I said that epigenetics modifications work both ways.  For
better or for worse, our epigenome is impacted by the
environment.  This could be a positive force, for example if we
eat properly, or it could be a negative force.

According to Dr. Kim Lyerly, M.D., Director of the Duke
Comprehensive Cancer Centre, exposure to pesticides, toxins, and
synthetic material can methylate genes in adulthood and cause
diseases such as asthma and cancer, both of which are much higher
today than they were decades ago.  Pesticides absorbed by the
mother and passed on to the fetus might remain dormant in the
individual only to cause cancer 10, 20 or 50 years later.

According to Dr. William Schlesinger, Ph.D., Dean of the
Nicholas School of the Environment and Earth Sciences at Duke,
even the lowest detectable limits of a chemical can have grave
consequences if ingested by a living organism.

Dr. David Schwartz, Ph.D., the Director of the “National
Institute of Environmental Health Sciences” explains how
epigenetics and our own well-being tie in with the environment.
“Epigenetics represents a huge opportunity to study an
alternative pathway that explains why individuals respond
differently to environmental cues.  This field provides the
missing link between the environment and the development of
diseases that goes beyond many of the subtle changes in DNA that
explain only a fraction of the diseases humans develop.”

It is becoming increasingly clear to the scientific
community that an extra bit of vitamin, a brief exposure to a
toxin, a settled, happy, and interesting life, and even an extra
dose of parental love can affect the epigenome and impact on the
person for life.

NSAIDs

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) such as
Aspirin work by inhibiting Cyclooxygenase Enzymes (COX1 and COX2)
that catalyze formation of prostaglandins from Arachidonic Acid.
They are used to relieve pain, reduce fever and inflammation,
thinning blood, and slowing the progression of some type of
metastatic growth.  Up till now, the molecular basis of action of
NSAIDs was not fully understood.  Now, however, we can explain
the compounds’ ability to enhance anti-cancer treatments directed
against some types of tumors.

In the most recent issue of Experimental Biology and
Medicine, Dr. Wen-Chun Hung and his team report that one NSAID
known as NS398 up-regulates several genes known to be involved
in negative regulation of cell invasion.  NS398 works by
promoting demethylation of these genes resulting in activation of
their gene expression and subsequent inhibition of cell invasion.

This finding may open a treasure chest:  New treatments for
some cancers that are known to have pro-apoptotic genes
specifically inactivated by methylation.  (Pro-apoptotic genes
put a stop to unwanted cell proliferation and therefore tumors.
If they are inactivated by methylation, they can no longer do
their work; NS398 – and hopefully other compounds in the future -
reverse the process by promoting the demethylation of these
genes).

Sources

1) McGill Reporter
McGill blazes epigenetics trail
Freeing ourselves from genetic destiny
Neale McDevitt
www.mcgill.ca/reporter/38/16/genes/

2) Science Daily (October 27, 2005)
Duke University Medical Centre
“Epigenetics” Means What We Eat, How We Live and Love, Alters How
Our Genes Behave
www.sciencedaily.com/releases/2005/10/051026090636.htm

3) DNA Is Not Destiny
The new science of epigenetics rewrites the rules of diseases,
heredity, and identity
by Ethan Watters
published online November 22, 2006
http://discovermagazine.com/2006/nov/cover

4) Epigenetics and NSAIDs
by Kevin Ahern
March 31, 2008
www.genengnews.com/blog/item.aspx?id=377

It’s a simple proposition.

We eat in moderation and properly (plenty of fruits and
vegetables, little meat, and we make sure we consume adequate
servings of the 4 groups of food recommended by Health Canada).
We exercise restraint when drinking.  We do not smoke.

Since our ancestors were farmers, or otherwise worked very
hard in a physical sense, we should remember to exercise
adequately, for most of us no longer till the soil or perform
hard physical labor.

If we do so, we remain healthy; if we don’t, we suffer from
ill-health.

What happens in real life?  Most of us spend our summers
barbecuing.  We eat as if a time of starvation was just around
the corner!  We drink to excess.  The nation is littered with gym
memberships which are not used!  It’s from the home to the car to
work and back home.

