Researchers have discovered an ancient protein fold, called the double-zeta β-barrel (DZBB), that may have been a crucial stepping stone in the early evolution of life on Earth. This missing link sheds light on how complex biomolecular machines like genomes and protein synthesis could have arisen from simpler precursors. The findings challenge the limits of current AI models and provide insights into the Cambrian explosion of life.
Unraveling an Evolutionary Mystery
In a historic first, a team of researchers from the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have managed to unveil a never-before-seen protein fold which could have been instrumental in the inception of life on Earth. Called the DZBB, for short, this ancient complex provides a missing bridge in perhaps the most important question science has ever faced: how could features of Biomolecular machines that control gene expression and build new proteins evolve over simpler precursors?
By employing a mix of lab experiments and computational simulations, the researchers reconstructed the evolutionary trajectory of this primordial protein fold. They began with a fold common to both DNA and RNA polymerases (the enzymes that copy the genome or make copies of individual genes) and demonstrated that this same fold could have evolved into folds seen in today’s ribosomal proteins—key components of the cellular machinery that makes proteins—with just a few simple, feasible mutations.
A Flexible Platform for Molecular Evolution
The structure of DZBB is akin to a tightly wound version of a protein origami, which can scaffold into other important shapes with only small rearrangements. And is what can make DZBB such an exciting possible evolutionary intermediary.
It is possible that DZBB represents an initial stage of a subsequent evolutionary process to generate the extreme diversity of molecular machines observed in life today, somewhat analogous to the Cambrian explosion of animal phyla. This malleable nature — which might allow it to take on multiple stable forms in different conditions — could have helped the first proteins adapt and evolve rapidly and give rise to the complex biomolecular systems we recognize today.
Tech Stack: The shortcomings of existing AI models
The discovery of DZBB also underscores that current artificial intelligence (AI) models are not equipped to recognize such intricate protein entities. Despite even the most recent machine-learning algorithms, this ancient fold could not have been predicted using computational methods alone.
“Since the responses from AI are strongly influenced by the training dataset and experimental validation is inevitably required for purely unexpected discoveries,” Shunsuke Tagami, another author on the study, tells ZDNet. Through the use of AI and machine learning, we can further our understanding of the beginnings and evolution of life on Earth even if those studies are laboratory-based.
The new results suggest that DZBB may have been processing these raw ingredients of life from the time it first formed. Why did this ancient fold disappear from modern proteins, despite being so important to driving the emergence of molecular machines that control gene expression? It is possible, says Tagami, that DZBB was a fleeting protein form that emerged briefly during a key evolutionary juncture before other more specialised structures took its place.
