For more than a century, biology students have learned the neat rules of inheritance laid down by Gregor Mendel and his pea plants: alleles sort themselves, dominant traits prevail, recessive ones fade. Yet research published in the journal Nature Genetics last month indicates that the genetic story is far more complicated than most textbooks detail.
Researchers led by Andrew Feinberg of Johns Hopkins University and David Threadgill of Texas A&M tracked how mice inherit chemical modifications to DNA known as epigenetic marks. These marks do not alter the DNA sequence itself, but rather can regulate how genes function, turning genes off and on, and, what is more, they can be passed down through generations.
The team identified about 7% of these epigenetic patterns that violated Mendel’s laws of inheritance. Some were examples of classical genomic imprinting, in which an allele is silenced depending on its parent of origin (sperm or egg). However, the anomalies themselves were far weirder.
“Non‑Mendelian patterns of inheriting epigenetics could be a faster way to acquire diverse or new traits than alterations in the genomic sequence itself, especially in response to environmental pressures,” says Feinberg.
One of them was paramutation, a phenomenon documented in both plants and flies but apparently never observed in mammals. In one instance, methylation on a gene called Capn11, important for sperm development, seemed to spread from one allele to the other like some chemical contagion.
“It’s almost like the methylation is transferred to another allele,” Feinberg explains.
More remarkably, there were novel methylation changes that arose in the offspring but were absent in both parents. Methylation appeared to arise spontaneously, adds Feinberg.
These insights came from a detailed analysis of three generations of mice, using long-read DNA sequencing to simultaneously read both the genetic code and methylation marks across the genome. In total, they found 522 examples of non-Mendelian inheritance, including 54 cases of spontaneous emergence of new epigenetic traits.
“This work may convince scientists to integrate both genomics and epigenomics more often for a complete understanding of how traits that produce disease and healthy states are inherited,” says Kasper Hansen of Johns Hopkins.
The implications are far broader than just in mice. Feinberg and coworkers plan to use their approach on human genomic data, with the hope of discovering how environmental factors such as diet, stress, or trauma can structure inheritance in ways never imagined by Mendel.
For genetics, the message is clear: the code is only part of the story. These chemical marks, layered on top of the genome, may very well be rewriting the rules of heredity in real time.
