Not so pseudo - functional conservation of human NANOGP1

Gene duplication is an important driver of evolution and the emergence of novel gene functions. These so-called pseudogenes offer insights into evolutionary developmental events between species. However, pseudogenes are often redundant or dysfunctional and thus their contribution to development is debated. In this study, Peter Rugg-Gunn and colleagues investigate NANOGP1, a tandem duplicate of the human transcription factor NANOG, to study the contribution of duplicated genes to early human development. Using naïve human pluripotent stem cells (hPSCs), the authors show that NANOGP1 shares 97% homology with NANOG and has overlapping but distinct expression profiles. Despite their similarity, functional differences are notable; although both are inducers of naïve pluripotency in hPSCs, NANOGP1 (unlike NANOG) is not required to maintain their undifferentiated status. Interestingly, by searching for gene matches with human NANOGP1 in non-human primates, the authors also find that the duplication event that created NANOGP1 occurred earlier in primate evolution than previously thought and has only been retained in great apes, whereas the gene is functionally disabled in Old World monkeys. In conclusion, this study shows that NANOGP1 has retained partial functional conservation with NANOG, highlighting the role of gene duplication and sub-functionalisation on human pluripotency and development. Furthermore, this study lays the foundations for NANOGP1 to be re-classified as a protein-coding gene, rather than a pseudogene.