Whole-genome from Chilean Indigenous populations
South America's rich cultural diversity has been contrasted with its relatively low genetic diversity, associated with the founding bottleneck and with decimations post European contact. Nevertheless, this picture was mostly built on data from uniparental markers and genome-wide SNP arrays designed with ascertainment biases due to large geographic gaps in sampling. Here we sequence 20 high-coverage genomes from populations in Central-Southern Chile, with limited European admixture, and analyze them alongside high-quality ancient and modern genomes. Compared with SNP array data, the whole-genome sequencing data from the Southern Cone revealed higher values of nucleotide diversity, comparable to Eurasian populations. The elevated number of genetic variants within populations, possibly explained by large and sustained population sizes, challenges previous assumptions of South American populations being small and isolated. Additionally, we infer a minor pulse of gene flow from an ancient genetic source. Whole-genome sequencing enables finer demographic reconstructions in the Americas and facilitates connecting present-day indigenous ancestries with the dynamics of first inhabitants.