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<p>The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses. If cytosine concentrations are to be maintained on a worldwide basis, then synthesis must be sufficient to replace depletion. The syntheses described thus far do not possess the necessary speed and selectivity to meet this requirement. The use of drying lagoons as a site for prebiotic synthesis has been suggested as a remedy: synthetic rates would be enhanced by greatly increasing the concentration of the reagents. The lagoon suggestion appears geologically implausible, however. All schemes in which cytosine is synthesized locally and distributed globally also are handicapped in that the enormous dilution that takes place when cytosine is released into a global sea offsets any gain in synthetic efficiency. </p> <p>The possibility remains that a set of unique circumstances produced a batch of cytosine on one or a few occasions on early Earth. The cyanoacetylene-cyanate path seems the most likely candidate yet described for such an event, although problems remain concerning the availability of the reactants. Unless the cytosine produced were quickly processed, however, such an event would not be significant for the origin of life. Decomposition processes would gradually consume the product. </p> <p>This fate would be avoided if the cytosine were used soon after it was made. The rate of cytosine deamination is not affected appreciably when it is part of a nucleotide or single-stranded nucleic acid, but it is slowed by a factor of 140 on incorporation into double-stranded DNA (<a href="http://www.biology-online.org/articles/references-prebiotic_cytosine_synthesis_a_critical_analysis_and_implications_for_the_origin_of_life.htm#B58">58</a>). Rapid incorporation of cytosine into a double-stranded replicator could best be achieved if all components (coding units and backbone) were synthesized under the same set of conditions, and polymer formation took place in the same environment. To avoid cytosine loss, this process should take at most several centuries at 25°C. A change in temperature would not improve matters unless it could be shown that the synthetic processes were retarded less, or enhanced more, than the degradative ones at a different temperature. </p> <p>Suitable chemistry for such transformations has not been demonstrated, however, and may not exist. The evidence that is available at the present time does not support the idea that RNA, or an alternative replicator that uses the current set of RNA bases, was present at the start of life. This conclusion could be reversed if a prebiotic simulation were devised that produced all of the bases in good yield under a single set of conditions, by using a plausible combination of water, atmospheric components, and minerals. In the absence of such a demonstration, more attention should be given to origin-of-life theories that do not require the four RNA bases: (<em>i</em>) The first living system used a replicator constructed of more accessible and stable components. A number of possibilities may exist, with the clay system of A.G. Cairns-Smith (<a href="http://www.biology-online.org/articles/references-prebiotic_cytosine_synthesis_a_critical_analysis_and_implications_for_the_origin_of_life.htm#B74">74</a>) perhaps the best known. (<em>ii</em>) Life began with cycles of autocatalytic reactions. Storage and transfer of information at the polymer level came later. A number of writers have discussed this possibility, including F. Dyson (<a href="http://www.biology-online.org/articles/references-prebiotic_cytosine_synthesis_a_critical_analysis_and_implications_for_the_origin_of_life.htm#B75">75</a>) and S. Kauffman (<a href="http://www.biology-online.org/articles/references-prebiotic_cytosine_synthesis_a_critical_analysis_and_implications_for_the_origin_of_life.htm#B76">76</a>). One possible system has been described in detail by G. Wächtershäuser (<a href="http://www.biology-online.org/articles/references-prebiotic_cytosine_synthesis_a_critical_analysis_and_implications_for_the_origin_of_life.htm#B77">77</a>). </p>
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