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There is great interest in being able to spread beneficial traits throughout wild populations in ways that are self-sustaining. Here, we describe a chromosomal selfish genetic element, CleaveR [Cleave and Rescue (ClvR)], able to achieve this goal. ClvR comprises two linked chromosomal components. One, germline-expressed Cas9 and guide RNAs (gRNAs)-the Cleaver-cleaves and thereby disrupts endogenous copies of a gene whose product is essential. The other, a recoded version of the essential gene resistant to cleavage and gene conversion with cleaved copies-the Rescue-provides essential gene function. ClvR enhances its transmission, and that of linked genes, by creating conditions in which progeny lacking ClvR die because they have no functional copies of the essential gene. In contrast, those who inherit ClvR survive, resulting in an increase in ClvR frequency. ClvR is predicted to spread to fixation under diverse conditions. To test these predictions, we generated a ClvR element in Drosophila melanogasterClvRtko is located on chromosome 3 and uses Cas9 and four gRNAs to disrupt melanogaster technical knockout (tko), an X-linked essential gene. Rescue activity is provided by tko from Drosophila virilisClvRtko results in germline and maternal carryover-dependent inactivation of melanogaster tko (>99% per generation); lethality caused by this loss is rescued by the virilis transgene; ClvRtko activities are robust to genetic diversity in strains from five continents; and uncleavable but functional melanogaster tko alleles were not observed. Finally, ClvRtko spreads to transgene fixation. The simplicity of ClvR suggests it may be useful for altering populations in diverse species.
Pubmed ID: 30760597
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The MRC Laboratory of Molecular Biology (LMB) has long been, and remains, a world-class research laboratory. Our primary goal is to understand biological processes at the molecular level, through the application of methods drawn from physics, chemistry and genetics. This quest extends from structural studies of individual macromolecules, through their interactions and beyond to the functioning of subcellular systems, cells and multicellular systems in whole organisms, with the ultimate aim of using this knowledge to tackle specific problems in human health and disease. The LMB is one of the birthplaces of modern molecular biology. Many techniques were pioneered at the laboratory, most notably methods for determining the three-dimensional structure of proteins and DNA sequencing. Whole genome sequencing was initiated at the LMB. Another landmark discovery was the invention of monoclonal antibodies. Over the years, the work of LMB scientists has attracted 9 Nobel Prizes, shared between 13 LMB scientists, as well as numerous other prizes and scientific awards.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsCollects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.
View all literature mentionsDrosophila melanogaster with name y[1] M{w[+mC]=nos-Cas9.P}ZH-2A w[*] from BDSC.
View all literature mentions