Evolutionary dynamics of CRISPR gene drives
Charleston Noble, Jason Olejarz, Kevin Esvelt, George Church, Martin Nowak
Abstract
The
alteration of wild populations has been discussed as a solution to a
number of humanity's most pressing ecological and public health
concerns. Enabled by the recent revolution in genome editing, CRISPR
gene drives, selfish genetic elements which can spread through
populations even if they confer no advantage to their host organism, are
rapidly emerging as the most promising approach. But before real-world
applications are considered, it is imperative to develop a clear
understanding of the outcomes of drive release in nature. Toward this
aim, we mathematically study the evolutionary dynamics of CRISPR gene
drives. We demonstrate that the emergence of drive-resistant alleles
presents a major challenge to previously reported constructs, and we
show that an alternative design which selects against resistant alleles
greatly improves evolutionary stability. We discuss all results in the
context of CRISPR technology and provide insights which inform the
engineering of practical gene drive systems.
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