The diversity reflects the 13,000-plus years of population history in the Americas, during which the founding Clovis-era population differentiated into hundreds of distinct regional populations, each with its own demographic history, its own patterns of genetic drift, its own episodes of bottleneck and expansion, and its own contacts and exchanges with neighboring populations.

The overall genetic structure of Native American populations reflects a founding event — the entry into the Americas from Beringia — followed by rapid differentiation into regional populations.

The differentiation has been shaped by the specific geographic patterns of the Clovis and post-Clovis expansions, by later migrations within the Americas (the Na-Dené-speaking peoples of the Pacific Northwest and interior, for example, are associated with a later migration from Asia), and by the subsequent demographic histories of populations in specific regions.

The genetic relationships among different Native American populations are an active area of research, and the availability of ancient genomes from different time periods and geographic locations — including the Anzick genome — has greatly enriched the understanding of these relationships.