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TF-High-Evolutionary: In Vivo Mutagenesis of Gene Regulatory Networks for the Study of the Genetics and Evolution of the Drosophila Regulatory Genome.


ABSTRACT: Understanding the evolutionary potential of mutations in gene regulatory networks is essential to furthering the study of evolution and development. However, in multicellular systems, genetic manipulation of regulatory networks in a targeted and high-throughput way remains challenging. In this study, we designed TF-High-Evolutionary (HighEvo), a transcription factor (TF) fused with a base editor (activation-induced deaminase), to continuously induce germline mutations at TF-binding sites across regulatory networks in Drosophila. Populations of flies expressing TF-HighEvo in their germlines accumulated mutations at rates an order of magnitude higher than natural populations. Importantly, these mutations accumulated around the targeted TF-binding sites across the genome, leading to distinct morphological phenotypes consistent with the developmental roles of the tagged TFs. As such, this TF-HighEvo method allows the interrogation of the mutational space of gene regulatory networks at scale and can serve as a powerful reagent for experimental evolution and genetic screens focused on the regulatory genome.

SUBMITTER: Li XC 

PROVIDER: S-EPMC11342961 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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TF-High-Evolutionary: In Vivo Mutagenesis of Gene Regulatory Networks for the Study of the Genetics and Evolution of the Drosophila Regulatory Genome.

Li Xueying C XC   Srinivasan Vani V   Laiker Ian I   Misunou Natalia N   Frankel Nicolás N   Pallares Luisa F LF   Crocker Justin J  

Molecular biology and evolution 20240801 8


Understanding the evolutionary potential of mutations in gene regulatory networks is essential to furthering the study of evolution and development. However, in multicellular systems, genetic manipulation of regulatory networks in a targeted and high-throughput way remains challenging. In this study, we designed TF-High-Evolutionary (HighEvo), a transcription factor (TF) fused with a base editor (activation-induced deaminase), to continuously induce germline mutations at TF-binding sites across  ...[more]

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