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<p>It is commonly believed that organisms diversify their genomes primarily through point mutations, insertions, and deletions. Here, I propose a complementary mechanism: Diversity Generation by Reverse Transcriptase (DGbyRT), in which cellular or exogenous RNAs are reverse transcribed into cDNA and integrated into the genome via homology-directed recombination. This process enables the reuse of modular genetic information—derived from both coding and non-coding transcripts—thereby biasing variation toward regions already represented in the transcriptome and potentially altering the statistical distribution of the explored sequence space. DGbyRT draws on mechanisms observed across life, including diversity-generating retroelements, retrotransposons, telomerase, and somatic hypermutation, and may involve endogenous RTs such as Pol-θ. I hypothesise that transcribed pseudogenes and duplicated sequences may serve as reservoirs for recombinable modules. DGbyRT may also contribute to somatic-to-germline communication, with reverse-transcribed RNAs crossing the Weismann barrier to influence heritable change. Inspired by synthetic biology tools such as the AutoDiMe method, DGbyRT is presented as a context-dependent diversification mechanism whose frequency may be modulated by cellular regulation of reverse transcriptase activity. As RNA-based technologies advance, understanding natural reverse transcription becomes increasingly relevant to both evolutionary biology and therapeutic innovation.</p>

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RNA-templated diversity generation via reverse transcription and homologous recombination: an evolutionary hypothesis

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Matteo G. E. Mariani

摘要

It is commonly believed that organisms diversify their genomes primarily through point mutations, insertions, and deletions. Here, I propose a complementary mechanism: Diversity Generation by Reverse Transcriptase (DGbyRT), in which cellular or exogenous RNAs are reverse transcribed into cDNA and integrated into the genome via homology-directed recombination. This process enables the reuse of modular genetic information—derived from both coding and non-coding transcripts—thereby biasing variation toward regions already represented in the transcriptome and potentially altering the statistical distribution of the explored sequence space. DGbyRT draws on mechanisms observed across life, including diversity-generating retroelements, retrotransposons, telomerase, and somatic hypermutation, and may involve endogenous RTs such as Pol-θ. I hypothesise that transcribed pseudogenes and duplicated sequences may serve as reservoirs for recombinable modules. DGbyRT may also contribute to somatic-to-germline communication, with reverse-transcribed RNAs crossing the Weismann barrier to influence heritable change. Inspired by synthetic biology tools such as the AutoDiMe method, DGbyRT is presented as a context-dependent diversification mechanism whose frequency may be modulated by cellular regulation of reverse transcriptase activity. As RNA-based technologies advance, understanding natural reverse transcription becomes increasingly relevant to both evolutionary biology and therapeutic innovation.