The genetic legacy of the 17th-century colonial capital of St. Mary's City.

Founded in 1634, St. Mary's City was the first English settlement in the colony of Maryland. Despite existing written records and the ability of many present-day Americans to trace their ancestry to the historic city, substantial gaps remain in our knowledge of this early founder population. To address these gaps, we analyzed the genomes of 49 individuals from 17th-century St. Mary's City to trace their genetic ancestry, examine their enduring legacy, and demonstrate the efficacy of using an identity-by-descent (IBD) approach to link historical individuals to the present. In our analysis, we identified over 1.3 million genetic relatives of the St. Mary's individuals among research participants in the 23andMe Research Institute's database. We found high rates of genetic sharing with participants from western England and Wales, suggesting a likely place of origin for many of the colonial city's earliest inhabitants. Additionally, we observed strong genetic connections with participants from Kentucky, mirroring a recorded post-Revolutionary War migration of Maryland Catholics to that region. By further integrating genealogical information from present-day research participants who share the closest genetic connections to the St. Mary's individuals, we propose possible identities for three sequenced historical St. Mary's City residents, including Thomas Greene, the second governor of the colony of Maryland. This unique case study highlights the power of genetics to restore lost identities and reconstruct historical relationships by tracing geographic signals of ancestry. VIDEO ABSTRACT.