myriad cellular reactions that constitute "life."
Now that the Human Genome Project has
provided us with a catalog of tens of thousands
of genes, we are left with the question: "What
do proteins made by these genes actually do?"
Scientists have always looked to mutant
organisms to provide clues about protein
function. Now, specific mutants can be created
at will by inserting an altered or non-functioning
copy of a gene back into a living organism, then
looking for changes in behavior or development.
Since mice breed quickly and share about 99%
of their genes with humans, they have become
the animal model of choice for large-scale
functional studies. However, doing a single
transgenic experiment is several orders of
magnitude more difficult than sequencing the
gene itself. The real work of understanding the
human genome still lies ahead.
•Animation at
http://www.dnaftb.org/41/animation.html
•The review problem is at
http://www.dnaftb.org/41/problem.html