Native American admixture recapitulates population-specific migration and settlement of the continental United States

European and African descendants settled the continental US during the 17th-19th centuries, coming into contact with established Native American populations. The resulting admixture among these groups yielded a significant reservoir of Native American ancestry in the modern US population. We analyzed the patterns of Native American admixture seen for the three largest genetic ancestry groups in the US population: African descendants, Western European descendants, and Spanish descendants. The three groups show distinct Native American ancestry profiles, which are indicative of their historical patterns of migration and settlement across the country. Native American ancestry in the modern African descendant population does not coincide with local geography, instead forming a single group with origins in the southeastern US, consistent with the Great Migration of the early 20th century. Western European descendants show Native American ancestry that tracks their geographic origins across the US, indicative of ongoing contact during westward expansion, and Native American ancestry can resolve Spanish descendant individuals into distinct local groups formed by more recent migration from Mexico and Puerto Rico. We found an anomalous pattern of Native American ancestry from the US southwest, which most likely corresponds to the Nuevomexicano descendants of early Spanish settlers to the region. We addressed a number of controversies surrounding this population, including the extent of Sephardic Jewish ancestry. Nuevomexicanos are less admixed than nearby Mexican-American individuals, with more European and less Native American and African ancestry, and while they do show demonstrable Sephardic Jewish ancestry, the fraction is no greater than seen for other New World Spanish descendant populations.Author summary: The post-Colombian settling of North America brought African, European, and Native American populations into close proximity for the first time. The inevitable admixture among these groups resulted a reservoir of Native American ancestry in modern US populations, outside of traditional Native American groups. Here we characterize that Native American ancestry in a geographically diverse set of African descendant, Western European descendant, and Spanish descendant populations. We show that Native American ancestry in the US population is not monomorphic, strongly related to geography, and suggestive of frequent historical admixture between European settlers and local Native American groups. We also show the presence of a unique, admixed Spanish population in the Southwestern US, the modern Nuevomexicanos, that is distinct from other Spanish descendant groups.