Imputed transcriptional patterns in ancient genomes reveal molecular targets of selection

Abstract

The genetically regulated component of molecular traits can be imputed from ancient genomes, though low genotyping quality and genetic drift may impair accurate expression prediction and results interpretation. We developed tissue-specific gene expression and alternative splicing prediction models and applied them to over a thousand imputed ancient genomes spanning 10,000 years of Western Eurasian history. We revealed gene regulatory patterns diverging with time, space and genomic ancestry by fitting predicted transcriptional profiles onto multivariable models including these factors. By interpreting associations with time as recent natural selection we identify hits mediated by transcriptional changes. Finally, we fine-mapped these selection signals to tissue-specific transcriptional traits, explicitly accounting for prediction uncertainty. Among others, we elucidate the spatial patterns and the regulatory features promoting selection at LCT, FADS1, SLC22A5/P4HA2, ACAD10/OAS3 and find novel signals of selection at TBIMB6, SORD2P and AC012370.3.