Ancestral Spectrum Analysis With Population-Specific Variants

With the advance of sequencing technology, an increasing number of populations have been sequenced to study the histories of worldwide populations, including their divergence, admixtures, migration, and effective sizes. The variants detected in sequencing studies are largely rare and mostly population specific. Population-specific variants are often recent mutations and are informative for revealing substructures and admixtures in populations; however, computational methods and tools to analyze them are still lacking. In this work, we propose using reference populations and single nucleotide polymorphisms (SNPs) specific to the reference populations. Ancestral information, the best linear unbiased estimator (BLUE) of the ancestral proportion, is proposed, which can be used to infer ancestral proportions in recently admixed target populations and measure the extent to which reference populations serve as good proxies for the admixing sources. Based on the same panel of SNPs, the ancestral information is comparable across samples from different studies and is not affected by genetic outliers, related samples, or the sample sizes of the admixed target populations. In addition, ancestral spectrum is useful for detecting genetic outliers or exploring co-ancestry between study samples and the reference populations. The methods are implemented in a program, Ancestral Spectrum Analyzer (ASA), and are applied in analyzing high-coverage sequencing data from the 1000 Genomes Project and the Human Genome Diversity Project (HGDP). In the analyses of American populations from the 1000 Genomes Project, we demonstrate that recent admixtures can be dissected from ancient admixtures by comparing ancestral spectra with and without indigenous Americans being included in the reference populations.