The Coding Loci of Evolution and Domestication: Current Knowledge and Implications for Bio-Inspired Genome Editing

International audienceOne 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 get 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 >1,200 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 due to nonsense and frameshift mutations, represent a large fraction of the known loci of domestication (42% of identified coding mutations), compared to intraspecific (27%) and interspecific evolution (11%). While 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

Gene drive and its applications

Le forçage génétique est une nouvelle technique de manipulation génétique qui a été développée ces cinq dernières années et qui permet de propager rapidement des modifications génétiques dans les populations naturelles. Les applications potentielles sont nombreuses, à la fois en santé publique, en agriculture et en biologie de la conservation. Cet article présente les développements actuels de cette biotechnologie, ainsi que les enjeux et les risques qui y sont associés.Gene drive is a new genetic engineering technology that has been developed over the past five years and that allows genetic modifications to spread rapidly in natural populations. Potential applications are numerous, for public health issues, agriculture and conservation biology. This article presents the current developments in this biotechnology, as well as the issues and risks associated with it

Gephebase, a database of genotype-phenotype relationships for natural and domesticated variation in Eukaryotes

International audienceGephebase is a manually-curated database compiling our accumulated knowledge of the genes and mutations that underlie natural, domesticated and experimental phenotypic variation in all Eukaryotes-mostly animals, plants and yeasts. Gephebase aims to compile studies where the genotype-phenotype association (based on linkage mapping, association mapping or a candidate gene approach) is relatively well supported. Human clinical traits and aberrant mutant phenotypes in laboratory organisms are not included and can be found in other databases (e.g. OMIM, OMIA, Monarch Initiative). Gephebase contains more than 1700 entries. Each entry corresponds to an allelic difference at a given gene and its associated phenotypic change(s) between two species or two individuals of the same species, and is enriched with molecular details , taxonomic information, and bibliographic information. Users can easily browse entries and perform searches at various levels using boolean operators (e.g. transposable elements, snakes, carotenoid content , Doebley). Data is exportable in spreadsheet format. This database allows to perform meta-analyses to extract global trends about the living world and the research fields. Gephebase should also help breeders , conservationists and others to identify promising target genes for crop improvement, parasite/pest control, bioconservation and genetic diagnostic. It is freely available at www.gephebase.org

Drosophila Glue: A Promising Model for Bioadhesion

The glue produced by Drosophila larvae to attach themselves to a substrate for several days and resist predation until the end of metamorphosis represents an attractive model to develop new adhesives for dry environments. The adhesive properties of this interesting material have been investigated recently, and it was found that it binds as well as strongly adhesive commercial tapes to various types of substrates. This glue hardens rapidly after excretion and is made of several proteins. In D. melanogaster, eight glue proteins have been identified: four are long glycosylated mucoproteins containing repeats rich in prolines, serines and threonines, and four others are shorter proteins rich in cysteines. This protein mix is produced by the salivary glands through a complex packaging process that is starting to be elucidated. Drosophila species have adapted to stick to various substrates in diverse environmental conditions and glue genes appear to evolve rapidly in terms of gene number, number of repeats and sequence of the repeat motifs. Interestingly, besides its adhesive properties, the glue may also have antimicrobial activities. We discuss future perspectives and avenues of research for the development of new bioadhesives mimicking Drosophila fly glue

The Coding Loci of Evolution and Domestication: Current Knowledge and Implications for Bio-Inspired Genome Editing

International audienceOne 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 get 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 >1,200 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 due to nonsense and frameshift mutations, represent a large fraction of the known loci of domestication (42% of identified coding mutations), compared to intraspecific (27%) and interspecific evolution (11%). While 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

Using CRISPR ‐based gene drive for agriculture pest control

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Can a Population Targeted by a CRISPR-Based Homing Gene Drive Be Rescued?

CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations. This technique is based on the release of individuals carrying an engineered piece of DNA that can be preferentially inherited by the progeny. The development of countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals carrying a brake construct that targets and inactivates the drive allele but leaves the wild-type allele unaffected. Here we develop models to investigate the efficiency of such brakes. We consider a variable population size and use a combination of analytical and numerical methods to determine the conditions where a brake can prevent the extinction of a population targeted by an eradication drive. We find that a brake is not guaranteed to prevent eradication and that characteristics of both the brake and the drive affect the likelihood of recovering the wild-type population. In particular, brakes that restore fitness are more efficient than brakes that do not. Our model also indicates that threshold-dependent drives (drives that can spread only when introduced above a threshold) are more amenable to control with a brake than drives that can spread from an arbitrary low introduction frequency (threshold-independent drives). Based on our results, we provide practical recommendations and discuss safety issues

Male genital lobe morphology affects the chance to copulate in <i>Drosophila pachea</i>

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Male genital lobe morphology affects the chance to copulate in <i>Drosophila pachea</i>

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Higher evolutionary dynamics of gene copy number for Drosophila glue genes located near short repeat sequences

Abstract Background During evolution, genes can experience duplications, losses, inversions and gene conversions. Why certain genes are more dynamic than others is poorly understood. Here we examine how several Sgs genes encoding glue proteins, which make up a bioadhesive that sticks the animal during metamorphosis, have evolved in Drosophila species. Results We examined high-quality genome assemblies of 24 Drosophila species to study the evolutionary dynamics of four glue genes that are present in D. melanogaster and are part of the same gene family - Sgs1, Sgs3, Sgs7 and Sgs8 - across approximately 30 millions of years. We annotated a total of 102 Sgs genes and grouped them into 4 subfamilies. We present here a new nomenclature for these Sgs genes based on protein sequence conservation, genomic location and presence/absence of internal repeats. Two types of glue genes were uncovered. The first category (Sgs1, Sgs3x, Sgs3e) showed a few gene losses but no duplication, no local inversion and no gene conversion. The second group (Sgs3b, Sgs7, Sgs8) exhibited multiple events of gene losses, gene duplications, local inversions and gene conversions. Our data suggest that the presence of short “new glue” genes near the genes of the latter group may have accelerated their dynamics. Conclusions Our comparative analysis suggests that the evolutionary dynamics of glue genes is influenced by genomic context. Our molecular, phylogenetic and comparative analysis of the four glue genes Sgs1, Sgs3, Sgs7 and Sgs8 provides the foundation for investigating the role of the various glue genes during Drosophila life