Studies of the peopling of the Americas have focused on the timing and number of initial migrations. Less attention has been paid to the subsequent spread of people within the Americas. We sequenced 15 ancient human genomes spanning from Alaska to Patagonia; six are ≥10,000 years old (up to ~18× coverage). All are most closely related to Native Americans, including those from an Ancient Beringian individual and two morphologically distinct “Paleoamericans.” We found evidence of rapid dispersal and early diversification that included previously unknown groups as people moved south. This resulted in multiple independent, geographically uneven migrations, including one that provides clues of a Late Pleistocene Australasian genetic signal, as well as a later Mesoamerican-related expansion. These led to complex and dynamic population histories from North to South America.

The Caribbean was one of the last regions of the Americas to be settled by humans, but how, when, and from where they reached the islands remains unclear. We generated genome-wide data for 93 ancient Caribbean islanders dating between 3200-400 cal. BP and find evidence of at least three separate dispersals into the region, including two early dispersals into the Western Caribbean, one of which seems connected to radiation events in North America. This was followed by a later expansion from South America. We also detect genetic differences between the early settlers and the newcomers from South America with almost no evidence of admixture. Our results add to our understanding of the initial peopling of the Caribbean and the movements of Archaic Age peoples in the Americas.

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record. This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.