A controversial study out of Emory University, reported by Nature, claims that mice can inherit fear from their parents. Mice conditioned to fear the scent of acetophenone, which smells like cherries and almonds apparently, had progeny that had the same reaction to the scent without any conditioning. How does this happen you ask? Well, they don’t know.
The group used electric shocks and acetophenone to condition mice to expect pain whenever the chemical was present. Once the mice were conditioned to associate pain and acetophenone, they had them reproduce and tested their offspring. The researchers found that the conditioned reaction carried on down to this first generation, and even on into a second generation, the equivalent of grandchildren for the original conditioned mice. This response was associated with the methylation of a genetic pathway dubbed Olfr151, known to be associated with the odor receptor for acetophenone. Methylation is kind of a tricky process, whereby methyl groups are added to DNA, typically around a gene’s promoter, thus altering how a gene is expressed without changing the actual nucleotide sequence. These changes, which are heritable but not associated with DNA sequence, are called epigenetic. Anyways.
The group found that this receptor’s genes showed less methylation in the offspring of conditioned mice compared to unconditioned, which would mean they were geared towards expressing more of acetophenone’s receptor. That’s understandable and to be somewhat expected in the conditioned mice, given that increased expression of the receptor would hopefully lend the mice an edge in avoiding a stimulus for pain. What the group can’t explain is how this change managed to work its way into the germ cells and be passed down to offspring. While their data definitely show a sustained response to acetophenone across generations, they can’t explain why an acquired methylation like that would so quickly work its way into the sperm and egg cells. Linnaeus is, no doubt, laughing in his grave at us all. It’s worth noting that the response can be transmitted through either mother or father, including via in vitro fertilization.
The claims the group made in their paper, published in Nature Neuroscience, are being pretty hotly debated. As Nature reports, Timothy Bestor, a molecular biologist at Columbia, thinks methylation is unlikely to have any role in regulating Olfr151, claiming that its promoter lacks the nucleotides necessary for the gene to be methylated. The main problem the group’s results face is that they lack a distinct mechanism for inheritance. Thus far they have been unable to draw a connection between the possible methylation of a parent’s genes and the passage of that epigenetic change on to offspring. Drawing that connection should help to put some of those questions to rest and solidify the epigenetic pathways they claim are at work here. The group thinks there may be an application to humans as well, but that one’s still up in the air, like most of this story really.