Chapter 1: The Transition from Water to Land

When aquatic creatures first ventured onto land, they likely encountered a transformative viral element that took control of their neurons.

During the Devonian period, approximately 360 to 390 million years ago, the first semi-aquatic beings known as tetrapods emerged. These creatures developed limbs with digits instead of fins, enabling them to navigate both shallow waters and terrestrial environments. Notably, tetrapods retained the ability to breathe through both lungs and gills. Over the next 60 to 90 million years, these early tetrapods evolved into amphibians and amniotes, which eventually diversified into reptiles, mammals, and birds, fully occupying terrestrial niches over the course of an additional 100 to 150 million years.

However, amidst this significant transition, a remarkable event occurred: a virus-like element infiltrated their germline cells. This intrusion allowed their neurons to establish synaptic connections essential for learning and memory, marking the dawn of land intelligence. Germline cells, which include reproductive cells such as sperm and eggs, are responsible for passing genetic information to offspring, and thus, the genes derived from these cells are present in every cell of the organism, including neurons.

The ability of neurons to convey genetic information and adjust synaptic connections through mechanisms akin to viruses underlies the brain's capacity for learning, memory, and adaptation.

Section 1.1: The Virus-like Properties of Arc

In the vast landscape of academic research, only a handful of discoveries genuinely stand out. One such landmark study was published in 2018 in the esteemed journal Cell by scientists Pastuzyn et al. from the University of Utah. They investigated the behavior and origins of the activity-regulated cytoskeleton-associated protein, commonly known as Arc.

First identified in the hippocampus of mammals in 1995, Arc is crucial for neuroplasticity and memory formation. In mice, the absence of the Arc gene results in an inability to learn; for instance, mice that find cheese in a specific location fail to remember the route the following day. Memory formation occurs through the establishment and strengthening of synaptic connections between neurons, processes reliant on Arc. Synapses are the points where neurons connect.

Notably, inactivity of Arc has been linked to cognitive disorders and age-related cognitive decline.

Pastuzyn et al. began their investigation by purifying Arc proteins and visualizing them using electron microscopy. To their astonishment, they discovered that Arc forms double-shell structures reminiscent of viral capsids. Initially, scientists and virologists speculated they were observing viruses, but they soon confirmed it was indeed Arc.

Through rigorous purification techniques, such as genetic sequencing and western blotting, they confirmed the proteins' genetic code and molecular structure matched the target, leaving no room for misinterpretation.

During the purification, they also noted that Arc proteins co-purified with RNA, indicating a potential interaction. Subsequent experiments demonstrated that Arc encapsulates messenger RNA (mRNA) within its structure, protecting it from degradation—similar to how viruses transport genes inside their protective capsids.

Within a cell, mRNA conveys genetic instructions from the DNA in the nucleus to the ribosome, where proteins are synthesized. By safely delivering the correct mRNA sequence, one can instruct a cell to produce almost any protein. This is analogous to how COVID-19 mRNA vaccines instruct cells to create spike proteins for immunization.

The first video discusses how animals think and learn, revealing insights into their cognitive processes.

To investigate how neurons utilize Arc, Pastuzyn et al. conducted a series of sophisticated experiments, demonstrating that neurons release extracellular vesicles (EVs) containing Arc. These vesicles carry biological information such as proteins and genes to communicate with other cells. In this case, neurons release Arc in EVs to instruct nearby neurons to create new synaptic connections for memory formation.

The researchers noted, "Here, we show that mammalian Arc protein exhibits many hallmarks of Gag proteins encoded by retroviruses and retrotransposons: self-assembly into capsids, RNA encapsulation, release in EVs, and intercellular transmission of RNA."

This virus-like behavior of Arc in controlling nearby cells is unique to neurons, fundamentally shaping the brain's capability for learning and memory.

Jason Shepherd, PhD, who led the study, humorously acknowledged the implications: "I can see what people are thinking: Is memory a virus?"

Summary of Key Findings:

• Arc is essential for learning and memory as it facilitates synaptic connections.
• Remarkably, Arc behaves like a virus, forming capsids to encapsulate mRNA in extracellular vesicles (EVs), allowing for genetic information transfer between neurons.

The second video delves into the playful aspects of mental health, discussing the animals that inhabit the human brain.

Section 1.2: The Evolutionary Path of Arc

Arc did not exist prior to the emergence of tetrapods, as the gene is absent in fish. This suggests that Arc played a critical role in the genesis of land intelligence.

To unveil its evolutionary origins, scientists utilize phylogenetics to reconstruct the evolutionary lineage of a protein by comparing gene sequences across species. By aligning these sequences, researchers can trace the gene's ancestry back to a common ancestor, revealing how it has evolved over time.

Pastuzyn et al. mapped the evolutionary tree of the Arc protein sequence, demonstrating that Arc from species such as mice, humans, and lizards aligns with that of tetrapods, signifying its high conservation and stability since its inception in tetrapods 360 to 390 million years ago.

The Gag gene from gypsy elements in a fish species closely related to tetrapods serves as Arc's nearest gene relative. Interestingly, fruit flies also possess the Arc protein, which shares evolutionary connections with the Gag gene found in ants and silkworms.

This evolutionary mapping indicates that tetrapod Arc and insect Arc share different ancestors, suggesting that the emergence of Arc occurred independently twice in land-dwelling species.

In summary, the closest evolutionary relative of Arc is the Gag gene from gypsy retrotransposons in fish. This indicates that the Arc gene likely facilitated the dawn of land intelligence.

The Role of Gypsy Retrotransposons

Gypsy retrotransposons are self-replicating genetic elements capable of moving within an organism’s genome. They behave similarly to retroviruses by copying and inserting their genetic material into new locations within DNA, contributing to genetic diversity throughout evolutionary history.

Retrotransposons are not viruses, though they share a close relationship with retroviruses, which include the human immunodeficiency virus (HIV). Both types of elements can insert their genetic material into a host's DNA, but retroviruses can spread between organisms, while retrotransposons are inherited through reproduction.

The genetic structure of retroviruses consists of Gag, Pol, and Env genes, while retrotransposons only contain the Gag and Pol genes. The primary distinction lies in the absence of the Env gene in retrotransposons.

Pastuzyn et al. discovered that Arc contains a sequence corresponding to Gag, reinforcing the notion that retrotransposons can form capsids to encapsulate their genetic material, similar to retroviruses.

Recap:

• Arc's closest relative is the Gag gene from gypsy retrotransposons in fish, signifying its role in the evolution of land intelligence.
• Gypsy retrotransposons, which include Gag and Pol genes, are closely related to retroviruses that encompass Gag, Pol, and Env genes.

Ultimately, the evolution of Arc has profoundly influenced the cognitive capabilities of land animals. The integration of the retrotransposon Gag gene into the genomes of tetrapods enabled them to adapt to the challenges of terrestrial life by developing memory-forming capacities.

Conclusion: The Story of Evolving Intelligence

The remarkable tale of how brain intelligence developed in terrestrial creatures like ourselves is a testament to evolutionary ingenuity. It highlights the intricate interplay of genetic elements that have shaped our cognitive abilities.

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