How peptide amyloids could have paved the way for life on Earth

Life on Earth originated around 3.7 billion years ago. Despite this being a crucial milestone in our planet’s history, the precise molecular mechanisms behind its emergence remain largely unknown.

Scientists have proposed many theories to explain the origin of life. Two stand out: the primordial soup theory and the RNA world hypothesis.

Both these theories follow a linear way of thinking by trying to zero in on a single molecule or class of molecules that led to life on Earth.

However, one of the main challenges with this linear thinking is the uncertainty about which specific molecule or class of molecules emerged first because the elaborate chemical networks supporting life are not likely to have originated from a few exceedingly complex molecules.

So now scientists are looking at a different scenario. A study published in the Journal of the American Chemical Society has now proposed this co-evolutionary model where many molecules (like peptides and nucleic acids) evolved together.

Rather than a single molecule being the origin of life, as traditionally thought, the interdependence among various classes of molecules is crucial to the emergence of life.

Let’s explore this alternative approach and examine how this new perspective helps to address the complexity of prebiotic chemistry and the challenges of identifying a singular starting point for life.

Theories on the origin of life

Prebiotic chemistry is the branch of biochemistry that studies chemical reactions and processes that occurred before life on Earth.

There are currently two primary theories surrounding the origin of life. First, let’s examine the Primordial Soup theory.

Primordial Soup Theory

In the 1950s, Stanley Miller and Harold Urey introduced this theory, suggesting that life on Earth originated in a “primordial soup,” a mixture of organic molecules.

Imagine early Earth having an atmosphere rich in gases like ammonia and methane. These gases were subject to lightning, which led to the formation of complex organic molecules, like amino acids (these are the fundamental building blocks of life).

These complex organic molecules collected in the Earth’s oceans over time and became the primordial soup that eventually fostered life.

RNA World Hypothesis

On the other hand, the RNA World Hypothesis suggests that RNA spontaneously emerged on Earth as a precursor to life. According to this theory, RNA molecules were critical in the early phases of life development because they stored genetic information and catalyzed chemical reactions.

Think of RNA, or ribonucleic acid, as DNA’s cousin. While DNA has two strands and is considered the blueprint for life, RNA transmits genetic information and only has one strand.

The Primordial Soup Theory is supported by experiments such as the Miller-Urey experiment, which demonstrated the ability to generate organic molecules under recreated early Earth conditions. Despite the experimental evidence, the theory cannot specify which molecules or components in the soup caused life to develop.

Similarly, the RNA World Hypothesis is supported by the discovery of ribozymes, which are RNA molecules that function as RNA and also catalyze reactions! RNA’s versatility is also suggested to support its role in the origin of life.

Yet, it can’t explain the spontaneous formation of RNA molecules on early Earth and if they could orchestrate the complexity of life’s beginnings alone.

The proposed alternative 

Given the limitations of the two theories, the researchers in this study introduce the notion that peptide amyloids, with their repetitive structure, played a pivotal role in the emergence of life.

Peptide amyloids, which are sometimes referred to as just amyloids, are aggregates of short chains of amino acids known as peptides. These peptides arrange themselves in a specific way to create pleated sheet-like structures, which interact with each other to create a stable and ordered fibrous structure.

Amyloids are deemed prebiotically relevant due to their unique properties, which might have influenced early life stages. Here are four main reasons researchers focused on them:

1. Some amyloids can exhibit self-replicating behavior. It parallels a fundamental property of living organisms–the ability to reproduce or create copies of themselves.
2. Some amyloids exhibit catalytic capabilities, accelerating chemical reactions like complex biochemical processes.
3. Amyloids have a stable and ordered structure, providing a scaffold for interactions with other molecules. This structural stability could have contributed to the organization of early molecular systems.
4. Amyloids can interact with nucleotides (building blocks of DNA and RNA). This interaction could have influenced the formation and stability of genetic material in the prebiotic environment.

RNA-amyloid interactions

While challenging traditional theories, the researchers delve into the intricate dynamics of RNA-amyloid interactions to unravel a compelling narrative of co-evolution.

Interaction between genetic material and amyloids

The researchers synthesized various peptide amyloids but were all created focusing on replicative potential and structural stability. They exposed the short RNA sequences to amyloid, wanting to understand the binding patterns between the two and how this affected RNA stability.

Researchers observed a unique sequence-dependent binding mechanism between the two, suggesting that the binding is influenced by the sequence of nucleotides in the RNA molecules.

The mutually beneficial connection stabilizes the structure of amyloids, demonstrating their periodic and well-defined nature while simultaneously acting as a guardian by curbing the hydrolysis of RNAs (which is the breaking down of RNA).

The study noted that binding small RNAs and peptide amyloids involves at least three ribonucleotides.

The binding itself depended on general electrostatic interactions (which are interactions between charged particles) and other interactions based on the RNA sequence. In other words, the interactions are a mix of overall affinity and specific connections through certain parts of the RNA molecules.

Amyloids as catalysts

Moreover, the researchers challenge traditional views on the origin of the genetic code. They suggest that the genetic code’s specificity emerged before larger RNA molecules capable of binding to amino acids.

The periodic and well-defined surface of amyloids was also identified as having the potential to increase the local concentration and order of nucleotides. This means that they can act as catalysts in biological reactions involving nucleotides.

The researchers suggest that the sequence-selective interaction, coupled with the catalytic ability of amyloids, could have played a role in the synthesis of distinct and longer ribonucleotides, which is a significant step in the evolution of catalytic RNAs.

Conclusion

The traditional linear narratives of the primordial soup and the RNA world hypothesis find a thought-provoking companion in a co-evolutionary theory.

The researchers’ discovery that amyloids can bind to DNA and RNA and affect their stability opens a new chapter in our understanding of the origin of life.

Crucially, the research questions our understanding of evolutionary dynamics. It suggests cooperation instead of competition as the force driving evolution on early Earth.

The stabilizing interaction between amyloids and genetic material, enhancing the stability of both hints at a cooperative venture that might have been instrumental in life’s emergence. “After all, there was likely no shortage of space or resources back then,” said Prof. Roland Riek, lead author of the study, in a press release.  

In the ancient primordial soup, where molecules drifted in sparse and disorderly surroundings, collaboration among molecules may have been vital, and amyloids were crucial to the emergence of life.