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Biology subjects

Rochette, P.

Publications and source records attributed to Rochette, P..

2 recordsLinked to original sources

Evolutionary Advantage of Diversity-Generating Retroelements in Switching Environments

Diversity-Generating Retroelements (DGRs) create rapid, targeted variation within specific genomic regions in phages and bacteria. They operate through stochastic retro-transcription of a template region (TR) into a variable region (VR), which typically encodes ligand-binding proteins. Despite their prevalence, the conditions under which maintaining such hypermutating system is favorable remain unclear. Here we introduce a two-timescale framework separating fast VR diversification from slow TR evolution, allowing the dynamics of DGR-controlled loci to be analytically understood. Combining data analysis and analytical calculations we quantity the fitness gain provided by the diversification mechanism of DGR with respect to standard mutagenesis. Our framework accounts for observed patterns of DGR activity in human-gut Bacteroides and clarifies when constitutive DGR activation is evolutionarily favored.

evolutionary biology↗

Harnessing Diversity Generating Retroelements for in vivo targeted hyper-mutagenesis

The rapid evolution of novel functions requires targeted mutagenesis to avoid harmful mutations. Diversity-generating retroelements (DGRs) are natural systems that accelerate the evolution of diverse bacterial functions through targeted hypermutation. Here, we establish a method utilizing DGRs coupled to recombineering (DGRec), enabling the diversification of any sequence of interest in E. coli. DGRec can programmably diversify specific residues by leveraging the high error rate of the DGR reverse-transcriptase at adenines. We perform a detailed characterization of the reverse-transcriptase biases, highlighting how it maximizes the exploration of the sequence space while avoiding nonsense mutations. Applied to the phage {lambda} GpJ receptor binding domain, and to its lamB receptor, DGRec created diverse variants enabling E. coli to evade infection, and {lambda} to reinfect lamB mutants.

synthetic biology↗