Far northeastern Siberia has been occupied by humans for more than 40 thousand

years. Yet, owing to a scarcity of early archaeological sites and human remains, its

population history and relationship to ancient and modern populations across Eurasia

and the Americas are poorly understood. Here, we analyze 34 ancient genome

sequences, including two from fragmented milk teeth found at the ~31.6 thousand-yearold (kya) Yana RHS site, the earliest and northernmost Pleistocene human remains

found. These genomes reveal complex patterns of past population admixture and

replacement events throughout northeastern Siberia, with evidence for at least three

large-scale human migrations into the region. The first inhabitants, a previously

unknown population of “Ancient North Siberians” (ANS), represented by Yana RHS,

diverged ~38 kya from Western Eurasians, soon after the latter split from East Asians.

Between 20 and 11 kya, the ANS population was largely replaced by peoples with

ancestry related to present-day East Asians, giving rise to ancestral Native Americans

and “Ancient Paleosiberians” (AP), represented by a 9.8 kya skeleton from Kolyma

River. AP are closely related to the Siberian ancestors of Native Americans, and

ancestral to contemporary communities such as Koryaks and Itelmen. Paleoclimatic

modelling shows evidence for a refuge during the last glacial maximum (LGM) in

southeastern Beringia, suggesting Beringia as a possible location for the admixture

forming both ancestral Native Americans and AP. Between 11 and 4 kya, AP were in

turn largely replaced by another group of peoples with ancestry from East Asia, the

“Neosiberians” from which many contemporary Siberians derive. We detect gene flow

events in both directions across the Bering Strait during this time, influencing the

genetic composition of Inuit, as well as Na Dene-speaking Northern Native Americans,

whose Siberian-related ancestry components is closely related to AP. Our analyses

reveal that the population history of northeastern Siberia was highly dynamic

throughout the Late Pleistocene and Holocene. The pattern observed in northeastern

Siberia, with earlier, once widespread populations being replaced by distinct peoples,

seems to have taken place across northern Eurasia, as far west as Scandinavia.