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Ann N Y Acad Sci. 1999 May 18;870:119-32.

RNA processing in evolution. The logic of soft-wired genomes.

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Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.


Direct read-out of information from DNA into RNA allows the genome to be faithfully reproduced in RNA. This outcome occurs in what may be called "hard-wired" organisms. On the other hand, in what we refer to as "soft-wired" organisms, RNA is processed extensively, allowing a number of different messages to be produced from the same gene. As a consequence, the nucleotide sequences present in RNA (referred to here as the ribotype) differ from those present in DNA (the genotype). In soft-wired organisms, RNA processing can be thought of as a series of steps, one or more of which have two mutually exclusive outcomes: a "default" outcome and an "alternative" outcome. In the presence of appropriate regulatory signals, the RNA is processed using the alternative pathway, while the default pathway is used in their absence. The setup is functionally equivalent to that found in binary "logic gates." In both cases, "logical operations" are implemented by using regulatory signals to establish a conditional relationship between input and output and can be described using the Boolean operators AND, OR, and NOT. In the case of RNA processing events, the outcomes can be used either to directly regulate cellular responses or to control other RNA processing events. In the latter case, "networks" are established that make processing of one RNA contingent on another. Such networks allow cells to respond to their surroundings by changing the connectivity between different RNA processing events, using RNA as a substrate to compute an appropriate response. As such logical operations impact phenotype, they are subject to natural selection. Through reverse transcription, successful outcomes can be incorporated into the genome.

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