Journal of Biological Physics 20: 201-210, 1994. 201 © 1995 KluwerAcademic Publishers. Printed in the Netherlands. EVOLUTION OF THE CELLULAR COMMUNICATION SYSTEM: An Analysis in the Computational Paradigm K. TAHIR SHAH International Centre for Theoretical Physics, P.O. Box 586, 34100 Trieste, Italy Abstract. We discuss the problem of the evolution of the cellular communication system from the RNA world to progenote to the modern cell. Our method analyses syntactical structure of molecular fossils in the non-coding regions of DNA within the information- processing gene model developed earlier. We concluded that sequence-specific binding is an ancient communication process with its origin in the RNA world. Moreover, we illustrate, our viewpoint using four evolution snapshots from the first RNA segments, some 4.1 billion years ago, to the first cell, 3.8 billion years ago. 1. Introduction Modern cells are extremely complicated systems. There are some 750 different types of small molecules, 2000 distinct macromolecular species and between 1000 to 4000 different enzymes. Such a complex machinery had most likely a modest beginning some 3.8 billion years ago when the first cell, our Universal Ancestor or Progenote, appeared. The origin of our progenote's information encoding and communication system goes back to another 400 million years in the RNA world, according to our analysis. Early cellular evolution differed in both tempo and mode, to use Simpson's description [1]. It differed, moreover, in the overall complexity of the cellular system of the contemporary processes. But there are unanswered questions. For example, what is the relationship between the first cell and the first segments of nucleotides which appeared around 4.2 billion years ago? Or, how did these only-RNA sequences evolve into an RNA-DNA-Protein cell with its intra- and inter- cellular communication systems? These are hard questions per se. These become harder because there is no likelihood of ever finding any fossil of the RNA world. We are forced to make a rational guess as to what happened between 4.2 and 3.8 billion years - the era of the RNA world. Moreover, any theoretical construct should be compatible with what we know about the contemporary cell. Such an extrapolation, of course, is a pre-condition which any model should satisfy. Almost three decades ago, Pauling and Zuckerkandel [2] suggested a way out of this difficulty and proposed to use molecules as documents of evolutionary history. Later, Woese and his collaborators [3, 4, 5, 6] developed a method to infer evolutionary history from DNA sequences based on comparative analysis. A mathematical theory of inferring evolutionary history from DNA sequence is developed by Kannan and Warnow [7]. They proved that the Character Compatibility Problem