Activation of r²⁰-dependent recombination and horizontal gene transfer in Mycoplasma genitalium

© The Author(s) 2018. In the human pathogen Mycoplasma genitalium, homologous recombination is under the control of r20, an alternative sigma factor that boosts the generation of genetic and antigenic diversity in the population. Under laboratory growth conditions, r20 activation is rare and the factors governing its intermittent activity are unknown. Two r20-regulated genes, rrlA and rrlB, showed to be important for recombination of homologous DNA sequences in this bacterium. Herein, we demonstrate that rrlA and rrlB code for two small proteins that participate in a feed-forward loop essential for r20 function. In addition, we identify novel genes regulated by r20 and show that several non-coding regions, which function as a reservoir for the generation of antigenic diversity, are also activated by this alternative sigma factor. Finally, we reveal that M. genitalium cells can transfer DNA horizontally by a novel mechanism that requires RecA and is facilitated by r20 overexpression. This DNA transfer system is arguably fundamental for persistence of M. genitalium within the host since it could facilitate a rapid dissemination of successful antigenic variants within the population. Overall, these findings impose a novel conception of genome evolution, genetic variation and survival of M. genitalium within the host.