Fig. 1

Outline of the methodology. A Outline of a typical ASE pipeline. Hybrids are generated and RNA-seq is used to determine the relative expression of each allele. The ASE ratio is computed as the ratio of species-specific read counts between the two alleles. B The distribution of the variance in the ASE ratio for each gene in the GTEx data. Insets in orange show two genes at the extreme ends (EEF2 with low variance suggesting strong stabilizing selection and PDPR with high variance suggesting less constraint on gene expression). For visualization purposes, we removed the few genes with GTEx ASE variance greater than 1 in this panel only. C Schematic of incorporation of the interspecies ASE and population level ASE. ZNF331 has a wide range of ASE values, and the human-chimpanzee ASE is well within the population distribution whereas human-chimp ASE in RPS16 is on the edge of the population distribution indicating the greater potential for functional relevance. For both B and C, only GTEx brain samples were used as this provided clearer illustrative examples, though results are similar using all GTEx samples (Fig. 2A)