Pluripotency and the endogenous retrovirus HERVH: conflict or serendipity?

Remnants of ancient retroviral infections during evolution litter all mammalian genomes. In modern humans, such endogenous retroviral (ERV) sequences comprise at least 8% of the genome. While ERVs and other types of transposable elements undoubtedly contribute to the genomic "junk yard", functions for some ERV sequences have been demonstrated, with growing evidence that ERVs can be important players in gene regulatory processes. Here we focus on one particular large family of human ERVs, termed HERVH, which several recent studies suggest has a key regulatory role in human pluripotent stem cells. Remarkably, this is not the first instance of an ERV controlling pluripotency. We speculate as to why this convergent evolution might have come about, suggesting that it may reflect selection on the virus to extend the time available for transposition. Alternatively it may reflect serendipity alone. Our genome harbors ∼2000 copies of the retroviral element HERVH, which have accumulated by infections and retrotranspositions over time. This endogenization process resulted in some HERVH copies acquiring a domesticated cellular function. In primates, HERVH drives a regulatory network modulating pluripotency. We ask why similar events occur repeatedly during evolution.