"The Unseen Genome: Beyond DNA"

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.

But biologists are starting to decipher a separate and much more malleable layer of information encoded within the chromosomes."

p. 106

Genome metaphor | Methylation anomaly | Glossary | expression : suppression | Findings

"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:

the book of inheritance,

the source code of cells,

the blueprint for a life.

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."

"A genome operates like a machine with several complex interacting parts. The epigenetic parts should be easier to modify with medicine than the DNA sequence has been"

"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"

p. 108

The big buttocks anomaly in sheep: is called Callipyge genes, are involved with RNAs and suppression of traits.

p. 109

"Such overdominance' effects seem to be rare. Imprinting however, is quite common, especially in flowering plants."

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.

p. 110

Genome metaphor | Methylation anomaly | Glossary | expression : suppression | Findings

"How imprinting works is still not entirely understood. But DNA methylation seems to play a very significant role."

p. 110

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."

p. 111

"But revolting as it may seem, our DNA is filled with genetic parasites." says Timothy H. Bestor of Columbia Un.

"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."

Genome metaphor | Methylation anomaly | Related ideas | expression : suppression | Findings

"The Unseen Genome: Beyond DNA"

Glossary of Terms:

Human Genome Project

DNA , deoxyribonucleic acid, is a polypeptide or long molecule,

an inheritable molecule having four distinct nitrogen bases: A=T; C=G.

DNA mapping -- the predictive model of where traits occur on alleles.

DNA sequences -- the order of nitrogenous base pairs on a chromosome.

RNA -- believed to be the predecessor of DNA a different base U, replaces C.
RNA only genes -- small sections of protein coding interspersed in DNA.

Alleles -- the DNA strand, usually paired to make up the full chromosome.

Transposons -- or -- jumping genes, movable sections of gene sequences.

methyl, CH3, or an organic molecule comprised of three hydrogen atoms and attached to a carbon atom with a valence of negative one (Will accept a bond).

methylation -- or suppression of expressions

Imprinting -- one allele is more active than the other half in genes

Genome metaphor | Methylation anomaly | beginning | expression : suppression | Findings

"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..."

p. 111

"Volume Control for Genes" graphic of five stages in expression & suppression

chemical changes to chromosome
chromosomes are made of chromatin
an intricate histone code -- governs gene expression
genes can also be suppressed by methyl tags
Transposons -- called jumping genes can clone themselves

p. 112

Genome metaphor | Methylation anomaly | beginning | expression : suppression | Glossary

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."

"The new view of the genomic machine is emerging....Those 30,000-odd protein coding genes, so important yet so immutable, are not the only instruction set to which cells refer. Noncoding DNA matters. The shape of the chromatin matters. And all of these are subject to manipulation."

"'There is a whole new universe out there that we have been blind to,' Bestor says...."

p. 113

see further: Richard Lewontin, The Triple Helix