During this period of isolation, according to the hypothesis, the ancestral Native American population would have been accumulating genetic variants that differentiated it from its Asian source population — developing the specific genetic profile that characterizes all Native American populations and that distinguishes them from the Asian populations most closely related to them.

The long isolation in Beringia is proposed as the explanation for why Native American genetic profiles are distinct from those of any existing Asian population — because the Beringian population was separated from Asia long enough to diverge genetically before dispersing into the Americas.

The hypothesis was initially proposed on genetic grounds, based on the observed genetic diversity of Native American populations and models of how long genetic divergence of the observed magnitude would require.

The genetic evidence suggested that the founding Native American population had been isolated for roughly 10,000 years before the dispersal into the Americas — and the location most consistent with that isolation, given the subsequent dispersal into the Americas from the north, was Beringia.