Thesis Defense : Quynh-Huong LAI « Coevolution and functional diversification of the TRF2-Apollo interaction in jawed vertebrates »

Thesis director : Marie-Josèphe GIRAUD PANIS

Abstract : Telomere repeat-binding factor 2 (TRF2) recruits the 5′ exonuclease Apollo through its TRFH domain, a step required for telomere-end processing and for the formation of the protective 3′ G-overhang. However, the evolutionary conservation and functional variation of this interaction across vertebrates remain poorly understood. Here, we combined comparative sequence, mirror-tree coevolution and selection analyses with in vitro interaction assays to examine the evolution of the TRF2-Apollo pair in jawed vertebrates. TRF2 and Apollo showed correlated evolutionary rates, most markedly between the TRF2 TRFH domain and the Apollo C-terminal region, a pattern compatible with coadaptation of the interaction interface. The canonical Apollo YxLxP docking motif and key TRF2 docking residues are conserved in sauropsids and mammals but more variable in fishes, amphibians, and chondrichthyans. Far-western and co-immunoprecipitation assays revealed marked interspecies variation in interaction strength, with a particularly strong interaction in the turquoise killifish. In a comparative analysis of 15 species, binding strength was negatively associated with age at sexual maturity, an association compatible with a greater requirement for this interaction in fast-developing animals. In the turquoise killifish, telomeric G-overhang abundance remained stable across age groups, although whether this stability is causally related to the strong TRF2-Apollo interaction remains to be tested.