PerspectiveMolecular Biology

Harnessing mutation: The best of two worlds

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Science  16 Sep 2016:
Vol. 353, Issue 6305, pp. 1206-1207
DOI: 10.1126/science.aai8233

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Summary

Rapid evolution requires high rates of mutation that come at the cost of reduced viability. This is true at the single-cell level in bacteria as well as in the highest complex vertebrates. Immunity relies on rapid evolution to enhance the recognition of external threats and to neutralize them, often by inflicting damage to the genomes of potentially harmful invaders. On page 1248 of this issue, Nishida et al. (1) report combining a polynucleotide cytosine deaminase (PmCDA1)—an enzyme involved in antigen receptor diversification in vertebrates—with the bacterial immune restriction system clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 to enhance point mutation with almost single-nucleotide precision to levels that, if occurring genome-wide, would otherwise result in lethality. With localized mutagenesis, also achieved through a similar approach by Komor et al. (2), comes the promise of gene correction by means of targeted editing. Both studies show that not only is targeted mutation feasible but that its efficiency, and even the type of mutation, can be driven by manipulating or engaging the various cellular pathways involved in repairing edited bases.