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One promising application of CRISPR/Cas9 is to create targeted mutations to introduce traits of interest into domesticated organisms. However, a major current limitation for crop and livestock improvement is to identify the precise genes and genetic changes that must be engineered to obtain traits of interest. Here, we discuss the advantages of bio-inspired genome editing, i.e. the engineered introduction of natural mutations that have already been associated with traits of interest in other lineages (breeds, populations or species). To obtain a landscape view of potential targets for genome editing, we used Gephebase (www.gephebase.org), a manually curated database compiling published data about the genes responsible for evolutionary and domesticated changes across eukaryotes, and examined the &gt;1200 mutations that have been identified in the coding regions of more than 700 genes in animals, plants and yeasts. We observe that our genetic knowledge is relatively important for certain traits, such as xenobiotic resistance, and poor for others. We also note that protein-null alleles, often owing to nonsense and frameshift mutations, represent a large fraction of the known loci of domestication (42% of identified coding mutations), compared with intraspecific (27%) and interspecific evolution (11%). Although this trend may be subject to detection, publication and curation biases, it is consistent with the idea that breeders have selected large-effect mutations underlying adaptive traits in specific settings, but that these mutations and associated phenotypes would not survive the vagaries of changing external and internal environments. Our compilation of the loci of evolution and domestication uncovers interesting options for bio-inspired and transgene-free genome editing.

The coding loci of evolution and domestication: current knowledge and implications for bio-inspired genome editing