The "fear" in the "Survival of the Fittest" is caused by Junk DNA

Article “Fear extinction is regulated by the activity of long noncoding RNAs at the synapse” by Zhou et al., Nature (11/23)

Delving Deeper: Fear Extinction and the Role of lncRNAs

Fear extinction is a crucial cognitive process that allows us to overcome negative experiences and build resilience. It involves weakening the association between a stimulus and a fearful response. Until recently, the mechanisms underlying this process remained largely elusive.

A Novel Player Emerges:

A groundbreaking study published in Nature in 2023 by Yujie Zhou and colleagues has shed light on a novel mechanism for fear extinction: the activity of long noncoding RNAs (lncRNAs) at the synapse. These lncRNAs are surprisingly abundant in the prefrontal cortex, a brain region heavily involved in learning and memory.

The Star of the Show: A Gas5 Variant:

Among the identified lncRNAs, one specific variant, a splice variant of Gas5, stood out as crucial for fear extinction memory. This variant interacts with RNA binding proteins, orchestrating the activity-dependent trafficking and clustering of RNA granules within the synapse. These RNA granules are dynamic assemblies of RNA molecules and associated proteins, known to play critical roles in local protein synthesis and synaptic plasticity.

Knockdown Disrupts Extinction:

The researchers used sophisticated techniques to selectively knock down the Gas5 variant in the prefrontal cortex of mice. This manipulation resulted in a significant impairment in fear extinction memory, further demonstrating the vital role of this lncRNA in the process.

Beyond Fear Extinction:

The study by Zhou et al. marks a significant breakthrough in understanding the molecular underpinnings of fear extinction. It reveals a new layer of complexity in this crucial process and provides a novel target for potential therapeutic interventions. Moreover, the findings raise intriguing questions about the broader role of lncRNAs in other forms of learning and memory, paving the way for future investigations.

Future Directions:

Several exciting avenues remain to be explored:

• Mechanism Elucidation: A deeper understanding of the precise mechanisms by which the Gas5 variant regulates RNA granule activity is crucial.

• LncRNA Landscape: Investigating the roles of other lncRNAs in fear extinction and other memory processes is key to uncovering their broader significance.

• Therapeutic Implications: Exploring the potential of manipulating lncRNA activity for developing novel treatments for anxiety disorders and PTSD is a promising direction.

The study by Zhou et al. represents a significant leap forward in our understanding of fear extinction and the fascinating world of lncRNAs. It opens up exciting new avenues for research and sparks hope for the development of novel therapeutic strategies for mental health disorders.

The discovery of long noncoding RNAs (lncRNAs) (aka Junk dna) and their diverse functional roles have raised questions about the traditional neo darwinian view of evolution. While neo darwinism focuses on the role of mutations in protein-coding genes driving evolutionary change, lncRNAs challenge this perspective by demonstrating how non-coding regions of the genome can contribute to phenotypic differences. Here's how lncRNAs specifically challenge neo darwinism:

1. Expanding the Evolutionary Landscape: Traditionally, evolution was thought to primarily occur through the gradual accumulation of mutations in protein-coding genes, leading to changes in protein function and ultimately organismal traits. However, lncRNAs reveal that a significant portion of the genome previously considered "Junk DNA" is actually transcribed and functional. 

2. Functional Diversity and Complexity: LncRNAs are involved in a wide range of biological processes, including gene expression regulation, chromosome organization, and development. This functional diversity suggests that lncRNAs can contribute to a vast array of phenotypic traits, further expanding the scope of evolutionary change possible.

3. Challenging the Central Dogma: The central dogma of molecular biology states that DNA is transcribed into RNA, which is then translated into protein. However, lncRNAs demonstrate that RNA itself can have diverse functional roles without being translated into protein. This challenges the traditional view of information flow and suggests that evolution can operate through non-protein-coding mechanisms.

4. Neutral Evolution and Exaptation: Some argue that the evolution of lncRNAs might not be driven by direct selection but rather by neutral evolution, where non-functional mutations accumulate over time. However, even under neutral evolution, lncRNAs could be "exapted" - co-opted for new functions later in evolutionary history. This suggests that lncRNA evolution may be more complex than previously thought and involves non-selective forces.

5. Rapid Evolution and Phenotypic Plasticity: LncRNAs are often characterized by rapid evolution and high turnover rates. This suggests that lncRNAs can evolve quickly in response to environmental changes, contributing to phenotypic plasticity and adaptation. This challenges the neo darwinian concept of gradual accumulation of mutations, suggesting that evolution can also occur through rapid changes in non-coding regions.

Overall, the discovery and study of lncRNAs challenge neo darwinism by expanding the scope of evolutionary change and demonstrating that non-protein-coding regions play a significant role in shaping organismal phenotypes. While the full extent of their evolutionary impact remains to be explored, lncRNAs offer a new perspective on how evolution operates and contribute to a more comprehensive understanding of the genetic basis of phenotypic variation. It suggests neo darwinism needs revision if not replacement.