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Mutational Robustness of Ribosomal Protein Genes

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Science  05 Nov 2010:
Vol. 330, Issue 6005, pp. 825-827
DOI: 10.1126/science.1194617

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Keeping Fit

Mutations may be deleterious, neutral, or advantageous. Understanding the relative effect of a new mutation on an organism's fitness is important for many systems from complex diseases to conservation biology. Lind et al. (p. 825) used the bacterium Salmonella typhimurium to study the effects of random mutations in two ribosomal proteins on fitness. Most mutations, whether synonymous or nonsynonymous, had significant fitness costs, thus overturning the prevailing dogma that most point mutations are either neutral or lethal and indicating that the mutations influenced messenger RNA structure and/or stability.

Abstract

The distribution of fitness effects (DFE) of mutations is of fundamental importance for understanding evolutionary dynamics and complex diseases and for conserving threatened species. DFEs estimated from DNA sequences have rarely been subject to direct experimental tests. We used a bacterial system in which the fitness effects of a large number of defined single mutations in two ribosomal proteins were measured with high sensitivity. The obtained DFE appears to be unimodal, where most mutations (120 out of 126) are weakly deleterious and the remaining ones are potentially neutral. The DFEs for synonymous and nonsynonymous substitutions are similar, suggesting that in some genes, strong fitness constraints are present at the level of the messenger RNA.

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