It saddens me in more ways than one.  We deprive ourselves
of the immediate health benefits, our day-to-day feeling of well-
being.  Nature – through epigenetics – gives us a second chance.
Heart diseases may be rampant in both mom’s and dad’s families.
However, that doesn’t make you a marked man.  You don’t have a
contract on your head!  If you follow a healthy lifestyle, you
can live to a ripe old age.  You can change your genetic destiny.
How?  By following what I said at the beginning of this section,
and by checking regularly with your doctor to make sure your
heart remains healthy.  Healthy living allows your epigenome to
alter your genome.  It’s the ghost in your genes that allows you
to regain control.

Food rich in methyl molecules (e.g. onions, garlic, beets)
can change the behavior of a gene, the methyl groups can either
activates it, or conversely silence the gene.

Epigenetics works both ways, methylated genes can be
demethylated.  And methyl tags that are knocked off can be
regained via nutrients, drugs, and enriching experiences.

There are, however, limits to this process; do not go too
far.  What I am saying is that you should not research and
experiment – in a big way – on your own.  Examples:  Exercise is
great, too much of it can be harmful.  An enriching experience
does not refer to a poker game!  Do not try to find a whole bunch
of methyl-rich food, too much methyl can affect your epigenetics
mechanism.  Put simply:  Use your common sense.  Epigenetics is
still very young.  We still have a lot to learn.

Nature or Nurture?

Nature or nurture?  This is one of the oldest chicken-and-
egg debate humans have indulged in.  Thanks to epigenetics we
finally have an answer.

Dr. Randy Jirtle, Ph.D., a genetic researcher in Duke’s
University has this to say, “We can no longer argue whether genes
or environment has a greater impact on our health and development
because both are inextricably linked.”  He also adds, “Before,
genes predetermined outcomes.  Now everything we do – everything
we eat or smoke – can affect our gene expression and that of
future generations.  Epigenetics introduces the concept of free
will into our idea of genetics.”

Until recently, the structure of an individual epigenome was
thought to be firmly established during early fetal development.
While this is still seen as a critical period, scientists are now
realizing that the epigenome can change in response to the
environment throughout the lifetime of a person.

Having never experimented with drugs, I can only speculate
as to the reasons people start using them and eventually getting
hooked.  Some possibilities:  Under peer pressure, at a young
age, trying a drug(s); escaping an emotionally taxing situation;
or simply boredom.  The brain has 40 to 50 billion neurons, the
number of connections (synapses) between these neurons defy
compilation (we’re probably talking of trillions).  There is
constant firing of neurons, endless chattering.  As long as we
are awake, the brain is incredibly active.  Active doing what?
Well, that’s exactly the point, the brain need to be constantly
“fed.”  What food?  Knowledge, challenges, intelligent activity.
We either keep ourselves meaningfully occupied, or we shush our
brain – with drugs.  But there is a price to pay.

According to recent research, psychoactive drugs can modify
the epigenetic code of our brain cells.  Recent findings throw
some light that might help to explain how transient changes in
the brain (the presence of drugs) result in long-term alterations
to the connections (between neurons) that can ultimately lead to
addiction.

The brain learns by constantly linking events with results
until associative memories are formed.  Drugs that produce a
“high” or a good feeling impact this learning circuit:  It seems
that, in addiction, the reward-related learning system goes into
pathological overdrive leading to compulsion.  Regular drug use
further reinforces the “good” memory and sets the stage for a
vicious circle: the more you use a drug, the more you need it;
the more you need it, the more you consume; and you start anew
with the situation getting progressively worse.

At a physical level, learning promotes the strength of
connections and enhances communications between neurons.  It is
not clear how this happens at the molecular level.  It is
believed that it involves the switching on of genes that control
changes in the structure of the connections.

A number of genes are switched on in brain cells following
consumption of a drug; new research shows that this switch
mechanism involves epigenetics modifications – chemical changes
to either the DNA or the histones.

I will remind the reader that epigenetics changes do not
affect the DNA code itself, but rather, make – or does not make -
the code available for transcribing and eventually synthesizing a
protein.

Depending upon the mode of consumption, genes are impacted
in three ways.  Let’s use cocaine as an example.  Certain genes
are switched on by infrequent (acute) administration of cocaine,
while others are switched on only after chronic use.  Finally,
some are switched on by both.  The gene activated by acute
consumption, get their associated histone H4 proteins acetylated,
while gene switched on by chronic drug use get their associated
H3 proteins acetylated.  Finally, genes that are activated by
both types of drug usage, show H4 acetylation when cocaine is
first used, and then switch to H3 acetylation as the consumption
becomes chronic.  One more point, H3 acetylation persists long
after cocaine withdrawal; this would explain why breaking an
addiction is such a difficult thing.

