Is Epigenetic Inheritance Actually “Genetic”?
A new study published late last month in Genome Biology entitled, “Contribution of genetic variation to transgenerational inheritance of DNA methylation” reported on what has been a controversial topic for a number of years now. Specifically, the paper addressed the theory that epigenetic changes can be acquired in an organism’s lifetime and be passed down to the offspring without change to the genome itself. There has been great interest in the field of epigenetics in the last few decades and the idea of transgenerational epigenetic inheritance has been an exciting one to many people, even though the exact mechanism of modified inheritance is still unknown.
Back in September of last year, I covered this topic, proposing that generational changes to the epigenome may actually be reflective of minor mutations to the noncoding sequences of DNA. I’m sure I’m not the first person to have proposed such an idea, though it was certainly new to me.
Case in point, McRae et al. (2014) have provided enticing evidence that the similarities in epigenetic patterning amongst individual families are closely tied to variations in the genetic code between families. Also, about 20% of epigenetic differences over generations within the same family appear to be caused be DNA sequence variation.
This doesn’t completely discount the idea that epimutation could occur and be inherited from parent to offspring with absolutely no change in the genetic sequence itself–, after all, what’s with the other 80%? But it does start to look more likely that what we once interpreted as “epimutation” is actually “mutation” all along.
If that’s the case, why is the epigenome still so friggin’ awesome?
I’ll tell you why. Even though it’s possible that the seat of inheritance lies mainly within the DNA sequence itself, the epigenome is a prime regulator of genome stability. –And not only a regulator of general genome stability, but it could feasibly target mutations to specific genes. For instance, the epigenome (in its broadest sense, including histones, methyl groups, transcription factors, silencers, metal ions, etc.) determines the expression or suppression of a given gene. It is also known that transcriptional activation of a gene increases the mutation rate in that gene. Therefore, changes to the epigenome could increase the likelihood that a target gene might mutate and that mutation could be passed to succeeding generations. Ergo, epimutation can drive mutation. So, even though we’re not talking about giraffes’ necks, Lamarck still may not have been that far off.
I don’t find this study particularly shocking, nor do I consider it a heavy blow to those who have been battling to convince the scientific community of the importance of the epigenome in development and illness– although I’m sure there’s those traditional geneticists who will try to use it as proof of the Almighty Genome. No, to me this simply clarifies mysteries and reconfirms for me the division of labor in the nucleus of the cell. The genome might be the brawn behind many aspects of inheritance, but the epigenome is the brains. And it’s probably one of the biggest drivers of evolution, even if it has to use that pesky genome as an intermediary step to do so.