Keith Hudson said:
It is no longer Nature versus Nurture. Each of us is a product of
Nature and Nurture. Thus, each of us, by our own individual decisions can to
some extent influence the way our genes behave. For example, it is possible for
an individual to avoid an illness, such as a form of cancer, to which certain of
his genes might have made him vulnerable by being sensible about his behaviour.
Avoiding excessive sunlight is one obvious example.
At last, the third way. How wonderful to be finding your way
out of the X/O duality trap of Western Thought. Now, how about doing
the same for economics and political Socialist vs. Capitalist thought or is that
too much to ask?
REH
----- Original Message -----
Sent: Wednesday, October 08, 2003 4:07
AM
Subject: [Futurework] A truce in the
Nature versus Nurture argument
Yesterday's article in the New York Times by
Sandra Blakesee and pointed out to us by Selma was an attempt to describe some
of the latest thinking and research about genetics. I do not use the word
"attempt" in a pejorative sense because this new area -- now termed
'epigenetics' -- is mind-bendingly complex and Sandra Blakesee's article was a
brave essay for ordinary readers. This is important, because epigenetics ought
to call a truce in the nature-nurture controversy in the coming years.
Two terms, new to most people, are useful in this discussion. One is
'nucleosome'. This simply means 'a body that is found in the nucleus (of a
cell)'. There are uncountable millions of them in a nucleus. Each nucleosome
consists of a spherical ball consisting of a compressed bundle of eight
protein molecules called 'histones' with their ends dangling outside. It is
these dangling ends, waving in the breeze, as it were, which are the crux of
the matter.
The immensely long, twin-coiled helix of our DNA,
containing our genes, is normally totally insulated -- and rendered inactive
-- by being closely covered by millions of nucleosome balls which actually
cause the DNA to coil further and further in an amazingly beautiful way until
it is very compact. But the tails of the histones which constitute the
nucleosomes dangle untidingly into the 'soup' of the rest of the nucleus so
that the whole DNA structure (the chromosome) looks like a hairy worm.
The histones have two remarkable properties. Firstly, their tails are
extremely chemically sensitive to what is going on around them in the nucleus
soup. Secondly, depending on these effects (such as the 'methylation' process
mentioned below) the histone tails can then instruct the nucleosome to which
it belongs whether to relax its grip on the DNA and allow some of its interior
genes to become exposed to the surrounding soup and 'express'
themselves.
The DNA genes express themselves by making molecules called
messenger RNA which then race through holes in the nucleus wall and into the
rest of the cell where they instruct small chemical machines called ribosomes
to make the proteins that that particular cell needs in order to carry out its
main function -- whether it is a liver cell or a muscle cell or
whatever.
The important point is this that until very recently this was
thought to be a one-way process. Thus, 'genetics' used to say: "each of us is
an inevitable product of the genes with which we were endowed at the point of
fertilisation". What has happened recently is that 'epigenetics' is now
saying: "the _expression_ of our genes can be modified to some extent by the
environment outside the DNA".
It is no longer Nature versus Nurture.
Each of us is a product of Nature and Nurture. Thus, each of us, by our
own individual decisions can to some extent influence the way our genes
behave. For example, it is possible for an individual to avoid an illness,
such as a form of cancer, to which certain of his genes might have made him
vulnerable by being sensible about his behaviour. Avoiding excessive sunlight
is one obvious example.
On the other hand, the nucleosomes with their
all-important dangling histone tails don't appear out of nowhere in the cell
nucleus. They are themselves made on the instructions of some of the genes
that they control! Thus our total performance is still limited by the stock of
genes each of us inherits. Each of us only has a small amount of freedom to
influence the way our genes behave.
But the feedback from the
environment via the histone tails via the nucleosomes to the _expression_ of our
genes gives a huge amount of extra freedom to the evolution of species over
the longer term. The environment helps to consolidate the importance (or not)
of a new gene that appears accidentally by mutation. New genes arise
accidentally but whether they are useful and are thus reproduced in our
progeny depends on the environment.
Thus, there was 'something' about
the nature of our predecessors' hunter-gatherer environment which encouraged
the activity of some genes. Among these are the genes that are responsible for
the development of the frontal lobes of our brains. Each new mutation that
caused yet more brain cells to be instituted in this area was an accident, but
it was consolidated by some of the particular features of the hunter-gatherer
environment. Over a relatively short period in evolutionary terms (a few
million years), our frontal lobes grew enormously and made us so very
different from our close primate cousins such as the chimpanzee and the
gorilla who stayed within the tropical forests.
