June 8, 2000 REHOVOT, ISRAEL (June 5, 2000) -- One of the greatest mysteries, which continuously fascinates many scientists worldwide, concerns the way by which life emerged on primeval Earth. The accepted notion is that prior to the appearance of living organisms, there was a stage of chemical evolution, which involved selection within inanimate chemical mixtures. This is thought to have eventually led to the crucial moment, when self-replicating molecules arose. As self-replication is a most fundamental characteristic of living entities, such an event is often defined as the birth of life.
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, where information is stored in the sequence of chemical units. Experiments mimicking the conditions on Earth billions of years ago have shown how such chemical units, e.g. some of the building blocks of proteins and RNA, could appear spontaneously. Yet, the emergence of proteins or self-replicating RNA molecules remained enigmatic.
This started Prof. Doron Lancet of the Crown Human Genome Center in the Weizmann Institute of Science, and his students, Daniel Segre and Dafna Ben-Eli, on a journey leading to alternatives to proteins and RNA. They have developed a model, suggesting a new route for the origin of life, based on lipid molecules. This model is described in an article published in a recent issue of the Proceedings of the National Academy of Science, USA.
Lipids are oily substances, known as chief ingredients of the cell's membranes. Lipids have two different aspects − one hydrophilic (water-attracting), and the other hydrophobic (water-repelling). They get readily synthesized under simulated prebiological conditions, and because of their bipartite nature, have the tendency to spontaneously form supramolecular structures made of thousands of molecular units. This is exemplified in lipid assemblies (micelles), which have even been shown to be capable of growing and splitting in a fashion reminiscent of cell replication. Yet a critical question was left unanswered: how could lipid assemblies carry and propagate information?
The model proposed by Lancet and colleagues offers a solution. They surmise that early on, lipid-like compounds existed in a very large 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, i.e. 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 that of perfume: the information – the scent as discerned by receptors in the nose – 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". They further demonstrate how a droplet-like lipid assembly, when growing and splitting, could manifest a form of inheritance. Their computer simulations show how a compositional genome would be handed down with some fidelity to the offspring assemblies. A crucial aspect of the model is how such molecular inheritance is made possible. In present-day cells, the replication of information-containing DNA is facilitated by protein enzyme catalysts. In the early prebiological era, catalysis could be performed by the same lipid-like substances that carry the information. 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 computerized simulation that shows how, based solely on physiochemical principles, lipid droplets with idiosyncratic compositions accrete, grow, split, self-replicate, accumulate compositional mutations, and get involved in a complex evolutionary game. Importantly, it is entire assemblies, with their complex mixtures of relatively small molecules that are replicated.
This differs from the older models, in which a single, long RNA polymer is what gets copied. The scientists' model makes very few chemical assumptions and derives 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 book Origins of Life by Freeman Dyson from the Princeton Institute of 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? In this sense, the study marks the first footfall in a long journey to come.
Professor Lancet holds the Ralph and Lois Silver Professorial Chair in Neurogenomics. Professor Lancet's research is supported by The Ebner Family Biomedical Research Foundation, Israel; The Henri and Francoise Glasberg Foundation, France; The Alfried Krupp von Bohlen und Halbach Stiftung, Germany; La Foundation Raphael et Regina Levy, France; Dr. Ernst Nathan Fund for Biomedical Research, USA; The Kalman and Ida Wolens Foundation, Corsicana, Texas and The Wolfson Family Charitable Trust, England.
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