Intercalation-mediated synthesis and replication: A new approach to the origin of life

We propose that a molecular midwife, a flat molecule approximately 10 Angst rom x 10 Angstrom with two hydrophobic faces, was essential to the origin o f life. This molecule was positively charged, water soluble and did not str ongly associate with itself in solution. It may have been a derivative of p hthalocyanine that no longer exists on the Earth today, and might have been formed solely from hydrogen cyanide and formaldehyde. The midwife tended t o intercalate between side groups (bases, similar to those in RNA) of polym ers to form stacks, which incorporated bare bases. The midwife alternated i n these stacks with hydrogen-bonded tetrads of bases. Under conditions of l ow water activity, as in a desert during the day, bare bases in the stacks were joined together by neutral and chemically heterogeneous backbones of n o fixed chirality. The components of the backbones were the products of the formose reaction of formaldehyde, and were involved in the reversible form ation of N-glycosides and acetals catalysed by divalent metal ions. The fin al product of this assemblage was a fully intercalated quadruplex of four i nformation-containing polymer strands (four proto-RNA molecules). This proc ess constituted replication of the original polymer that had seeded the for mation of the stack. The stack structure ensured that the polymer's base se quence was replicated faithfully despite the lack of both homochirality and chemical homogeneity in the backbone. At night, water from condensing dew would suddenly come in contact with these products, quenching all chemical reactions and releasing midwife molecules and single- or double-stranded pr oto-RNA. Evaporation of water during the day then gave new stacks containin g one or two proto-RNA strands, bare bases, and midwife molecules, which co uld begin a new replication cycle. Our model also allows for the generation of new stacks and the extension of existing ones, without restricting the base sequence of either, thereby providing a source of genetic information. The proto-RNA replication cycle is driven purely by concentration changes caused by the Sun and the rotation of the Earth. We propose that this syste m as a whole could have gradually evolved into the RNA World. (C) 2000 Acad emic Press.