Sunday, August 24, 2008


Last night I was at a party at the home of SF writer Craig DeLancey, and the question of epigenetics came up. (I have to tell you, parties among writers/scientists are the only venues this sort of thing comes up for me. It doesn't happen, for instance, at meetings of the Home Owners' Association.) I was familiar with the basic idea of epigenetics, which is that having genes isn't the whole story; the greater part is how, when, how often, and in what order those genes are switched on or off during the development of an organism. Some of the mechanisms by which this is done (such as methylation) are becoming well understood. The overall reasons, as yet, are mostly not.

The cool part, however, is that the changes inside the cell caused by epigenetics can be inheritable, in at least three ways. Two of them I was aware of before last night's party; the other one I was not.

First, as everybody knows, stem cells have the complete genome encased in each cell. Stem cells develop into various kinds of cells by switching on, say, the brain-developing genes and switching off the toe-developing genes. As these newly differentiated cells divide, the switching-on-or-off carries into the two resulting daughter cells, ensuring that you don't get a toe inside your brain. This is Epigenesis I.

In Epigenesis II, adult cells that divide also bequeath their switched-on-or-off pattern to daughter cells. Thus, not only do insulin-processing cells beget more insulin-processing cells, if yours are doing a lousy job of this task, so will your new ones. This epigenesis is thought to be the result of the transference of existing cell structures in the two dividing cells, as well as of any genes that may be malfunctioning. No real surprise here.

The surprise comes in Epigenesis III. Some traits acquired in mothers as a result of how their patterns of cells react to environmental toxins seems to be inherited by their offspring. This sounds almost LaMarckian, but there is proof from experiments with agouti mice. Mice with identical genomes (they were clones) were exposed to high concentrations of BPA (that's the same toxin being yelled about with regard to plastic water bottles). The offspring of those so exposed were a different color (yellow rather than brown) and gained weight easily. This might have been construed as damage to their genomes -- except that the new offspring were then not exposed to any more BPA, and still their offspring showed heritable patterns of color and weight gain, presumably as a result of the passing on of Gen II's epigenetic patterns. And the abnormalities were reversed by feeding the mice diets high in soy, indicating they were not set-in-stone genetic instructions.

This boggles my mind. Not only does it shift everything I thought I knew about genes, it also lends terrible weight to that most Biblical of curses: The sins of the fathers shall be passed onto the children, unto the fourth generation.

Other than disturbing my mind -- or maybe because of it -- it was a terrific party.


Mary Robinette Kowal said...

Lamarkian was one of the first thoughts that went through my head as well. Boggling comes in at a close second. Thanks for posting about this.

TheOFloinn said...

ensuring that you don't get a toe inside your brain.

Perhaps it is this very lack that drives so many to put their foot in their mouth.

That being said -- and I had to say it -- I am struck by the Aristotelian nature of it. The Aristotelians and Thomists said that a thing's nature would express itself in a manner congenial with its environment. (They were suspicious of experiment because the artifice of experiment might interfere with the natural environment and so the resulting behavior would not reflect the thing's nature.

Another example of the epigenetic effect is from an old WSJ science column: two populations of cloned water fleas, one raised in a tank containing a chemical marker for a predatory fish, the other in a tank free of such markers. The first developed the crunchy "helmet" characteristic of that species of flea; the other did not. Yet, the genomes of the two populations were identical. It was the environmental cue that made the difference.

So, the origin of "species." Mutation may not be necessary in many cases; only a radically changed environment. There was a story recently about a Mediterranean lizard which, shifted from one island to another, not only switched diets (and stopped eating its own young) but developed a new internal organ. Shazaam. No wonder new species appear so suddenly in the fossil record, hein?

qiihoskeh said...

I had just been thinking about something related when I saw this.

Given that most of the extragenetic chemicals come from the mother, shouldn't it be "the sins of the mothers"? Hmmm.

The test subject, "Eve", was exposed to [certain chemicals] present in fruit such as ... the effects on both the immediate offspring ... and descendants ...
This experiment was paid for by a grant from ....

(first comment here)

Nancy Kress said...

Yes, epigenetic effects were coming only from the mother --- that we know of so far! So it should be "sins of the mother," but I didn't want to take too many liberties with the quote.

Kosmo said...

This reminds me of research in Huntington's disease where it has been shown the age-of-onset of the disease is influenced by which parent you inherit the gene from.

T. Kosmatka.

(By strange coincidence, I was posting on my blog today about genetics, and somebody suggested I check out your post.)

cd said...

Also: what if a social condition changed epigenetic conditions? For example, imagine if stress hormones had a relevant and inheritable effect. Then certain social patterns might be very strongly inherited, even though they were in fact potentially revisable with social alteration alone. That is, "it's human nature" might appear true of some behaviors because the social conditions have tremendous epigenetic intertia....d

autumnmist said...

I just found your blog - the Beggars trilogy was one of my very favorites as a teenager.

I'm currently a graduate student in human genetics so I thought I'd add something here.

It's definitely sins of the mother and/or father and/or grandparents. One very well-studied example of epigenetic inheritance and imprinting* is Prader-Willi Syndrome/Angelman Syndrome (see relevant Wikipedia/MedlinePlus articles). These syndromes occur when genes in a certain segment of chromosome 15 are deleted in a given individual, with a caveat: when the paternally-inherited (from the the father) copies of the genes are deleted/missing, the individual has Prader-Willi Syndrome and when the maternally-inherited copies of the genes are deleted, the individual has Angelman Syndrome.

*imprinting is the phenomena where the parent of origin for a given gene affects the activity of the gene through some sort of biochemical modification of the gene's/DNA overall structure but not actual sequence