Our present environment
is completely different from our hunter-gatherer times but it, too, will be
having its feedback effects on our DNA. Quite what they'll be in due course is
quite another matter.
Keith Hudson
<<<< A PREGNANT MOTHER'S DIET MAY TURN THE GENES
AROUND
Sandra Blakeslee
With the help of some fat yellow mice,
scientists have discovered exactly how a mother's diet can permanently alter
the functioning of genes in her offspring without changing the genes
themselves.
The unusual strain of mouse carries a kind of trigger near
the gene that determines not only the color of its coat but also its
predisposition to obesity, diabetes and cancer. When pregnant mice were fed
extra vitamins and supplements, the supplements interacted with the trigger in
the fetal mice and shut down the gene. As a result, obese yellow mothers gave
birth to standard brown baby mice that grew up lean and
healthy.
Scientists have long known that what pregnant mothers eat
whether they are mice, fruit flies or humans can profoundly affect the
susceptibility of their offspring to disease. But until now they have not
understood why, said Dr. Randy Jirtle, a professor of radiation oncology at
Duke and senior investigator of the study, which was reported in the Aug. 1
issue of Molecular and Cellular Biology.
The research is a milestone in
the relatively new science of epigenetics, the study of how environmental
factors like diet, stress and maternal nutrition can change gene function
without altering the DNA sequence in any way.
Such factors have been
shown to play a role in cancer, stroke, diabetes, schizophrenia, manic
depression and other diseases as well as in shaping behavioral traits in
offspring.
Most geneticists are focusing on sequences of genes in
trying to understand which gene goes with which illness or behavior, said Dr.
Thomas Insel, director of the National Institute of Mental Health. "But these
epigenetic effects could turn out to be much more important. The field is
revolutionary," he said, "and humbling."
Epigenetics may indeed hold
answers to many mysteries that classical genetic approaches have been unable
to solve, said Dr. Arturas Petronis, an associate professor of psychiatry at
the Center for Addiction and Mental Health at the University of
Toronto.
For example, why does one identical twin develop schizophrenia
and not the other? Why do certain disease genes seem to affect or "penetrate"
some people more than others? Why do complex diseases like autism turn up in
more boys than girls?
For answers, epigeneticists are looking at
biological mechanisms other than mutation that affect how genes function. One,
called methylation, acts like a gas pedal or brake. It can turn gene
_expression_ up or down, on or off, depending on how much of it is around and
what part of the genetic machinery it affects.
During methylation, a
quartet of atoms called a methyl group attaches to a gene at a specific point
and induces changes in the way the gene is expressed.
The process
often inactivates genes not needed by a cell. The genes on one of the two X
chromosomes in each female cell are silenced by methylation.
Methyl
groups and other small molecules may sometimes attach to certain spots on
chromosomes, helping to relax tightly coiled strands of DNA so that genes can
be expressed.
Sometimes the coils are made tighter so that active genes
are inactivated.
Methyl groups also inactivate remnants of past viral
infections, called transposons. Forty percent of the human genome is made up
of parasitic transposons.
Finally, methyl groups play a critical role
in controlling genes involved in prenatal and postnatal development, including
some 80 genes inherited from only one parent. Because these so-called
imprinted genes must be methylated to function, they are vulnerable to diet
and other environmental factors.
When a sperm and egg meet to form an
embryo, each has a different pattern of methylated genes. The patterns are not
passed on as genes are, but in a chemical battle of the sexes some of the egg
and sperm patterns do seem to be inherited. In general, the egg seems to have
the upper hand.
"We're compounds, mosaics of epigenetic patterns and
gene sequences," said Dr. Arthur Beaudet, chairman of the molecular and human
genetics department at Baylor College of Medicine in Houston. While DNA
sequences are commonly compared to a text of written letters, he said,
epigenetics is like the formatting in a word processing program.
Though the primary letters do not vary, the font can be large or
small, Times Roman or Arial, italicized, bold, upper case, lower case,
underlined or shadowed. They can be any color of the
rainbow.
Methylation is nature's way of allowing environmental factors
to tweak gene _expression_ without making permanent mutations, Dr. Jirtle
said.
Fleeting exposure to anything that influences methylation
patterns during development can change the animal or person for a lifetime.
