Previous comparisons of modern maternal genetic lineages with those obtained from Early and Middle Horizon burial sites suggested population discontinuity in the Central Valley. This result was interpreted as support for a later Penutian expansion. This study re-addresses the question of biological continuity in the Central Valley with more modern samples and attention to genetic variants that offer higher resolution. Ample evidence of biological continuity in the Central Valley is found. This includes evidence of a Yok-Utian population expansion. The estimated timing of this population expansion is consistent with the estimated time depth of the Yok-Utian language family and the appearance of the Early Horizon in the archaeological record. The inclusion of ancient and modern genetic samples from the Columbia Plateau and Great Basin, motivated by evidence of cultural ties between these regions and the Central Valley, supports the hypothesis that the northwest Great Basin may have played a pivotal role in the spread of both genes and culture in the West.