No doubt you’re reading this difficult and technical part in
the hope that I will tell you that there is on the horizon a
possible cure for addiction.  Is there?  It seems so, although we
are not there yet.

The same genes that are activated by cocaine can also be
switched on by other addictive drugs.  If it turns out that these
other drugs are also acting epigenetically and with long-lasting
effect, then researching how to erase the epigenetics changes in
specific areas of the brain could possibly lead to a treatment of
addiction.

Source

Addiction:  the epigenetic effect
Ruth Williams
September 2006
http://epigenome.eu/en/1,37,0

In 2003, Dr. Moshe Szyf, professor of Pharmacology, McGill
University, and Michael Meaney, Associate Director of Research,
Douglas Hospital, conducted an important experiment.

First they observed that young rats who received a healthy
dose of maternal licking and grooming (the human equivalent of
maternal care) as pups developed into much calmer adults.  Those
rats who were deprived at the onset of this rat-like maternal
affection were decidedly more stressed.  This, needless to say,
is not an earth-shaking discovery.  We have known for a long time
the importance of maternal care, and its lifetime impact on the
individual.

The question raised by Meaney was “why the change in
behavior?”  It seems that the maternal licking stimulate a
chemical change in the glucocortoid receptor in the brain, the
very mechanism that regulates the amount of stress hormone
released by the rat’s adrenal gland.  The less maternal affection
a young rat received, the more stress hormones it produced as an
adult.

Next, Szyf administered methionine, an essential amino acid,
to the brains of the calm rats, this impacted their respective
glucocortoid receptors and they, like their neglected cousins,
became nervous wrecks!

Similarly, the McGill team reduced the levels of the same
hormones in anxious rats by pharmacologically manipulating the
same gene that produces them.  These findings have profound
implications, they suggest that similar interactions could be
used to fight depression, schizophrenia, and other brain
disorders.

Dr. Arturas Petronis M.D., PhD, Head of the Krembil Family
Epigenetics Laboratory at the University of Toronto, throw some
light on a long-standing enigma.  While DNA changes are
permanent, epigenetics modifications are in a state of flux and
generally accumulate over time.  This may explain why bipolar
disorder tends to appear at age 20 – 30 and 45 – 50.  This is due
to major hormonal changes at these ages which may in turn impact
gene regulations … via their epigenetics modifications.

The good news here is that epigenetics disorders can be
reversed making them inviting targets for new drugs.
The Future

Gradually, the evidence is accumulating and it is showing
that many genes, diseases, and environmental substances are part
of the epigenetics equation.  However, we need much more work to
be done in this area before drawing firm conclusions about the
impact of epigenetics on diseases.

Potentially, more research on epigenetics can go a long way
in curing many human diseases.  Yet, investment in this area of
study remains minuscule compared to that devoted to traditional
genetics work.  But there is a light at the end of the tunnel.

In Europe, the Human Epigenome Project was officially
launched in 2003 by the Wellcome Trust Sanger Institute,
Epigenomics AG, and the Centre Nationale de Genotypage.  The
group’s work is on DNA methylation tied to chromosomes 6, 13, 20,
and 22.  They may soon be joined by organizations in Germany and
India where research will be carried out on chromosomes 21 and X.

It’s a beginning.  But the task is enormous.  A Human
Epigenome Project will be far more complex than a Human Genome
Project.  The sooner we start, the better.  Humanity, even in the
21st century, is still affected by many diseases.

Sources

1) Backgrounder:  Epigenetics and Imprinted Genes
www.hopkinsmedicine.org/press/2002/november/epigenetics.htm

2) Epigenetics:  The Science Of Change
www.ehponline.org/members/2006/114-3/focus.html

3) Epigenetics
A new science peels away another layer of the genetic onion
by John McManamy
www.mcmanweb.com/epigenetics.html

4) McGill Reporter
McGill blazes epigenetics trail
Freeing ourselves from genetic destiny
Neale McDevitt
www.mcgill.ca/reporter/38/16/genes/

Inherited diseases until now seemed inevitable.  Cancer,
cardiovascular diseases, or dementia were destined to happen to
you if one or more of these illnesses has been running in your
family for generations.  This so far has been the accepted
wisdom.  But is it true?  No, thanks to epigenetics we can
overcome these curses.  But how can it be accomplished?  While
epigenetics is opening the door to some amazing medicines and
treatments, the solution is decidedly low-tech!  It goes back to
mother’s advice:  Eat your vegetables, eat less meat, do not
smoke, do not drink to excess, take a gym membership, and
generally keep body and mind stimulated.  Your mom didn’t know
it, but in so doing, you are altering your genetic destiny!

