Nuku, a family of primate retrocopies derived from KU70
| Autor: | Jagdish Suresh Patel, Paul A. Rowley, James T. Van Leuven, Aisha Ellahi, Sara L. Sawyer, Kyudong Han |
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| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI01140
Primates retrocopy AcademicSubjects/SCI00010 Retrotransposon QH426-470 Biology AcademicSubjects/SCI01180 medicine.disease_cause Evolution Molecular 03 medical and health sciences 0302 clinical medicine Gene Duplication Genetics medicine Animals Ku70 RNA Messenger Molecular Biology Gene NHEJ Genetics (clinical) 030304 developmental biology Investigation 0303 health sciences Mutation Intron Translation (biology) Evolutionary biology AcademicSubjects/SCI00960 Neofunctionalization 030217 neurology & neurosurgery Functional divergence |
| Zdroj: | G3: Genes|Genomes|Genetics G3: Genes, Genomes, Genetics, Vol 11, Iss 8 (2021) |
| ISSN: | 2160-1836 |
| Popis: | The gene encoding 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. |
| Databáze: | OpenAIRE |
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