Nuku, a family of primate retrocopies derived from KU70

Abstract

The ubiquitous DNA repair protein, Ku70p, has undergone extensive copy number expansion during primate evolution. Gene duplications of KU70 have the hallmark of long interspersed element-1 mediated retrotransposition with evidence of target-site duplications, the poly-A tails, and the absence of introns. Evolutionary analysis of this expanded family of KU70-derived “NUKU” retrocopies reveals that these genes are both ancient and also actively being created in extant primate species. NUKU retrocopies show evidence of functional divergence away from KU70, as evinced by their altered pattern of tissue expression and possible tissue specific translation. Molecular modeling predicted that amino acid changes in Nuku2p at the interaction interface with Ku80p would prevent the assembly of the Ku heterodimer. The lack of Nuku2p-Ku80p interaction was confirmed by yeast two-hybrid assay, which contrasts the robust interaction of Ku70p-Ku80p. While several NUKU retrocopies appear to have been degraded by mutation, NUKU2 shows evidence of positive natural selection, suggesting that this retrocopy is undergoing neofunctionalization. Although Nuku proteins do not appear to antagonize retrovirus transduction in cell culture, the observed expansion and rapid evolution of NUKUs could be being driven by alternative selective pressures related to infectious disease or an undefined role in primate physiology.

Recurrent Duplication and Diversification of a Vital DNA Repair Gene Family Across Drosophila

“…Despite the essentiality and deep conservation of eukaryotic DNA repair pathways, many DNA repair proteins are unconserved. These repair proteins evolve rapidly under positive selection, resulting in highly divergent alleles between closely related species of yeast ( Sawyer and Malik 2006 ; Rowley et al 2021 ), plants ( Zhang et al 2019 , 2023 ), flies ( Lee et al 2016 ), fish ( Kolora et al 2021 ), frogs ( Sun et al 2018 ), and primates ( Demogines et al 2010 ; Lou et al 2014 , 2016 ). This rapid evolution has been attributed largely to extreme environments and viral pathogens; however, building literature implicates rapidly evolving DNA repeats as dynamic substrates that select for innovation of DNA repair proteins ( Brand and Levine 2021 ).…”

Recurrent duplication and diversification of a vital DNA repair gene family across Drosophila

“…Despite the essentiality and deep conservation of eukaryotic DNA repair, many DNA repair proteins are unconserved. These repair proteins evolve rapidly under positive selection, resulting in highly divergent alleles between closely related species (Sawyer and Malik 2006; Demogines, et al 2010; Lou, et al 2014; Lee, et al 2016; Lou, et al 2016; Sun, et al 2018; Zhang, et al 2019; Kolora, et al 2021; Rowley, et al 2021; Zhang, et al 2023). This rapid evolution has been attributed largely to extreme environments and viral pathogens; however, a building literature implicates rapidly evolving DNA repeats as dynamic substrates that select for innovation of DNA repair proteins (Brand and Levine 2021).…”