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Novel Synthetic Medea Selfish Genetic Elements Drive Population Replacement in Drosophila; a Theoretical Exploration of Medea-Dependent Population Suppression

Akbari, Omar S. and Chen, Chun-Hong and Marshall, John M. and Huang, Haixia and Antoshechkin, Igor and Hay, Bruce A. (2014) Novel Synthetic Medea Selfish Genetic Elements Drive Population Replacement in Drosophila; a Theoretical Exploration of Medea-Dependent Population Suppression. ACS Synthetic Biology, 3 (12). pp. 915-928. ISSN 2161-5063. PMCID PMC3742681. doi:10.1021/sb300079h. https://resolver.caltech.edu/CaltechAUTHORS:20150204-092246509

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Abstract

Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/sb300079hDOIArticle
http://pubs.acs.org/doi/suppl/10.1021/sb300079hPublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742681PubMed CentralArticle
ORCID:
AuthorORCID
Akbari, Omar S.0000-0002-6853-9884
Antoshechkin, Igor0000-0002-9934-3040
Additional Information:© 2012 American Chemical Society. Received: August 30, 2012. Published: November 30, 2012. Special Issue: Design and Operation of Mammalian Cells. We would like to thank Lorain Schaeffer and Vijaya Kumar for help with library preparations and sequencing. This work was supported by grants to B.A.H. from the NIH (DP10D003878) and to J.M.M. from the Medical Research Council, U.K., and in part by a grant from the Foundation for the NIH through the Grand Challenges in Global Health initiative (Anthony A. James, PI, UC Irvine). Supplementary tables containing microRNA expression profiles for s14 ovary and 0−1 h embryo, top 20 miRNAs in s14 ovary, and top 20 miRNAs in 0−1 h embryo. The authors declare no competing financial interest
Funders:
Funding AgencyGrant Number
NIHDP10D003878
Medical Research Council (UK)UNSPECIFIED
NIH Grand Challenges in Global Health initiativeUNSPECIFIED
Subject Keywords:selfish genetic element; synthetic biology; maternal effect; gene drive; mosquito; dengue; malaria
Issue or Number:12
PubMed Central ID:PMC3742681
DOI:10.1021/sb300079h
Record Number:CaltechAUTHORS:20150204-092246509
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150204-092246509
Official Citation:Novel Synthetic Medea Selfish Genetic Elements Drive Population Replacement in Drosophila; a Theoretical Exploration of Medea-Dependent Population Suppression Omar S. Akbari, Chun-Hong Chen, John M. Marshall, Haixia Huang, Igor Antoshechkin, and Bruce A. Hay ACS Synthetic Biology 2014 3 (12), 915-928
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54360
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:04 Feb 2015 17:41
Last Modified:10 Nov 2021 20:32

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