[Paleopsych] Epigenetics (We are software, not hardware :-))

[Steve Hovland]

The conventional wisdom on genes goes something like this: DNA is
transcribed onto RNA, which form proteins, which are responsible for just
about every process in the body, from eye color to ability to fight off
illness. But even as the finishing touches were being applied to the
sequencing of the human genome (completed in April 2003), unaccountable
anomalies kept creeping in, strangely reminiscent of the quarks and dark
matter and sundry weird forces that keep muddying the waters of theoretical
physics.

Enter the science of epigenetics, which attempts to explain the mysterious
inner layers of the genetic onion that may account for why identical twins
aren’t exactly identical and other conundrums, including why some people are
predisposed to mental illness while others are not. Scientific American
devotes a two-part article to the topic in its November and December 2003
issues. To summarize:

Only two percent of our DNA - via RNA - codes for proteins. Until very
recently, the rest was considered "junk," the byproduct of millions of years
of evolution. Now scientists are discovering that some of this junk DNA
switches on RNA that may do the work of proteins and interact with other
genetic material. "Malfunctions in RNA-only genes," explains Scientific
American, "can inflict serious damage."

Epigenetics delves deeper into the onion, involving "information stored in
the proteins and chemicals that surround and stick to DNA." Methylation is a
chemical process that, among other things, aids in the transcription of DNA
to RNA and is believed to defend the genome against parasitic genetic
elements called transpons. An 2003 MIT study created mice with an inborn
deficiency of a methylating enzyme. Eighty percent of these mice died of
cancer within nine months. A five-year Human Epigenome Project to map all
the DNA methyl sites was launched in October 2003 in the UK.

A MedLine search of epigenetics and bipolar disorder revealed but two
articles, such is the topic’s novelty. Arturas Petronis MD, PhD, Head of the
Krembil Family Epigenetics Laboratory at the University of Toronto, in an
article in the Nov 2003 American Journal of Medical Genetics, fills in some
of the blanks: We know that there is a high concordance of identical twins
with bipolar disorder, but epigenetics, he explains, may account for the 30
to 70 percent of cases where only one twin has the illness. Identical twins
share the same DNA, but their epigenetic material may be different.
Moreover, whereas DNA variations are permanent, epigenetic changes are in a
process of flux and generally accumulate over time. This may explain, Dr
Petronis theorizes, why bipolar disorder tends to manifest at ages 20–30 and
45-50, which coincides with major hormonal changes, which may "substantially
affect regulation of genes ... via their epigenetic modifications."

The dynamics of epigenetic changes may also account for the fluctuating
course of bipolar, Dr Petronis speculates, perhaps more so than static DNA
variations. Finally, the fact that epigenetic anomalies can be reversed
makes them inviting targets for a new generation of meds, Scientific
American points out.

In a 2003 pilot study, Dr Petronis and his colleagues investigated the
epigenetic gene modification in a section of the dopamine 2 receptor genes
in two pairs of identical twins, one pair with both partners having
schizophrenia and the other having only one partner with the illness. What
they discovered was that the partner with schizophrenia from the mixed pair
had more in common, epigenetically, with the other set of twins than his own
unaffected twin.

This may be the first time you have heard of epigenetics. Clearly, it won’t
be the last.