Pervasive Suicidal Integrases in Deep-Sea Archaea

Catherine Badel (1) , Violette da Cunha (1) , Patrick Forterre (1) , Jacques Oberto (1)

1 I2BC - Institut de Biologie Intégrative de la Cellule

Mobile genetic elements (MGEs) often encode integrases which catalyze the site-specific insertion of their genetic information into the host genome and the reverse reaction of excision. Hyperthermophilic archaea harbor integrases belonging to the SSV-family which carry the MGE recombination site within their open reading frame. Upon integration into the host genome, SSV integrases disrupt their own gene into two inactive pseudogenes and are termed suicidal for this reason. The evolutionary maintenance of suicidal integrases, concurring with the high prevalence and multiples recruitments of these recombinases by archaeal MGEs, is highly paradoxical. To elucidate this phenomenon, we analyzed the wide phylogenomic distribution of a prominent class of suicidal integrases which revealed a highly variable integration site specificity. Our results highlighted the remarkable hybrid nature of these enzymes encoded from the assembly of inactive pseudogenes of different origins. The characterization of the biological properties of one of these integrases, Int pT26-2 showed that this enzyme was active over a wide range of temperatures up to 99 C and displayed a less-stringent site specificity requirement than comparable integrases. These observations concurred in explaining the pervasiveness of these suicidal integrases in the most hyperthermophilic organisms. The biochemical and phylogenomic data presented here revealed a target site switching system operating on highly thermostable integrases and suggested a new model for split gene reconstitution. By generating fast-evolving pseudogenes at high frequency, suicidal integrases constitute a powerful model to approach the molecular mechanisms involved in the generation of active genes variants by the recombination of proto-genes.

Mots clés: tyrosine recombinase; pseudogenes; evolution

Domaines: Biochimie, Biologie Moléculaire; Génétique

Catherine Badel, Violette da Cunha, Patrick Forterre, Jacques Oberto. Pervasive Suicidal Integrases in Deep-Sea Archaea. Molecular Biology and Evolution, 2020, 37, pp.1727 - 1743. ⟨10.1093/molbev/msaa041⟩. ⟨hal-02989989⟩