Extended Data Fig. 5: Functional annotation of tissue-specific genes and their sequence conservation in mammals.

(a) Significant Gene Ontology (GO) terms for genes with tissue-specific expression, based on the one-sided Fisher’s exact test using ClusterProfiler v3.0.4. FDR is obtained after the Benjamini-Hochberg correction for the raw P value. (b) Significant GO terms for genes with tissue-specific hypomethylated promoters (P < 0.05). (c) Significant GO terms for genes with brain-specific spliced introns (Benjamini-Hochberg corrected P (FDR) < 0.05 after correction). (d) dN/dS ratio (between cattle and humans) of orthologous genes with tissue-specific expression across tissues. The red dash line indicates median value of 0.154. (e) PhastCons scores of regions with tissue-specific hypomethylation across tissues. PhastCons scores were obtained from UCSC website and calculated on the basis of DNA sequences of 46 placental mammals. The red dash line indicates the median value of 0.1. (f) The Pearson’s correlation (r = −0.68, the two-sided Student’s t-test: P = 0.0036) between PhastCons scores of tissue-specific DNA methylation regions and dN/dS ratios of tissue-specific expressed genes across 16 common tissues. (f) has the same color key as (d).