Methyl groups are entirely derived from the foods people eat. And the effect
may be good or bad. Maternal diet during pregnancy is consequently very
important, but in ways that are not yet fully understood.
For his
experiment, Dr. Jirtle chose a mouse that happens to have a transposon right
next to the gene that codes for coat color. The transposon induces the gene to
overproduce a protein that turns the mice pure yellow or mottled yellow and
brown. The protein also blocks a feeding control center in the brain. Yellow
mice therefore overeat and tend to develop diabetes and cancer.
To see
if extra methylation would affect the mice, the researchers fed the animals a
rich supply of methyl groups in supplements of vitamin B12, folic acid,
choline and betaine from sugar beets just before they got pregnant and through
the time of weaning their pups. The methyl groups silenced the transposon, Dr.
Jirtle said, which in turn affected the adjacent coat color gene. The babies,
born a normal brownish color, had an inherited predisposition to obesity,
diabetes and cancer negated by maternal diet.
Unfortunately the
scientists do not know which nutrient or combination of nutrients silence the
genes, but noted that it did not take much. The animals were fed only three
times as much of the supplements as found in a normal diet.
"If you
looked at the mouse as a black box, you could say that adding these
methyl-rich supplements to our diets might reduce our risk of obesity and
cancer," Dr. Jirtle said. But, he added, there is strong reason for
caution.
The positions of transposons in the human genome are
completely different from the mouse pattern. Good maps of transposons in the
human genome need to be made, he said. For that reason, it may be time to
reassess the way the American diet is fortified with supplements, said Dr. Rob
Waterland, a research fellow in Dr. Jirtle's lab and an expert on nutrition
and epigenetics.
More than a decade ago, for example, epidemiological
studies showed that some women who ate diets low in folic acid ran a higher
risk of having babies with abnormalities in the spinal cord and brain, called
neural tube defects.
To reduce this risk, folic acid was added to
grains eaten by all Americans, and the incidence of neural tube defects fell
substantially. But while there is no evidence that extra folic acid is harmful
to the millions of people who eat fortified grains regularly, Dr. Waterland
said, there is also no evidence that it is innocuous.
The worry is
that excess folic acid may play a role in disorders like obesity or autism,
which are on the rise, he said. Researchers are just beginning to study the
question.
Epidemiological evidence shows that undernutrition and
overnutrition in critical stages of development can lead to health problems in
second and third generations, Dr. Waterland said.
A Dutch famine near
the end of World War II led to an increased incidence of schizophrenia in
adults who had been food-deprived during the first trimester of their mothers'
pregnancy. Malnourishment among pregnant women in the South during the Civil
War and the Depression has been proposed as an explanation for the high
incidence of stroke among subsequent generations.
And the modern
American diet, so full of fats and sugars, could be exerting epigenetic
effects on future generations, positive or negative. Abnormal methylation
patterns are a hallmark of most cancers, including colon, lung, prostate and
breast cancer, said Dr. Peter Laird, an associate professor of biochemistry
and molecular biology at the University of Southern California School of
Medicine.
The anticancer properties attributed to many foods can be
linked to nutrients, he said, as well as to the distinct methylation patterns
of people who eat those foods. A number of drugs that inhibit methylation are
now being tested as cancer treatments. Psychiatrists are also getting
interested in the role of epigenetic factors in diseases like schizophrenia,
Dr. Petronis said.
Methylation that occurs after birth may also shape
such behavioral traits as fearfulness and confidence, said Dr. Michael Meaney,
a professor of medicine and the director of the program for the study of
behavior, genes and environment at McGill University in Montreal.
For
reasons that are not well understood, methylation patterns are absent from
very specific regions of the rat genome before birth. Twelve hours after rats
are born, a new methylation pattern is formed. The mother rat then starts
licking her pups. The first week is a critical period, Dr. Meaney said. Pups
that are licked show decreased methylation patterns in an area of the brain
that helps them handle stress. Faced with challenges later in life, they tend
to be more confident and less fearful.
"We think licking affects a
methylation enzyme that is ready and waiting for mother to start licking," Dr.
Meaney said. In perilous times, mothers may be able to set the stress
reactivity of their offspring by licking less. When there are fewer dangers
around, the mothers may lick more. New York Times -- 7 October
2003 >>>>
Keith Hudson, Bath, England, <www.evolutionary-economics.org>, <www.handlo.com>, <www.property-portraits.co.uk>
|