Non-genomic evolution.

Michael New and Andrew Pohorille

The ability of organic matter to self-organize into self-sustaining, reproducing and evolving structures governed the transformation of matter from inanimate to animate on the early earth. Probably the earliest such structures were protocells -- membrane-enclosed, cell-like structures capable of supporting essential life functions. Recent advances in molecular biology, chemistry and computer modeling have created possibilities for constructing laboratory models of protocells and exploring their properties. One such effort has been undertaken recently by experimentalists and theorists from NASA-Ames Research Center, Harvard Medical School and the University of California.

The main hypothesis underlying the NASA-Harvard-UC project is that initially protocells evolved in the absence of a genome. Only later did coded information storage (e.g., the nucleic acid-based systems employed by modern cells) emerge. Central to this new concept of non-genomic evolution is the emergence of peptide-bond forming protoenzymes. They were initially very weak, non-specific catalysts, generating peptides of various lengths and sequences. A few of the peptides so generated could have been better catalysts of peptide bond formation than the protoenzymes which formed them. These better protoenzymes would, in turn, generate even more peptides, increasing the rate at which a protocell ``searched'' the space of all peptides for functional ones. Some of the peptides created in this search would undoubtedly function as proteases. Since proteases cleave unstructured peptides more rapidly than structured ones, and since functional peptides have to have an ordered structure, the proteases would preferentially destroy non-functional peptides. Occasionally, the newly produced peptides would be capable of performing novel functions eventually leading to the emergence of nucleic acids and their coupling with peptides.

The goal of the proposed work is to examine the evolutionary potential of a non-genomic system, i.e. to establish what conditions are required for non-genomic evolution to take place and to determine whether these conditions are biochemically plausible. We will employ a simple, computationally tractable model which is still capable of capturing the essential biochemical features of the real system. In this model, we will consider several ubiquitous metabolic reactions in a protocell, such as the formation and hydrolysis of peptide bonds, transduction of environmental energy to chemical energy stored in high energy compounds, activation of amino acids and synthesis of membrane-forming material that leads to growth and division of protocells. All these processes occur through catalyzed, albeit possibly very inefficient, pathways. All peptides are characterized by three traits: their length, their catalytic efficiencies and the degree of structure. Since microscopic rules that relate the peptide sequence to its catalytic efficiency are not known, we will adopt a stochastic model, in which this relationship is captured by assuming that the efficiencies of peptides of length n for catalyzing reactions of type A are distributed with probabilities . In the simplest implementation, these probability distributions are Gaussian. The position of the maximum of this Gaussian depends, in a sigmoidal fashion, on the length of the polymer. This means that initially the efficiencies increase, on average, only slightly with the length of the polymer. Only when peptides reach lengths sufficient for them to be able to adopt an ordered three-dimensional structure do the average efficiencies start increasing markedly. Then, for even longer polymers, the average efficiencies again stabilize, since gaining additional structure no longer produces significant improvement in catalytic properties.

Preliminary results on a simple system containing only synthesis and hydrolysis of peptides has demonstrated that non-genomic evolution is possible under a relatively wide range of conditions. In fact, we either observed systems that clearly evolve or systems that do not evolve at all. This suggests a possibility of phase transition between evolving and non-evolving systems.

Demonstrating non-genomic evolution both theoretically and experimentally (in the accompanying project, discussed above) would shed fundamental, new light at the origin and evolution of the protocellular metabolism.

References:

``An Inherited Efficiencies Model of Non-genomic Evolution'', M. H. New and A. Pohorille, Simulation Theory and Practice, 8, 199-208, 2000.

``Models of Protocellular Structures, Functions and Evolution'', A. Pohorille and M. H. New, Proceedings of Rencontres de Blois `Frontiers of Life', 15 June-1 July 2000, Chateau de Blois, France. Submitted.