Scientists Unveil Novel Inheritance Pathway Bypassing DNA

Scientific discovery seldom follows a simple path. Often, researchers initiate an investigation seeking support for a specific theory only to stumble upon entirely unforeseen findings unrelated to their initial objective. Although this occurrence is not frequent, when it happens, it can be incredibly thrilling.

For Matthew Eroglu, everything began when he noticed unusual behavior in worms during an experiment at the University of Toronto. His initial focus was on understanding cancer signaling pathways within these nematode specimens. However, this led him to discover a novel mechanism for transmitting traits across generations, which operates independently from both DNA and RNA mechanisms.

Across generations, the worms under his observation grew progressively less fertile and increasingly feminized. Ultimately, certain specimens ceased producing sperm entirely. "Our initial research had a distinct focus," Eroglu remembers.

What was uncovered is a novel type of epigenetic inheritance fueled by amyloid proteins—structures typically associated with conditions such as Alzheimer's disease. This finding could shed light on enigmas akin to "missing heritability"—the phenomenon where numerous characteristics and illnesses persist within families but lack evident genetic causes.

A Fresh Stratum of Heritage

Through the microscope, the scientists noticed an anomaly: small, luminescent green formations within the worms' reproductive cells. Eroglu refers to them as "gleaming masses." The team dubbed these structures herasomes It turned out these were clusters of amyloid proteins—same as those believed to accumulate in the brain and cause neurodegenerative conditions such as Alzheimer’s disease.

Amyloids are proteins that adopt a configuration which makes them both adhesive and prone to clustering. In the case of the worms, such aggregations occurred whenever two particular genes were active. mstr-1 and mstr-2 The mutations formed clumps that interfered with sex determination in the worms, resulting in more female progeny. Interestingly, these protein aggregates were inherited across generations even though the worms' genetic material stayed unchanged.

For many years, scientists have understood that genes do not entirely explain heredity. We currently recognize the role of epigenetics—modifications in how genes are expressed without changing the underlying DNA sequence. These changes can result from factors such as tiny RNA particles and chemical adjustments to chromatin, which may influence characteristics inherited by future generations.

This is the first instance where proteins have been recognized as carriers of heredity.

Inheritance In Protein

Matthew has truly introduced a novel aspect of epigenetic inheritance," explains Dr. Brent Derry, who supervises Eroglu. "His research reveals that amyloids have the potential for heritability, which marks a crucial breakthrough in understanding protein-driven epigenetic inheritance. This shifts our perspective fundamentally within this scientific domain.

Can these discoveries help elucidate the "missing inheritability" puzzle? It’s widely observed that numerous prevalent illnesses tend to occur within families. For certain conditions, familial risks may be as high as nearly 50%. While genome-wide association studies (GWAS) have pinpointed several genetic factors contributing to this susceptibility, a significant fraction still cannot be accounted for in some cases. This unresolved discrepancy is referred to as 'hidden heritability' or 'missing heritability.'

There are numerous characteristics and conditions that we understand can be inherited from parents to their children when examining family histories," Eroglu stated. "However, when researchers conduct genome-wide association studies aiming to connect these traits with genetic mutations or variations, they often fail to account for all of the observed heritability.

An Unlikely Discovery

Amyloid-based inheritance might provide some answers. These proteins form clusters that replicate and propagate similar to prions, offering a means to transmit characteristics across generations without changing the DNA sequence. "Amyloid aggregates have been seen in human egg cells," Eroglu explained. El Pais , although their purpose is still not well understood.

The worms examined by the scientists, C. elegans They are usually capable of generating both sperm and eggs. However, after deactivating specific genes associated with cancer signaling, the scientists observed that these organisms started producing less sperm and increased amounts of eggs over successive generations. This trend became even more significant under stressful conditions, such as elevated temperatures.

In every new generation, the worms generated less sperm but an increased number of female egg cells. Eventually, they solely produced eggs. This phenomenon puzzled researchers for several years as they worked to uncover the underlying cause. After eliminating conventional epigenetic factors, their investigation led them directly to the luminescent organelles called herasomes. When amyloids extracted from feminized worms were introduced into typical specimens, similar transformations occurred, demonstrating conclusively that these protein structures alone had the power to induce this change.

Can This Occur in Humans?

Currently, these findings are limited to worms. However, should amyloid-driven inheritance be validated in mammals, it might offer a completely fresh perspective on the transmission of conditions such as type 2 diabetes, certain types of cancer, and neurodegenerative illnesses. "A team is exploring whether this form of amyloid inheritance takes place in rats," noted Eroglu.

DNA continues to serve as the main template for life. However, this study indicates that there might be an additional, previously unnoticed mechanism through which characteristics are transmitted between generations.

As Eroglu suggests, "Who knows what possibilities lie ahead? Might we uncover something that alters certain attributes without changing one’s gender? Or perhaps forecast illnesses not solely based on genetic code?"

The results were published in the journal Nature Cell Biology .

The tale initially surfaced on ZME Science . Looking to become smarter each day? Subscribe to our newsletter and keep up-to-date with the newest scientific discoveries.