NANOGP1, a tandem duplicate of NANOG, exhibits partial functional conservation in human na?ve pluripotent stem cells

Gene duplication events can drive evolution by providing genetic material for new gene functions, and they create opportunities for diverse developmental strategies to emerge between species. To study the contribution of duplicated genes to human early development, we examined the evolution and function of NANOGP1, a tandem duplicate of the transcription factor NANOG. We found that NANOGP1 and NANOG have overlapping but distinct expression profiles, with high NANOGP1 expression restricted to early epiblast cells and naive-state pluripotent stem cells. Sequence analysis and epitope-tagging revealed that NANOGP1 is protein coding with an intact homeobox domain. The duplication that created NANOGP1 occurred earlier in primate evolution than previously thought and has been retained only in great apes, whereas Old World monkeys have disabled the gene in different ways, including homeodomain point mutations. NANOGP1 is a strong inducer of naive pluripotency; however, unlike NANOG, it is not required to maintain the undifferentiated status of human naive pluripotent cells. By retaining expression, sequence and partial functional conservation with its ancestral copy, NANOGP1 exemplifies how gene duplication and subfunctionalisation can contribute to transcription factor activity in human pluripotency and development.

Automated summary

Gene duplication events contribute to evolution by providing genetic material for new gene functions and allow for the emergence of diverse developmental strategies between species. NANOGP1, a tandem duplicate of the transcription factor NANOG, plays a role in human early development. NANOGP1 and NANOG exhibit overlapping but distinct expression patterns, with NANOGP1 primarily expressed in early epiblast cells and naive pluripotent stem cells.