All Your Memories Are Stored By One Weird, Ancient Molecule

Memory works in what way? The deeper into this we delve, the more questions appear about how memory appeared in the first place. An important breakthrough was achieved in 1995 when the Arc protein was discovered, demonstrating how it contributes to the consolidation of memory through plastic changes in neurons.

Photo by Andrés Gómez on Unsplash

The Arc picture just got much more interesting, because this protein is already a big deal. A study published in 2017 in the journal Cell argues that Arc evolved in the brain as a result of a chance encounter millions of years ago. The researchers argued that the arc gene developed as a result of a random chance encounter. Like how scientists say that our cells’ mitochondria come from bacteria that our ancient ancestors ingested, the Arc protein came from a virus that our ancient ancestors ingested.

After capturing an image of Arc which looked remarkably like a viral capsid, the enveloping protein coat within which a virus’s genetic material resides for carriage to host cells, the researchers knew they were onto something.

Jason Shepherd, an assistant professor of neurobiology at the University of Utah, a study coauthor, says, “At the time, we knew little about Arc’s function or evolutionary history.” Arc is one of Shepherd’s research interests. To be honest, I almost stopped caring about the protein. Our curiosity was piqued as soon as we saw the capsids.”

Proteins in the brain do not last very long, despite memories lasting nearly a lifetime, which challenges neuroscientists’ understanding of memory. Memory consolidation requires plastic changes in neuron structures, which means that the neuron structure must change as a result.

Arc plays a role in this. The results of previous research on rats showed that Arc disrupted memory consolidation, suggesting Arc is essential to neuroplasticity.

These findings suggest Arc’s viral origin, a finding that scientists never expected to discover.

As a means of verifying this theory, the team tested whether Arc is really acting as a virus. According to research, the Arc capsid contains its own RNA. They found that when the Arc capsids were introduced into a mouse brain cell culture, their RNA was transferred — just as it is with viral infections.

In a statement, the study’s lead author, postdoctoral fellow Elissa Pastuzyn, Ph.D., says, “We knew Arc was unusual in many ways, but we were stunned when we realized it could transport RNA cell-to-cell.” We are unaware of any non-viral proteins acting this way.

A retrotransposon, the ancestor of modern retroviruses, collected its DNA in a four-legged mammal between 350 and 400 million years ago, researchers believe. Several retrotransposons may have been created at the same time. The conclusions of this research complicate our understanding of life’s evolutionary past. The mutations that made us who we are today did not just happen by chance, we actually borrowed biology from other cells and organisms to make us. Our DNA is infused with theirs.

This gene is involved in the generation of synaptic plasticity in mammalian brain, as well as various types of information storage. The molecular function of Arc and its evolutionary origins remain largely unknown. A structure derived from Arc encapsulates RNA by self-assembling into a virus-like capsid. Arc protein, which is endogenous to neurons, is released from extracellular vesicles that allow Arc mRNA to cross into new target cells, where it is translated activity-dependently. The mRNA of Arc can be transferred into the cytoplasm of neurons by endocytosed Arc capsids. In these results, Arc shares many of the molecular properties of its retroviral Gag counterpart. Retrotransposons Ty3/gypsy are also ancestors to retroviruses, and Arc originates from a vertebrate lineage of those retrotransposons. According to our findings, Gag retroelements have been used to mediate intercellular communication within the nervous system during evolution.

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