Extensive remodelling ofXISTregulatory networks during primate evolution

Abstract

AbstractUnravelling how gene regulatory networks are remodelled during evolution is crucial to understand how species adapt to environmental changes. We addressed this question for X-chromosome inactivation, a process essential to female development that is governed, in eutherians, by theXISTlncRNA and itscis-regulators. To reach high resolution, we studied closely related primate species, spanning 55 million years of evolution. We show that theXISTregulatory circuitry has diversified extensively over such evolutionary timeframe. The insertion of a HERVK transposon has reshuffledXIST3D interaction network in macaque embryonic stem cells (ESC) andXISTexpression is maintained by the additive effects of theJPXlncRNA gene and a macaque specific enhancer. In contrast,JPXis the main contributor toXISTexpression in human ESCs but is not significantly involved inXISTregulation in marmoset ESCs. None of these entities are however under purifying selection, which suggests that neutrally evolving non-coding elements harbour high adaptive potentials.