1 THE LIPID WORLD: FROM CATALYTIC AND INFORMATIONAL HEADGROUPS TO MICELLE REPLICATION AND EVOLUTION WITHOUT NUCLEIC ACIDS ARREN BAR-EVEN, BARAK SHENHAV, RAN KAFRI AND DORON LANCET Department of Molecular Genetics and the Crown Human Genome Center, the Weizmann Institute of Science, Rehovot 76100, Israel 1. Lipid World And The GARD Model A widespread notion is that life arose from a single molecular replicator, probably a self-copying polynucleotide, in an RNA World (Joyce, 2002). We have proposed an alternative Lipid World scenario as an early evolutionary step in the emergence of cellular life on Earth (Segre et al., 2001). This concept combines the potential chemical activities of lipids and other amphiphiles, with their capacity to undergo spontaneous self-organization into supramolecular structures, such as micelles and bilayers. In quantitative, chemically-realistic computer simulations of our Graded Autocatalysis Replication Domain (GARD) model (Segre et al., 1998), we have shown that prebiotic molecular networks, potentially existing within assemblies of lipid-like molecules, manifest a behavior similar to self reproduction or self-replication. Because amphiphile assemblies may form readily and spontaneously under prebiotic conditions (Deamer, 1985), the Lipid World scenario may represent an intermediate “mesobiotic” phase, bridging an a-biotic random collection of organic molecules with a biotic protocell that contains long biopolymers, as well as more intricate information storage, catalysis and replication (Shenhav et al., 2003). In our model, lipid-like amphiphiles may possess a very large variety of chemical structures, including head- groups that resemble amino-acids or nucleotides. Catalysis is proposed to be exerted by such diverse chemical moieties, enhancing amphiphile exchange rates as well the formation of more complex head-groups with similarity to peptides or oligonucleotides. In a more recent version of our model (Polymer GARD or P-GARD), a path is delineated for the gradually increased dependence on linear molecular sequences (Shenhav et al., in press). A most central notion in our P-GARD model is that life began with monomers only, and later proceeded to evolve biopolymers. This is in strict contrast to the widespread view, epitomized by the RNA World concept, whereby the abiotic formation of biopolymers is a prerequisite for life. In other words, RNA World or protein World proponents assert that a molecular entities devoid of biopolymers cannot possess the basic attributes of life. This credo derives from the premise that a living entity has to contain information and transmit it to progeny via replication, and that such a sequence