For instance, the health benefits of a proper diet and
exercise will actually modify the expression of our DNA, such
monsters as kidney diseases and Alzheimer which are lurking
within our genes can be banished.  Put in a more direct way,
let’s stop looking in the direction of scientific labs, the cure
in many cases depend on what we eat and how active we are.  The
cure in other words is in our hands.

Cancers

Many researchers engaged in epigenetics research are
targeting cancer.  Dr. Peter Jones, Director of the University of
Southern California’s Norris Comprehensive Cancer Centre view the
evidence linking epigenetics processes with cancer as “extremely
compelling.”  The Chief of the Carcinogenesis Division of Japan’s
National Cancer Centre Research Institute, Dr. Toshikazu
Ushijima, points out that epigenetics processes are one of the
five most important factors in the cancer field, and they account
for one-third to one-half of all known genetic modifications.

Under “Imprinting and Diseases” an important point was made.
I am restating it here.

In cancer, some tumor suppressor genes that come from the
mother are turned off in error, and the growth-limiting protein
can no longer be produced.  Along the same line, many oncogenes
(growth-promoting genes) originate with the father.  On occasion,
we can have a double whammy, both sets of genes can malfunction;
if the maternal copy of the oncogene loses its epigenetics marks
and is turned on as well, cell growth gets out of control.

In Johns Hopkins University, research is conducted to
understand the mechanism behind imprinting.  Hopefully, in time,
drugs or treatments will be developed to address the above
epigenetics errors.

Autoimmune Diseases

Malfunctions related to the epigenetics immune system can
occur, and can be reversed.  The research was published in the
November-December 2005 issue of the Journal of Proteome Research
by Nilamadhab Mishra, an Assistant Professor of Rheumatology at
the Wake Forest University School of Medicine, and his
colleagues.

The team has established a specific link between aberrant
histone modifications and mechanisms underlying Lupus-like
symptoms in mice; there is a drug in the research stage,
Trichostatin, that can reverse the abnormalities.  This medicine
appears to reset the aberrant histone changes by correcting
hypoacetylation at two histone sites.

One more example of this type of research.  Dr. Bruce
Richardson, Chief of the Rheumatology Section of the Ann Arbor
Veterans Affairs Medical Centre and a professor at the University
of Michigan Medical School reported that pharmaceuticals such as
the heartdrug Procainamide and the antihypertensive agent
Hydralazine cause Lupus in some people.  He demonstrated that
Lupus-like symptoms in mice exposed to these drugs is linked with
DNA methylation changes and interruption of signalling pathways
similar to those in people.

What is Imprinting?

Imprinted genes do not follow traditional laws of Mendelian
genetics which view inheritance of trait as either dominant or
recessive.  In Mendelian genetics both parental copies have an
equal chance to contribute to the result.  In the case of an
imprinted gene copy, however, the cell uses either the father or
the mother to make the required protein.

Imprinting in genetics is not new.  However, its impact is
gaining more attention as it is linked to more diseases.
Centuries ago, mule breeders in Iraq noted that crossing a male
horse with a female donkey produced a different animal than
breeding a female horse and a male donkey.

Further research on mice in the mid ’80s indicated that
normal development requires genes to be inherited from both
parents.  The research also indicated that the resulting
abnormalities changed depending upon whether the genes were from
the male or the female mouse.

The first naturally occurring example of an imprinted gene
that was discovered is the IGF-2 gene in mice in 1991; presently
about 50 imprinted genes have been identified in mice and humans.

Importance of Imprinting

It’s a bit of a mystery as to why imprinting evolved.  One
theory is that imprinting represents a genetic “battle of the
sexes,” since many imprinted genes play a role in embryonic
growth.

