Fig. 3: Signatures of species divergence and regulatory function of Ctr9 at translation genes.

A In a given row, each colored cell reports normalized divergence, the ratio of inter-subspecies divergence to within-subspecies polymorphism, at Ctr9 binding sites upstream of genes from the Gene Ontology term GO:0006412, translation, or all other genes of the genome, in a comparison between M. m. castaneus and the indicated population of a sister taxon. FRA, France; GER, Germany; IRA, Iran; AFG, Afghanistan; CZE, Czech Republic; KAZ, Kazakhstan. Cells are colored based on relative values. Values at the bottom report the results of an ANOVA testing for differences in normalized divergence between translation genes and controls (see Table 1 and Table S7). P-adj, screen p-value after correction for multiple testing; OR, odds ratio. B A portion of a Ctr9 binding footprint upstream of the translation gene Rps29 as an example of mouse subspecies variation. The x-axis reports position relative to the transcription start site. Each row reports the sequence of one mouse individual; at heterozygote loci, only the allele representing the alternate to the reference is shown, although our analysis methods accounted for both (see Methods). C Data are as in A, except that each value reports the number of sites divergent between M. m. castaneus and the indicated sister population in the region of interest, standardized by the length of the latter. D Data are as in A, except that each value reports the number of sites polymorphic within M. m. castaneus and/or the indicated sister population in the region of interest, standardized by the length of the latter. E Shown is an analysis of mouse subspecies divergence variation at Ctr9 binding sites, in genes stratified by membership in the translation gene cohort and allele-specific expression differences between CAST and 129 alleles in F1 hybrid stem cells (ASE; Marks et al. 2015; Table S5). For a given bar, the y-axis reports the percentage of genes in the indicated category containing variants in Ctr9 binding sites divergent between M. m. castaneus and one or more sister taxon (Table S8). *, Fisher’s exact test p = 0.02. F) Data and symbols are as in Fig. 1B except that each point reports a comparison of expression of one translation gene between Ctr9 knockdown and shRNA control mouse stem cells (Ruan et al. 2023), and red and black text inlays report the percentage of translation genes where expression was higher in the indicated genotype with and without filtering for significance, respectively.