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A model for life's start


One of the greatest mysteries, and one that continues to fascinate scientists worldwide, concerns how life emerged on primeval earth. The accepted notion is that before the appearance of living organisms there was a stage of chemical evolution that involved selection within inanimate chemical mixtures. This stage is thought to have led eventually to the crucial moment when self-replicating molecules arose. As self-replication is a fundamental characteristic of living entities, such an event is often defined as the birth of life.

The self-replication of molecular systems is often viewed in the context of information content. Many scientists believe that life began with the spontaneous emergence of biopolymers, such as proteins or RNA, which store information in a sequence of chemical units. Experiments simulating the conditions on earth billions of years ago have shown how such chemical units -- some of the building blocks of proteins and RNA -- could appear spontaneously. Yet the emergence of proteins or self-replicating RNA molecules remained a mystery.

This puzzle started Prof. Doron Lancet of the Crown Human Genome Center in the Weizmann Institute and his students Daniel Segre and Dafna Ben-Eli on a journey in search of alternatives to proteins and RNA. They developed a model, suggesting a new route for the origin of life that is based on lipid molecules. This model is described in an article published in Proceedings of the National Academy of Sciences (PNAS).

Lipids are oily substances, and the chief ingredients of cell membranes. Readily synthesized under simulated prebiological conditions, they have two different aspects -- hydrophilic (water-attracting) and hydrophobic (water-repelling). Because of their dual nature, they have the tendency to spontaneously form supramolecular structures made up of thousands of molecular units. An example is lipid assemblies (micelles), which have even been shown capable of growing and splitting in a fashion reminiscent of cell replication. Yet a critical question was left unanswered: how could lipid assemblies propagate and carry information?

The model proposed by Lancet and his colleagues offers a solution. They surmise that, early on, lipid-like compounds existed in a great diversity of shapes and forms. They show mathematically that under such conditions lipid assemblies could contain almost as much information as an RNA strand or a protein chain. Information would be stored in the assembly's composition -- in the exact amount of each of its compounds, rather than in a sequence of molecular "beads" on a string. A useful analogy would be the way in which perfume is discerned by receptors in the nose. The information depends on each ingredient's proportion in the mixture, but the order in which aromas are added is unimportant.

Thus, the authors argue, heterogeneous lipid assemblies may be thought of as having a "compositional genome." Their computer simulations also show that a droplet-like lipid assembly, when growing and splitting, could be passed on to future generations with reasonable constancy. A crucial aspect of the model is how such molecular inheritance is made possible. In present-day cells, protein enzyme catalysts facilitate the replication of information-containing DNA. In the early, prebiological era, the same lipid-like substances carrying the information might have performed catalysis. Molecules already present inside a droplet would function as a molecular selection committee, enhancing the rate of entry for some and rejecting others.

Lancet, Segre, and Ben-Eli designed a simulation that shows, solely on the basis of physiochemical principles, how lipid droplets accrete, grow, split, self-replicate, accumulate compositional mutations, and become involved in a complex evolutionary game. Significantly, it is entire assemblies, with their complex mixtures of relatively small molecules that are replicated. This differs from older models, in which it is a single, long RNA polymer that is copied. The scientists' model makes very few chemical assumptions and involves a rich molecular behavior reminiscent of life processes. It therefore has the potential of constituting the long-sought bridge leading from the inanimate world to that of living organisms.
This research has already attracted considerable interest and was quoted in the recently published new edition of the classic Origins of Life by Freeman Dyson of the Princeton Institute for Advanced Study. The next important question to be answered: How could lipid droplets undergo the numerous transitions needed to lead to living cells as we now know them? The study marks the first footfall in a long journey to come.
Lipids droplets accrete, grow and split