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DOI10.1073/pnas.2107413118
Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila
Oberhofer G.; Ivy T.; Hay B.A.
发表日期2021
ISSN0027-8424
卷号118期号:49
英文摘要One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and guide RNAs (gRNAs) to disrupt endogenous versions of an essential gene while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. As a consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition dependent, so too will be the survival of that population. To test this idea, we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23 °C, but when populations now dependent on Ts-ClvRdbe are shifted to 29 °C, death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in homing-based drive and to bring about suppression and/or killing of specific individuals in response to other stimuli. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Drosophila; Gene drive; Population suppression; Selfish genetic element
语种英语
scopus关键词CRISPR associated endonuclease Cas9; endonuclease; RNA; dbe protein, Drosophila; Drosophila protein; guide RNA; nuclear protein; allele; Article; controlled study; DNA strand breakage; Drosophila; essential gene; gene drive technology; gene function; gene locus; genetic variability; genotype; homologous recombination; lethality; nonhuman; RNA splicing; spermatogenesis; temperature dependence; temperature sensitivity; X chromosome; animal; biological model; CRISPR Cas system; Drosophila melanogaster; essential gene; gene drive technology; gene expression regulation; genetics; metabolism; physiology; population dynamics; procedures; temperature; transgene; Animals; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Drosophila melanogaster; Drosophila Proteins; Gene Drive Technology; Gene Expression Regulation; Genes, Essential; Models, Genetic; Nuclear Proteins; Population Control; RNA, Guide; Temperature; Transgenes
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/250945
作者单位Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, United States
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Oberhofer G.,Ivy T.,Hay B.A.. Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila[J],2021,118(49).
APA Oberhofer G.,Ivy T.,&Hay B.A..(2021).Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila.Proceedings of the National Academy of Sciences of the United States of America,118(49).
MLA Oberhofer G.,et al."Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila".Proceedings of the National Academy of Sciences of the United States of America 118.49(2021).
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