Science is rarely straightforward. Many times, scientists embark on a study looking for evidence for a particular hypothesis, and in the process, they come across something totally unexpected and different from their original purpose. It doesn’t happen often, but when it does, it can be so exciting.
For Matthew Eroglu, it started with worms behaving oddly in his lab at the University of Toronto. He was studying cancer signaling pathways in these nematodes but wound up stumbling upon a new way that traits can be passed down through generations — one that doesn’t rely on DNA or RNA.
Over generations, the worms he studied became less fertile and more feminine. Eventually, some stopped producing sperm altogether. “We started with a different focus,” Eroglu recalls.
What they found is a new form of epigenetic inheritance driven by amyloid proteins — structures more commonly linked to diseases like Alzheimer’s. This discovery may help explain mysteries like “missing heritability” — the fact that many traits and diseases run in families without clear genetic explanations.
A New Layer of Inheritance
Under the microscope, the researchers spotted something unusual: tiny, glowing green structures in the worms’ reproductive cells. Eroglu describes them as “glowing blobs.” These structures, which the team named herasomes, turned out to be aggregates of amyloid proteins—the same type of proteins whose accumulation in the brain is thought to be responsible for neurodegenerative diseases like Alzheimer’s.
Amyloids are proteins that fold into sticky, clump-prone structures. In the worms, these clumps accumulated when two specific genes, mstr-1 and mstr-2, were mutated. The clumps disrupt sex determination in the worms, leading to more feminized offspring. Remarkably, these protein clumps were passed down through generations, although the worms’ DNA remained unaltered.
Scientists have known for decades that genes alone don’t account for the full picture of inheritance. For instance, we now know about epigenetics — changes in gene expression that don’t involve alterations in DNA code — where mechanisms like small RNA molecules and chemical modifications to chromatin can alter traits that can be passed down to subsequent generations.
However, this is the first time that proteins have been identified as carriers of inheritance.
Inheritance In Protein
“Matthew really opened up a new form of epigenetic inheritance,” says Dr. Brent Derry, Eroglu’s supervisor. “He found that amyloids can be inherited, marking a significant discovery in protein-based epigenetic inheritance. This changes the way we think about this field entirely.”
Could these findings partially explain the “missing inheritability” conundrum? Many common diseases run in families. In some families, the risk of developing a particular disease can approach 50%. Genome-wide association studies (GWAS) have successfully identified some of the genes that contribute to this risk, but for some diseases, a substantial portion remains unexplained. This gap has been called the ‘hidden heritability’ or ‘missing heritability.’
“There are a lot of traits and disorders that we know are passed on from parents to offspring if we look at family trees and so on,” Eroglu said. “But when people have done genome-wide association studies trying to link these traits to mutations or variants in genes, they frequently fall short of explaining all of the heritability that we see.”
An Unlikely Discovery
Amyloid-based inheritance could be part of the answer. These proteins, whose clumps replicate and spread like prions, offer a mechanism for passing traits from one generation to the next without altering DNA. “Amyloid aggregates have been observed in human oocytes,” Eroglu told El Pais, though their function remains unclear.
The worms studied by the researchers, C. elegans, are hermaphrodites that typically produce both sperm and eggs. But when the researchers deactivated certain genes related to cancer signaling, the worms began producing fewer sperm and more eggs with each generation. Under stressful conditions, like slightly higher temperatures, the effect was even more pronounced.
With each generation, the worms produced fewer sperm and more female oocytes. Ultimately, they only produced oocytes. The team spent years unraveling the mystery. They ruled out known epigenetic mechanisms and eventually zeroed in on the glowing herasomes. Injecting amyloids from feminized worms into normal worms triggered the same changes, proving that the proteins alone could drive the effect.
Could This Happen in Humans?
For now, the discovery remains confined to worms. But if amyloid-based inheritance is confirmed in mammals, it could provide an entirely new explanation for how diseases like type 2 diabetes, some cancers, and neurological disorders are passed down. “At least one group is investigating whether this amyloid inheritance occurs in rats,” Eroglu said.
DNA remains the primary blueprint for life. But this research suggests that there may be another, overlooked layer to how traits move across generations.
As Eroglu puts it, “Who knows what you could do? Could we discover something that, in fact, doesn’t change sex but changes some other traits? Or predict diseases that we couldn’t base on DNA alone?”
The findings appeared in the journal Nature Cell Biology.
