Evolutionary history of the DNA repair protein, Ku, in eukaryotes and prokaryotes

Abstract

Abstract Background The DNA end-joining protein, Ku, is essential in non-homologous end joining in prokaryotes and eukaryotes. It was first discovered in eukaryotes and later by PSI blast, in prokaryotes. While Ku in eukaryotes is often a multi-domain protein functioning in DNA repair of physiological and pathological DNA double-stranded breaks, Ku in prokaryotes is a single-domain protein functioning in pathological DNA repair in spores or late stationary phase. In this paper, we have attempted to systematically search for Ku protein in different phyla of bacteria and archaea as well as in different groups of eukarya. Result From our search of 122 sequenced bacterial genomes using NCBI BLASTP, only 31 genomes yielded at least one Ku sequence. In eukarya, we found Ku protein in 27 out of 59 species using BLASTP in NCBI. Since the entire genome of all eukaryotic species is not fully sequenced this number could go up. From a comprehensive search of all OrthoDB archaeal genomes, we received a positive hit in 19 specific archaeal species that possessed Ku70/80 beta-barrel domain. Likewise, we retrieved 11 viral sequences consisting of the Ku70/80 beta-barrel domain using a comprehensive search against virus genomes in OrthoDB. We then drew a phylogenetic maximum likelihood tree to determine the ancestral relationship between Ku70 and Ku80 in eukaryotes and Ku in bacteria, archaea, and viruses. Our tree revealed a common node for some Ku, Ku70, and Ku80. Among the three forms of Ku, Ku70 showed the highest sequence divergence. Conclusion One model proposed for Ku evolution hypothesizes that Ku70 arose first and duplicated to form Ku80. Ku70 or Ku80 horizontally transferred onto archaea and then onto bacteria to give the present forms of Ku in three domains of life. Additionally, we analyzed the domains of the different eukaryotic species to demonstrate that fusion, terminal addition, terminal deletion, single domain loss, and single domain emergence events during evolution.