|Genetic dogma dies|
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Unseen Genome: Beyond DNA"
W. Wayt Gibbs
Scientific American (December, 2003) pp.106-113.
genetic vs. epigenetic consideration in the functioning, expression and suppression of inherited traits.
Transfer of resistance or susceptibility to environmentally engendered disease conditions due to the transmission of important traits through the chromosomes but outside the DNA.
Chromatin is about 1/3 DNA and 2/3 histones (proteins) that tightly wind or loosely configure the DNA strands of the double helix.
"DNA was once considered the sole repository of heritable information.
"When the final draft of the sequence --the
DNA sequence, scientists can now guess which bits are the genes that are
transcribed into RNA messages and then translated into functional proteins--
was released in April, many said that the string of three billion A, T,
G, and C bases in the human DNA represents:
But in truth, all these metaphors mislead."
"Rather the a genome is a biochemical machine of awesome complexity. Like all machines it operates in three dimensional space, and it has distinct and dynamic interacting parts."
"...in search of explanations for anomalies that contradict the central dogma:"
"In recent years, geneticists....have found that these second and third layers of information distinct from protein-coding genes, connect in surprisingly deep and potent ways to inheritance, development and disease."
"Geneticists have yet to decipher the complex code by which epigenetic marks interact with other components of the genome. But in working outcome of the critical mechanisms, researchers have noticed that the epigenetic part of the genome seems to play crucial roles in growth, aging and cancer."
"Whereas cells doggedly protect their DNA against mutation, they routinely add or erase epigenetic marks"
List of imprinted human genes is now at 75
"In the first few days after conception, nearly all imprinting is removed from the chromosomes. How this happens is a mystery."
but by the time of mid-gestation the imprinting is re-established completely.
"How imprinting works is still not entirely understood. But DNA methylation seems to play a very significant role."
Methyl has an affinity for C or Cytosine bases in the DNA sequence
"Special purpose enzymes take methyl molecules derived from such basic nutrients such as folic acid and vitamin B12, and stick them on to certain C-bases throughout the genome."
"Roughly 45 percent of the human DNA sequence consists of viral genes (or gene fragments) that have copied themselves into the genome during the course of evolution. ...Nearly all this selfish DNA is heavily methylated and rendered inactive."
"In general the more methylated a stretch of DNA, the less likely it is to be transcribed into RNA (and hence proteins) and to carry out its function."
"The Unseen Genome: Beyond DNA"
DNA , deoxyribonucleic acid, is a polypeptide or long molecule,
"The Unseen Genome: Beyond DNA"
"But what happens if the methyl defense falters?"
Experiments raise ...the possibility: Could epigenetic abnormalities accelerate- perhaps even initiate--the genetic chaos that leads to cancer?"
"The idea that a lack of methyl on the DNA can lead to human cancer, is still just a hypothesis..."
"Volume Control for Genes" graphic of five stages in expression & suppression
Lessons: A newer view
"Currently epigenetic reprogramming goes awry in clones
that are made by replacing the DNA in a fertilized egg with DNA from
an adult cell."