Israeli study probes if lipids came first in the origin of life

A prevailing scientific scenario for the chemical origin of life focuses on RNA (ribonucleic acid) and proteins, biopolymers that without which there would be no life today. But a new study suggests that it's not plausible that these complex molecules could spontaneously appear prebiotically.

Instead, the authors of the study have proposed that life originated in lipids, chemical compounds similar to soaps or detergents, which can interact with both water and fats. Such simple lipid molecules, which compose the membranes of living cells today, are more likely to spontaneously emerge prebiotically and generate molecular assemblies. These multi-molecule assemblies can undergo fission, grow, and self copy--prerequisites for evolution.

The researchers present their new work on this "lipid first" scenario in the Royal Society of Chemistry journal, Chemical Society Review, Sept. 20.

Authors Amit Kahana, Svetlana Maslov, and Doron Lancet, from the Department of Molecular Genetics at the Weizmann Institute of Science in Israel, discuss qualities that make lipid assemblies a more likely candidate for life's beginning.

In particular, the researchers focus on the stereospecificity recognition ability of lipids. This property allows some lipid clusters to interact in lifelike ways with specific small and large molecules, which is a necessary precursor for evolution to take place. They argue that the lipid-first scenario is on par with the RNA-first view in many characteristics and, in some characteristics, "reveals superiority" to the RNA-first view.

Dynamic lipid aptamers

The particular structures the researchers studied are dynamic aptamers, lipid analogs of short pieces of single-stranded RNA or DNA material. "Aptamers are stably threaded oligonucleotide or peptide molecules found to recognize a molecular target," said senior author Doron Lancet. These capacities are found to occur when libraries of aptamers are screened, so as to find the ones that specifically recognize target chemical compounds.

The researchers focus on dynamic lipid aptamers, which Lancet defined as "patches on the surface of a non-covalent lipid assembly that dynamically self-organize to form target recognition sites." Non-covalent means that the lipids in the assembly are weakly associated, allowing movement and exchange.

Lancet said that "evidence for such molecular recognition is presented in cited research papers on protein binding with precision to small lipid domains of cellular membrane, and in chemical studies on target recognition discovered via micellar library screens."

Micelles are the name for nanoscale conglomerates of lipid molecules that appear to be the best candidates for seeding life, Lancet said.

Reviewing the scientific work supporting the existence of lipid aptamers, the researchers describe the evidence showing how they might play a role in the origin of life, such as catalysis of certain chemical reactions, without the presence of enzymes, leading to the formation of catalytic networks.

The authors have previously shown that these, in turn, lead to lipid assembly reproduction with information transfer across generations, Lancet said.

"Our origin-of-life model invokes recognition between target molecules and amphiphilic lipid on the surface of micellar lipid assemblies," he said. (Amphiphiles are chemical compounds, like soaps or detergents, which can combine with both water and fats.)

The RNA and protein model

Regarding why he thought the RNA-protein model for origin-of-life research was inadequate, Lancet gave three reasons:

"First, the emergence and survival of both RNA and proteins in a messy prebiotic environment is highly unlikely," he said. 

"Second, RNA cannot assume the function of protein encoder before the advent of the terribly complex ribosomes, a prebiotic near-impossibility. Third, the full capacity of RNA to self-reproduce has never been demonstrated experimentally."

The lipid-first theory hasn't been pursued, according to Lancet, because "much of origin-of-life research is based on the viewpoint that life began with molecular functionalities comparable to those of present-day cells. No lipid catalysts exist in present-day life, hence proto-cellular lipids are described solely as partition formers, copying their singular contemporary role."

Lancet made the case that the lipid-first theory can "perform chores" which many believe that only RNA and protein can perform. "Our alternative origin scenario focuses on the possibility that before the advent of protein and RNA enzymes, lipid assemblies assumed catalytic roles, which paved the way to autocatalytic micelles with compositional reproduction capacities, leading to selection and evolution."

The future

The researchers acknowledge that further research is necessary to provide more experimental evidence for their viewpoint.

"We hope that our research direction will reach the point of paradigm shift, as further experiments are done using advanced technologies that can track at single-molecule-resolution billions of lipid micelles," Lancet said. "Groundbreaking progress can in parallel come from advanced molecular dynamics simulations, that can follow the fate of growing and splitting lipid assemblies and show their capacity to undergo Darwinian evolution."

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A. Kahana et al. Dynamic lipid aptamers: non-polymeric chemical path to early life.

Chem. Soc. Rev., Sept. 20, 2021. DOI: 10.1039/D1CS00633A