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.
Science Over a Cuppa 
Long time no post but that’s just POL, pace of life. This is fun – I’ve always been a closet Lamarkian so it’s really great to see others express this feeling, too. In fact it gives me the courage to say it to the World “Yes, I am a Lamarkian”.
Wow, that felt liberating – now everybody knows and I’ve finally come out in my true colours.
Thanks Emily for giving me the opportunity to do that, you’ve made my day!
Happy to help, greencentre! 😉
The theory of punctuated equilibrium states that evolutionary processes go through long periods of relative stability punctuated by bursts of rapid evolutionary change.
http://www.stephenjaygould.org/library/gould_structure.html
‘That is certainly true in many cases, because the chances of each of those critical changing forms having been preserved as fossils are small. But in 1972, evolutionary scientists Stephen Jay Gould and Niles Eldredge proposed another explanation, which they called “punctuated equilibrium.” That is, species are generally stable, changing little for millions of years. This leisurely pace is “punctuated” by a rapid burst of change that results in a new species and that leaves few fossils behind’.
Exposures to new environmental risk factors that generate sperm or egg mutations, the increased rate of de novo gene mutations in humans since the industrial revolution is accelerating. Are we now entering a period of rapid evolutionary change? Molina examined the types of sperm mutations in healthy male volunteers:
http://www.ncbi.nlm.nih.gov/pubmed/20931230
Not all mutations are necessarily deleterious; in fact, many new mutations spurred on by environmental risk factors may prove to be beneficial.
That poses an interesting question, Robert, as to whether we’re on a mutational upswing or not. As this point it would be difficult to say one way or another without being able to see the end result (i.e., some substantially new adaptation), but certainly something to wonder about.
Slightly off topic on this thread, but wondering what your take is on maladaptive/ Cell Danger Response view of autism, ala Robert Naviaux? You are probably familiar with his MIA suramin studies, and here is his most recent video presentation http://vimeo.com/99038257 , and the theory paper here http://www.sciencedirect.com/science/article/pii/S1567724913002390
I think the CDR could definitely play a role in some cases, although how large this subgroup might be is another story. But with my genetics work, it’s obvious that there is a subgroup of risk genes that are involved in multiple aspects of that CDR, including mitochondrial-related genes, as well as genes involved in purine metabolism. So, yeah, definitely a probable subgroup which may predispose towards autism. But there’s still probably a lot of heterogeneity too, in that it’s not the root of “all autism”. It’s probably one of a number of roots, all of which target similar cellular processes during development, resulting in an overlapping phenotype.
Actually probably not off topic either, as the possible prenatal (or germline?) insults that reprogram this CDR would have epigentic and possibly also directly mutagenic effects …
That’s entirely possibly too. Just as an example, the favorite Valproic Acid definitely targets the epigenome partly through HDAC inhibition, but may also promote gene instability through a similar action. The latter needs further confirmation, however, but definitely a potential example of exactly what you’re talking about.
… reading up on purinergic signalling in development, it looks like it plays a big role in differentiation of neuronal progenitor cells ” We report here that purines drive the expansion of ventricular zone neural stem and progenitor cells, and that purine receptor activation is required for progenitor cells to be maintained as such. Neural progenitors expressed P2Y purinergic receptors and mobilized intracellular calcium in response to agonist. Receptor antagonists suppressed proliferation and permitted differentiation into neurons and glia in vitro, while subsequent removal of purinergic inhibition restored progenitor cell expansion…”
ops, hit sent too soon … “These data suggest that purine nucleotides act as proliferation signals for neural progenitor cells, and thereby serve as negative regulators of terminal neuronal differentiation. As a result, progenitor cell-derived neurogenesis is thus associated with regions of both active purinergic signaling and modulation thereof.” http://www.sciencedirect.com/science/article/pii/S0012160606012188
Yep, that’s right in line with what I’m finding. So I would imagine CDR would affect neurogenesis as well.