Evidence of non-random mutation rates suggests an evolutionary risk management strategy

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Martincorena et al are reporting in Nature evidence challenging the tenet that mutations occur randomly and then selection governs whether they are fixed or not. By comparing 34 E.coli genomes  and after excluding usual causes of difference in mutation rate (codon usage bias, mRNA-folding stability in the 5´, GC content and within-species homologous recombination)  the authors observe that the neutral mutation rate varies by more than an order of magnitude across 2.659 genes. The mutation rate is lower at highly expressed genes implying the presence of unknown compensatory mechanisms. They go a step further showing that purifying, rather than positive, selection has driven the evolution of the local point mutation rate in order to reduce risk of deleterious mutations and possibly increase the rate of non-deleterious mutations thus increasing the adaptive potential.

Periklis Makrythanasis, MD, PhD

Martincorena I, Seshasayee AS, Luscombe NM.; Nature. 2012 Apr 22. doi: 10.1038/nature10995. [Epub ahead of print]

OMMBID Chapter 13: The Nature and Mechanisms of Human Gene Mutation

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