Can one parent silence the other’s genes? Natural ‘paramutations’ found in mice

Amazing stuff!

"... The new research ... indicates genes from one parent can sometimes unexpectedly silence those inherited from the other, and that the effect could persist for generations. If the findings extend to humans, they could help explain why some people who carry a disease-causing genetic variant never develop the condition.

The phenomenon, named paramutation, challenges the conventional view of inheritance and had not been shown to naturally occur in mammals. It’s a form of epigenetics, in which chemical modifications to DNA sequences or proteins they wrap around turn genes on or off. In paramutation, through a process scientists don’t fully understand, one copy of a gene can silence the dominant version inherited from the other parent by coating it with methyl groups.

Paramutation’s discovery in mice marks a major shift in how scientists think about epigenetic inheritance in mammals ..."

"... Since its discovery in maize in 1950s, paramutation has been observed in other plants, fruit flies, and nematodes. The effects can be visible.  ...

Until recently, researchers lacked the tools to reliably trace which parent has passed along a particular version of a gene, called an allele. Traditional DNA sequencing didn’t read long sequences of DNA to see the variation needed to distinguish maternal and paternal alleles—the short stretches were often identical, obscuring their origin. But the arrival of long-read sequencing changed that, as researchers could examine enough DNA from a gene at once to link individual alleles to a specific parent. ..."

"... “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,” ..."

From the abstract:

"Epigenetic mechanisms such as genomic imprinting demonstrate that molecular inheritance can deviate from typical Mendelian patterns. Despite this, the intergenerational inheritance of DNA methylation remains poorly understood.

Here we developed a genome-wide approach to study epigenetic inheritance in mice using long-read nanopore sequencing. Using this approach in both liver and muscle, we found that ~93% of autosomal epigenetic inheritance patterns followed Mendel’s laws, primarily driven by cis-acting methylation quantitative trait loci.

However, we also identified extensive non-Mendelian inheritance, including emergent epigenetic inheritance patterns, widespread sex-specific DNA methylation patterns localized to the liver, and five seemingly new autosomal and X-linked imprinted genes.

Notably, we also report an example of naturally occurring intergenerational paramutation, confirmed over strain-specific transposable elements within Capn11 and highly likely at Vps37c.

Overall, an unexpectedly high ~7% of autosomal epigenetic inheritance patterns identified were non-Mendelian, highlighting the importance of epigenetic information in the analysis of inherited traits and disorders."

Can one parent silence the other’s genes? Natural ‘paramutations’ found in mice | Science | AAAS "Odd phenomenon first seen in plants could explain puzzling disease inheritance patterns"

Lab Study Reveals Patterns of Inheritance That Defy Mendel's Laws (original news release)

Non-Mendelian inheritance of DNA methylation patterns in mice (open access)

Fig. 1: Identification and characterization of Mendelian and non-Mendelian epigenetic inheritance patterns.