Testing for ancient selection using cross-population allele

A powerful way to detect selection in a population is by modeling local allele frequency changes in a 7 particular region of the genome under scenarios of selection and neutrality, and finding which model is 8 most compatible with the data. Chen et al. [1] developed a composite likelihood method called XP-CLR 9 that uses an outgroup population to detect departures from neutrality which could be compatible with 10 hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent 11 selection and may miss selective events that happened a long time ago. To overcome this, we developed 12 an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. 13 Our method called 3P-CLR outperforms XP-CLR when testing for selection that occurred before two 14 populations split from each other, and can distinguish between those events and events that occurred 15 specifically in each of the populations after the split. We applied our new test to population genomic 16 data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of 17 Africans and Eurasians, but after their split from Neanderthals, and that could have presumably led to 18 the fixation of modern-human-specific phenotypes. We also searched for sweep events that occurred in 19 East Asians, Europeans and the ancestors of both populations, after their split from Africans. 20