A tRNA world

Published: May 22, 2012, 11 a.m.

Knowledge about the kinetics of chemical reactions in cells is important for an understanding\nof signaling pathways and regulation. Even though there are many kinetic measurements\nof in vitro reactions in literature, methods for in vivo measurements are sparse. With help\nof Temperature Oscillation Optical Lock-in (TOOL) microscopy we measure the kinetics of\nDNA hybridization inside cells and detect signicant acceleration or deceleration compared to\nin vitro measurements, dependent on the DNA sample. The dierences can not be explained\nby molecular crowding eects. Only models that take the background interactions with genomic\nDNA and RNA as well as the activity of single stranded and double stranded binding\nproteins into account, can be tted to data. The results imply that the biological relevance\nof kinetic rates measured in vitro has to be rejudged carefully.\nThe RNA world hypothesis predicts catalytic molecules based on RNA, as for example\nearly replicators, as precursor of modern biology. But how can a pool of appropriate RNA\nmolecules arise under early earth conditions? In a Gillespie-model, we observe the length distribution,\nsecondary structure and sequences of a pool of RNA molecules in porous rocks like\nthey appear near sites of volcanic activity. We assume a monomer in\nux, a length dependent\nout\nux, a random, non-templated polymerisation and a degradation that is much stronger\nfor single stranded than for double stranded RNA. After equilibrium is reached, the pool\nis populated with many hairpin-like structures due to the selection pressure for hybridized\nstrands that can be bricks for RNA machines.\nOnce sequence motifs and their complements appear in the reactor, they protect each other\nand are present longer than statistically expected. This "protection by hybridization" has\nthe same ngerprint as a weak replication. As a consequence, the pool does not cover the\nfull sequence space but includes more similar sequences, which is an important condition for\nchemical reactions.\nReplication of genetic information by RNA molecules is considered to be a key process in the\nbeginning of evolution. It is so crucial that traces of this early replication are expected to be\npresent in key processes of modern biology. We present a replication scheme based on hairpins\nderived from the sequence of tRNA that replicates the genetic information about a succession\nof sequence snippets. The replication is driven by temperature oscillations as they occur\nnaturally inside of porous rocks in presence of temperature gradients, and independent on\nexternal chemical energy sources. It is selective for correct information and shows exponential\ngrowth rates with doubling times in the range of seconds to minutes and is thereby the fastest\nearly replicator in the literature.\nThe replication scheme can naturally be expanded to longer successions by using double\nhairpins derived from full tRNA sequences by only few mutations. By charging double hairpins\nwith amino acids or peptides, the proposed replication bridges the gap from the RNA world\nto modern biology by oering a rudimentary translation mechanism, that sorts amino acids\nto chains according to genetic information.