Endogenous generation of genomic diversity through reverse transcription and homologous recombination.

Abstract: It is commonly believed that organisms diversify their genomes 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—focusing variation on functionally relevant regions and improving the efficiency of genomic exploration. 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 hypothesize that transcribed pseudogenes and duplicated sequences 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 [3], DGbyRT is presented as a regulated, context-sensitive diversification strategy. As RNA-based technologies advance, understanding natural reverse transcription mechanisms becomes increasingly relevant to both evolutionary biology and therapeutic innovation.