Figure 3.

PIKKs Evolved before the Diversification of Eukaryotes and Remain Conserved in Most Lineages

A representative sampling of eukaryotic lineages, including species in the supergroups Amorpheae (Amoebozoa + fungi + animals), Archaeplastida (green algae + land plants), TSAR (Telonemia + stramenopiles + alveolates + Rhizaria), and Excavata, is shown to illustrate the evolution of PIKKs and select associated proteins discussed in the text. All five major PIKKs (TOR, ATM, DNA-PK, SMG1, and ATR) likely evolved before the unicellular last eukaryotic common ancestor. RAPTOR and LST8, key components of TORC1, also evolved early in eukaryotes. TRRAP, a noncatalytic PIKK-like protein, probably evolved later but before the divergence of Amorpheae and Archaeplastida + TSAR. TORC2 and Sestrins evolved in Amorpheae, and p53 evolved from p53-like genes to sense cellular stress in animals. PIKKs are conserved in most lineages, although some branches have lost specific PIKKs, as shown here. Parasitic lineages are an exception that have lost multiple PIKKs, such as Plasmodium (in the TSAR supergroup), which does not encode any PIKKs, and Giardia (in the Excavata supergroup), which only encodes TOR.