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

Abstract

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 >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.

Domestication of Crop Metabolomes: Desired and Unintended Consequences

“…Analysis of the Gephebase database also confirms that the largest majority of the mutations selected during the breeding process, both in animal and plants, are mostly loss-of-function mutations (nonsense, frameshift, or regulatory mutations abolishing gene expression). As such, the global view of evolution under crop diversification is consistent with fixation of large-effect loss-of-function mutations that generate evolutionary novelties in the human-controlled setting, but are then maladaptive under natural or highly variable environments [108]. This point aside, the database additionally contains several other metabolism-associated domestication genes of interest, including the BADH2 gene in rice, inactivation of which has been demonstrated to enrich aromatic properties [109].…”

The Tomato Interspecific NB-LRR Gene Arsenal and Its Impact on Breeding Strategies

“…As a consequence, a viable and alternative solution for designing resistant tomato varieties is the de novo domestication of wild species [82,83]. With a particular focus on the concept of signaling by cooperative assembly formation, it would be desirable to exploit the wild genetic background by going to edit only key domestication/improvement genes [83][84][85]. Indeed, the expansion of the pathogen sensor functionality can require to bring together a large number of actors that can be activated in a proximity-based manner resulting in a higher-magnitude signal [86].…”

A large deletion at the cortex locus eliminates butterfly wing patterning

“…In recent decades, the genetic basis of artificially selected variation has begun to be mapped in many organisms used in agriculture, floriculture and the pet trade, including the genetic mapping of a large number of genes responsible for flower color variation ( Park et al 2007 ; Giovannini et al 2021 ), melanin-based coat color in domestic mammals ( Cieslak et al 2011 ), plumage patterns, and colors in birds ( Domyan and Shapiro 2017 ; Price-Waldman and Stoddard 2021 ), and chromatophore distribution in squamates and fishes ( Guo et al 2021 ). These variants can affect genes involved in the enzymatic production, transport, and deposition of pigments such as the melanin and carotenoid pathways ( Mundy et al 2016 ; Courtier-Orgogozo and Martin 2020 ), or can be caused by genes that affect signaling or cell type differentiation [as with chromatophore distribution in squamates ( Kuriyama et al 2020 )]. The extensive set of artificial and domesticated genetic variants has been used repeatedly both for studies of genotype-to-phenotype relationship, and for understanding the genetics of disease states in humans ( Andersson 2016 ).…”