Evolution of protein-coding genes across tissues and biological functions. (A) Analysis pipeline for the extraction of ωGC12, a corrected and normalized measurement of the evolution of protein-coding genes that behaves like a Z-score and takes into account the GC content of codons. (B) Hierarchical clustering, based on ωGC12, across all protein-coding genes (1:1 orthologs in hominins with medium coverage) (Supplemental Table S1). (C) Gene Ontology (GO) enrichments for the red and blue clusters in B (for all GO terms, see Supplemental Table S2). Horizontal lines indicate 95% confidence intervals. (D) Funnel plot summarizing the evolution of protein-coding genes specifically expressed in different tissues of the human body (Supplemental Table S3). Horizontal and vertical axes indicate, respectively, the effect size and the statistical significance. Circle size indicates the number of proteins in the set. The dashed horizontal line indicates the threshold for significance after Bonferroni correction. Stars indicate the set of genes for which statistical significance was achieved in multiple comparisons after correction, with a bootstrap taking GC12 content and coding sequence length into account. (HS) Homo sapiens; (6-EPO ancestor) the reconstructed ancestral genome of primates based on alignments of Homo sapiens, chimpanzee, gorilla, orangutan, rhesus macaque, and marmoset genomes.