Simply stated, the male has a stake in growth and paternally
expressed genes usually stimulate growth; on the other hand,
maternally expressed imprinted genes (for which the copy from the
female is always used) suppress growth.  So what is at stake
here?  The male wants to pass on his genes, continuity is the
issue.  The female, however, is more interested in maintaining
her own health (in a biological sense) and therefore she opposes
the male genes and limit the size of the fetus.

Imprinting and Diseases

If we continue with the above theory, we find that imprinted
genes may have something to do with the development of cancer,
and other conditions in which tissue growth are abnormal.
Imprinted genes in which the mother’s copy is turned on usually
suppress growth, while the father’s copy usually stimulates
growth.

In cancer, some tumor suppressor genes that come from the
mother are turned off in error, and the growth-limiting protein
can no longer be synthesized.  Likewise, many oncogenes (growth-
promoting genes) originate with the father.  Sometimes, both sets
of genes can malfunction; if the maternal copy of the oncogene
loses its epigenetic marks and is turned on as well, cell growth
gets out of control.

There are birth defects collectively known as Beckwith-
Wiedemann syndrome; in this case, abnormal epigenetics leads to
abnormal growth of tissues, enlargement of abdominal organs, low
blood sugar at birth, and cancer.  Similarly, in the imprinting
disorder known as Prader-Willi syndrome, abnormal epigenetics
causes short stature, mental retardation, and other problems.

Causes of Imprinting Errors

When DNA copies itself, mutations (errors in copying) can
result, and the daughter copy will be somewhat different.  By the
same token, changes in a cell’s epigenetics can happen.  While
mutations are fairly well understood, causes of epigenetics
mistakes are less clear.  Scientists are aware that epigenetics
changes can be caused by environmental changes, but the details
are still hazy.

Imprinting Research

It’s important to carry out more research in this area.  For
example, what marks distinguish maternal and paternal gene
copies, and are they the same for all imprinted genes?  Can we
control the process and reestablish normal control to cells in
tumors?

Hopkins researchers created a mouse model in which the
paternal and maternal gene copies are easily distinguished; this
will help pierce the many mysteries connected with imprinting.
Equivalent experiments with humans are not currently permitted.

Source

Backgrounder:  Epigenetics and Imprinted Genes
www.hopkinsmedicine.org/press/2002/november/epigenetics.htm

One in every 250 births will result in IT.  They start and
end their lives with the same genetic package, but as they grow,
differences in their environment will alter their appearance and
behavior.

If one member of an IT set committed a crime and, in error,
left samples (hair, blood, etc.) which can be used to determine
his DNA, it would still be impossible to determine the culprit,
their DNA being the same.  However, closer inspection at the
molecular level will reveal significant differences, and thus
will help identify who of the two is guilty.  You see, they may
be identical genetically, but not epigenetically.  Some genes
might be active in one twin but not the other.

Why the difference in gene activity (or inactivity)?
Biochemical fine tuning of the genome will determine which genes
are expressed or silenced.  This point has already been outlined
under Methylation.  I have also discussed the impact of Histones.
The conclusion here is that IT are not really identical.  They
start that way, but then diverge.  But the time they reach old
age, they are really very different individuals.

One more important issue:  IT are not fated to suffer from
the same genetically inherited disease(s).  Dr. Arturas Petronis
M.D., PhD, head of the Krembil Family Epigenetics laboratory at
the University of Toronto provides us with an example.  There is
a high occurrence of IT with Bipolar Disorder, but Dr. Petronis
explains that epigenetics may account for the 30 – 70% of cases
where only one twin has the illness.  While IT share the same
genome, their epigenome differs.  Moreover, whereas DNA variation
are permanent, epigenetics modifications are in a state of flux
and generally accumulate over time.  This may elucidate another
mystery, namely why Bipolar Disorder tends to appear at ages 20 -
30 and 45 – 50.  This is due to the major hormonal changes at
these ages which may in turn impact genes regulations … via
their epigenetic modifications.

The good news here is that epigenetic disorders can be
reversed making them inviting targets for new drugs.

Sources

1) Epigenetics
Science in School
How epigenetics shapes life
www.scienceinschool.org/2006/issue2/epigenetics/

2) Epigenetics
A new science peels away another layer of the genetic onion
by John McManamy
www.mcmanweb.com/epigenetics.html

There are 20 AA.  They are in alphabetical order:

Alanine.  Arginine*.  Asparagine.  Aspartic Acid.  Cysteine.
Glutamic Acid.  Glutamine.  Glycine.  Histidine*.  Isoleucine*.
Leucine*.  Lysine*.  Methionine*.  Phenylalanine*.  Proline.
Serine.  Threonine*.  Tryptophan*.  Tyrosine.  Valine*.

