Epigenetics: An introduction, some recent research, and a dash of history.

I'm going to write a little about #epigenetics (warning: speculation abounds), because I've received a number of requests centred around it recently. The field is very popular right now; I understand the appeal, as it's currently one of the more interesting areas of genetics. Recently, demonstrations amongst mammals (here's one example:http://goo.gl/BEcw7) have been disruptive to the field, proving some elements of "Lamarckism" right. That's a bold claim; Richard Dawkins stated epigenetic effects "are mildly interesting, but they cast no doubt whatsoever on the theory of the selfish gene". This is true; Lamarck (18th century biologist) was still incorrect, in that "soft evolution" is not the main mechanism for evolution. Currently, it looks like all long-term evolution is due to natural selection, selfish replicating units of information, with some short-term (few generation) heritable adaptations influenced by experience.

Substances that alter body chemistry could feasibly cause epigenetic change. Alcohol, nicotine, any number of carcinogens, mind-altering substances, could all cause the body to undergo stress (biological stress, a departure from homoeostasis) which has been shown to cause epigenetic effects in mice. Psychologically, research has also shown that traditionally non-physical troubles such as mental illness (depression, anxiety, mood disorders), can have chemical effects on the brain similar to those caused by psychoactive drugs, which is a possible pathway by which they could cause epigenetic change. There is a huge confounding factor when researchers try to study these effects, however: children mostly grow up in the homes of those who gave them their genes. If they didn't, the parents who gave them their genes are generally hard to contact, making research opportunities scarce. Why does this matter? It becomes extremely difficult to differentiate between changes which are epigenetic, caused by parents or close ancestors behaviour during production of gametes, and psychological, caused by parental influence upon children as they are raised.

For certain disorders that we know are mostly genetic, like autism, it becomes easier to quantify. A lot of headlines have run stating that research has linked the age of mothers with their child's likelihood of getting autism; it is unclear how this process could occur from epigenetic effects, as women do not constantly produce their gametes (it is highly unlikely for such a change to occur due to actual nucleotide sequence damage when copying, as the copying of genetic information is very high-fidelity, error rates of 10^-6 to 10^-8 [http://www.jbc.org/content/279/17/16895.full]). A possible answer is in the fine print of the research report it is based on (Gillberg, Christopher, "Maternal age and

infantile autism" J. of Autism and Developmental Disorders, 1980, p293-297): age of the father wasn't mentioned until into the actual report, more than an overeager journalist was willing to read. The age of the father was also significantly above average, and it is now feasible that epigenetic effects from the fathers' lifestyle or age, made possible by the constantly renewed male gametes, could have caused the strong correlations seen.

None of this leads, of course, to biological determinism. Just as our forebears have possibly predisposed us, so we can make choices which will avoid negative influences upon ourselves and our genetic descendants (if we have them), and in the future, research may allow us to make lifestyle choices which will actively improve their chances (although that, even more so than the rest of what I've talked about, is highly speculative).

That speculation is rampant, of course, as there are still a lot of unknowns in the field of epigenetics; no-one's currently sure of a theoretical maximum for the number of generations something like a histone change or DNA methylation could stick around for, for example. A lot of uncertainty is to be expected in such a young science, but it also leads to a lot of excitement. Ninety years ago, a young geneticist might have been ridiculed by his fellows for suggesting Lamarck-ist claims which we now know to be true; Paul Kammerer suffered exactly that fate, and ended up committing suicide. New Scientist ran an article a couple of years ago, by Laura Spinney, entitled "Born scared: How your parents' trauma marks your genes"; it shows quite poignantly how much the field has changed, and articles like it understandably draw ire from some experienced geneticists or evolutionary biologists (like Richard Dawkins) who see much of the recent hubbub to be at best overstatement of what is most certainly not a revolution, and at worst yellow journalism. Maybe the solution is some drier titles until we've got some certainty? #genetics #biology #science #dnaday

Figure 1 (Public Domain Mark 1)