Abstract
Though pluripotency is well characterized in mammals, many questions remain to be resolved regarding its evolutionary history. A necessary prerequisite for addressing this issue is to determine the phylogenetic distributions and orthology relationships of the transcription factor families sustaining or modulating this property. In mammals, the NANOG homeodomain transcription factor is one of the core players in the pluripotency network. However, its evolutionary history has not been thoroughly studied, hindering the interpretation of comparative studies. To date, the NANOG family was thought to be monogenic, with numerous pseudogenes described in mammals, including a tandem duplicate in Hominidae. By examining a wide-array of craniate genomes, we provide evidence that the NANOG family arose at the latest in the most recent common ancestor of osteichthyans and that NANOG genes are frequently found as tandem duplicates in sarcopterygians and as a single gene in actinopterygians. Their phylogenetic distribution is thus reminiscent of that recently shown for Class V POU paralogues, another key family of pluripotency-controlling factors. However, while a single ancestral duplication has been reported for the Class V POU family, we suggest that multiple independent duplication events took place during evolution of the NANOG family. These multiple duplications could have contributed to create a layer of complexity in the control of cell competence and pluripotency, which could explain the discrepancies relative to the functional evolution of this important gene family. Further, our analysis does not support the hypothesis that loss of NANOG and emergence of the preformation mode of primordial germ cell specification are causally linked. Our study therefore argues for the need of further functional comparisons between NANOG paralogues, notably regarding the novel duplicates identified in sauropsids and non-eutherian mammals.
Highlights
In mammals, early embryonic cells are pluripotent as they can give rise to all embryonic cell lineages, but not to extra-embryonic tissues
A Blast-based approach followed by de novo gene prediction led to the identification of novel NANOG-like genes in the spotted gar (2), coelacanth (2), Indian python (1), American alligator (2), medium ground finch (2) and platypus genomes (1 novel and 1 already predicted)
These hypotheses had to be reevaluated in the light of more comprehensive understanding of the evolutionary histories of Class V POU genes [10,13]. These cases could serve as a warning that given the complexity of NANOG duplication patterns across vertebrates, and given the scarcity of functional data, it might be premature to draw conclusions about the causative role of those duplication events in relation to embryogenesis or germ line specification mode. Both Class V POU and NANOG genes were present in the genome of the common ancestor of extant osteichthyans and are often found as small two-member families in a given species
Summary
Early embryonic cells are pluripotent as they can give rise to all embryonic cell lineages, but not to extra-embryonic tissues. This property is maintained in cell lines derived from embryos (Embryonic Stem Cells, ESCs) or reprogrammed by various strategies (induced Pluripotent Stem Cells, iPSCs) [1,2]. Attempting to understand the extent to which the mammalian concept of pluripotency can be applied to other vertebrates is a classical problem of searching for homology, taking into account the fact that it could be uncoupled at different levels of biological organization [3]. A necessary step in this search for homology is the clarification of the evolutionary trajectories of the various molecular players implicated. Structural conservation does not imply functional conservation, but to carry out functional comparisons on a safe basis, knowledge of the evolutionary history of gene families is necessary
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