The atoms in AA are:  hydrogen, carbon, nitrogen, oxygen,
and sulfur.

We need to understand AA structure and properties to be able
to understand protein structure and properties.  Even a small
relatively simple protein is made out and depend on the AA which
comprises it.

Humans can produce 10 of the 20 AA.  The others must be
present in our diet.  Failure to obtain enough of even 1 of the
10 essential AA (those we cannot make) will mean that the body
will break its own tissues to obtain that one AA!

Unlike fat and starch, humans do not store excess AA for
later use;  AA must be part of our daily diet.  [Compare with
glucose which is stored in the liver and muscles (in the form of
glycogen).  It would be handy if the same applied to AA!].

The essential AA are indicated by an * in the above list.
These AA must be in your diet.

Plants, of course, must be able to produce all the AA.
Humans though lacks the enzymes needed to synthesize all 20 AA.

Sources

1) Arizona State University
Center for Bioenergy & Photosynthesis
DNA, RNA and Protein Synthesis
http://photoscience.la.asu.edu/photosyn/courses/bio_343/lecture/DNA-RNA.html

2) University of Arizona
Department of Biochemistry and Molecular Biophysics
The Biology Project
The Chemistry of Amino Acids
September 30, 2003
www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html

3) University of Texas Medical Branch
Cell Biology Graduate Program
What happens at the site of the ribosome?
http://cellbio.utmb.edu/CELLBIO/ribosome.htm

4) Biology
John W. Kimball
Tufts University
Addison-Wesley Publishing Company
April 1975

Ribosomes are roughly-spherical bodies that are contained
within the cell.  They are very small and can be seen only under
the electron microscope.  They are formed from two subunits, one
being larger than the other.

Ribosomes are the factory where a given protein is
manufactured.  Put in a simple way:  the mRNA brings the
instructions needed to synthesize the protein; the Amino Acids
(AA) required for the protein are carried to the site by the
tRNA; finally, as already mentioned, rRNA is part of the
machinery (and part of the ribosome itself) that manufacture the
protein.

Protein Synthesis

Physically you are made out of countless proteins.  Your
tissues, your bones, your blood, your organs, your enzymes, your
hormones, even your thoughts and memories are presumably
proteins.  The majority of proteins (within the same gender) are
similar.  Some proteins, however, are peculiar to a given
individual; indeed no two individuals have the exact same
proteins, not even identical twins!  (Because of the impact of
the environment, and its effect on the epigenetic code, identical
twins are not 100% identical.  This will be discussed in the
section on identical twins).

As discussed, proteins are synthesized in the ribosome of
the cell.  The assembly, following the blueprint provided by the
DNA and transported to the ribosome by the mRNA involves:

1) Controlled formation of a peptide bond between two AA.
This operation is repeated many times as each AA in turn is added
to the polypeptide chain.

Remember that at the end of the section on RNA I mentioned
that the DNA instructions include promoters and terminators
sequences.  These sequences in effect indicate to the ribosome
where to start and at what point to stop.  At the end of the
process, the manufactured protein is released to be used by the
body.  This operation is repeated million of times with a balance
maintained throughout the whole organism!  One question remains,
however.  How does the cell codes for the various AA?

2) The code

A great deal of work was carried out to crack the code.
Ultimately, the research was done in test tubes!  When many
biologists expressed doubt as to whether such a system really
operated in living organisms, more work was done on viruses with
a single strand of RNA.  To make a long story short, the validity
of the code was eventually verified.  If interested, you can
research and read further the fascinating story behind one of the
most extraordinary achievements of the 20th century!

So what is the code?

Remember that the four bases for RNA are: A,C,G,U.  Also
keep in mind that there are 20 AA and that we need different
codes for each one.

One base is insufficient to code a single AA.  Pairs of
bases could be arranged in 16 different ways (AA, UU, UA, etc.).
But we are still short since we have 20 AA.  Triplets of bases,
on the other hand, can be arranged in 64 different ways, more
than enough to code for 20 AA.  Because of this coding
relationship, a triplet of bases is called a codon.  To add to
the complexity, each AA is coded by one or more (up to six)
codons.

