Whole-genome history and evolution in a thousand ancient Britons (360G-Wellcome-217223_Z_19_Z)

On the cusp of the era of precision medicine, data from the British population comprise the world’s most well-characterized resource linking human genomes and traits, with vast information already available from over half a million individuals in initiatives such as the UK Biobank. These resources are producing unparalleled insights into human biology, but the evolutionary processes that shaped human genomic variation—and continue to shape them in the future—can only be fully understood with direct data from the past. Cutting-edge ancient DNA technology now provides unprecedented possibilities to retrieve genome sequences from ancient populations, but few ancient whole genomes from Britain have been published. I propose to undertake reconstruction of fine-scale human evolution by extending available genomic data from the British population into a third dimension—the sequencing of 1,000 ancient genomes. This project aims to: 1\. Provide an enduring resource of more than 1,000 genomes from 4,500 years of the Britain's past, and information on sex, relatives, ancestry, and pathogen presence for additional ~2,000 samples. 2\. Trace ancestry changes through 4,500 years, untangling present-day population stratification hampering medical genetics studies. 3\. Characterise natural selection on single variants and polygenic traits through time, including in response to industrialization, epidemics, and environmental changes.