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Letter
Nature Genetics  37, 1008 - 1011 (2005)
Published online: 28 August 2005; | doi:10.1038/ng1621

Real ribozymes suggest a relaxed error threshold

Ádám Kun1, 2, Mauro Santos3 & Eörs Szathmáry1, 2, 4

1  Collegium Budapest, Institute for Advanced Study, Szentháromság u. 2. Budapest H-1014, Hungary.

2  Department of Plant Taxonomy and Ecology, Eötvös University, Pázmány Péter sétány 1/C, Budapest H-1117, Hungary.

3  Departament de Genètica i de Microbiologia, Grup de Biologia Evolutiva, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

4  Research Group of Ecology and Theoretical Biology, Eötvös University, Hungarian Academy of Science, Pázmány Péter sétány 1/c, H-1117 Budapest, Hungary.

Correspondence should be addressed to Eörs Szathmáry szathmary@colbud.hu

The error threshold for replication, the critical copying fidelity below which the fittest genotype deterministically disappears, limits the length of the genome that can be maintained by selection. Primordial replication must have been error-prone, and so early replicators are thought to have been necessarily short1. The error threshold also depends on the fitness landscape. In an RNA world2, many neutral and compensatory mutations can raise the threshold, below which the functional phenotype3, rather than a particular sequence, is still present4, 5. Here we show, on the basis of comparative analysis of two extensively mutagenized ribozymes, that with a copying fidelity of 0.999 per digit per replication the phenotypic error threshold rises well above 7,000 nucleotides, which permits the selective maintenance of a functionally rich riboorganism6 with a genome of more than 100 different genes, the size of a tRNA. This requires an order of magnitude of improvement in the accuracy of in vitro−generated polymerase ribozymes7, 8. Incidentally, this genome size coincides with that estimated for a minimal cell achieved by top-down analysis9, omitting the genes dealing with translation.


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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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