Three of the 64 possible codons (UAA, UAG & UGA) have not
been found to code for any AA.  They act as chain terminators.
When the ribosome reaches them, the polypeptide chain is
completed and is released to carry out its function in the cell.

Some examples of the code together with the corresponding
AA:

AUG for Methionine; UCG for Tryptophan; UUU & UUC for
phenylalanine; UUA & UUG for Leucine; CUU, CUC, CUA & CUG for
Leucine; GGU, GGC, GGA & GGG for Glycine.

Note the following:

1 to 4 codons codes for the above AA.

Leucine is coded by 2 or 4 codons (in most cases, several
codons code for a single AA, and one codon may be “preferred” by
one organism, another by a different organism).

I said that three codons (UAA, UAG & UGA) act as chain
terminators; what indicates the starting point?  AUG is used for
that purpose when it is at the beginning; when it is within the
message being decoded it is used (as shown above) to code for
Methionine.

Most of the codons have been assigned as a result of studies
with E.Coli; there is evidence that the code is the same for all
organisms.

DNA (Deoxyribonucleic Acid)

A DNA molecule is very long and very thin, yet it fits
inside a much smaller (cell) nucleus and is folded up in the
chromosome in a very precise manner.  DNA is a linear polymer
made out of four different building blocks, the nucleotides.  The
sequence of the nucleotides is in effect the genetic information
that will allow the cell to carry out its work.  Each nucleotide
is composed of three parts:  The first part is a nitrogenous base
known as Purine [Adenine (A) and Guanine (G)] or Pyrimidine
[Cytosine (C) and Thymine (T)]; the second part is a Sugar,
Deoxyribose; the final part is a Phosphate Group.  The
nitrogenous base provide any given nucleotide with its identity
and it is referred to by its base, i.e. A,C,G,T.  (This in effect
was the information provided by The Human Genome Project, an
endless number of A,C,G,T; billions of them!)  One DNA strand can
be up to several hundred million nucleotides in length.  Note
that T match with A and C with G.

Picture a technical setting with technicians assembling the
components of an intricate device.  They are guided in their work
by an instruction manual, it’s their bible.  This is in fact the
role of DNA inside the cell; it provides the cell with the
instruction it needs to do its work.  However, the “technician”
is RNA (Ribonucleic Acid); it translates the information into a
medium that can be used directly by the cell.

Note that all cells for a given individual contain the same
genetic information.  However, for any given organ, only certain
genes are expressed, the rest are silenced (they are inactive).
For example liver cells will only produce the proteins allocated
to the liver, not those of the heart or the brain!  This gene
silencing process has been discussed in the Overview.

RNA (Ribonucleic Acid)

RNA differs from DNA in that it includes in the second
position of the Ribose Ring a Hydroxy (-OH) group.  Put in a
simpler way, Thymine (T) does not occur in RNA and is replaced by
Uracil (U).  Thus the coding for RNA is A,C,G,U.

RNA has three functions: a) It serves as the messenger that
tell the cell (the ribosomes) what proteins to make [Messenger
RNA (mRNA)]; b) It’s part of the structure of the ribosome, the
protein/RNA complex that synthesizes proteins based on the coding
carried over by the mRNA [Ribosomal RNA (rRNA)]; and c) it
obtains the Amino Acids (AA) (the constituents of the proteins)
needed by the ribosome [since it transfers to the cell the needed
AA, it is called Transfer RNA (tRNA)].

Looking upon it in a more simplified way, the DNA provides
the mRNA with a “shopping list” of AA and instructions as to how
to put them together (like in a recipe where you first list the
needed ingredients, followed by the required methodology to cook
this particular dish).  The rRNA does the “cooking” after the
tRNA had obtained and transferred to the cell the needed AA.

The process gets too technical after that and goes beyond
the scope of this simplified narrative.  I am, however, including
one important point.

The required genetic information is transcribed from the DNA
to the mRNA.  This happens at a specific site on the DNA called a
promoter.  Each gene has its own promoter(s).  Transcription ends
at a terminator sequence on the DNA.  The transcripts can be
between 300 to 50,000 nucleotides long and contain the
instructions needed to make the protein in question.  Generally,
the transcripts need to be processed before they can be used as a
blueprint for a protein.  This is done by removing intervening
sequences (introns) in the genes.