Figure 2. Genes associated with BW show differential effects across species.

(A) Grid plot showing BW-associated genes that are also significantly differentially expressed in humans relative to chimpanzees and macaques (p_Bonferroni < 0.05), across 16 brain regions (11 neocortical areas). These are BW-associated genes that were previously defined⁴² as having higher or lower expression compared with the two species collectively, and reanalyzed to assess stepwise interspecies effects that reflect the absolute differences in brain size between species (i.e., up-regulated implies gene expression humans > chimpanzees > macaques, while downregulated implies gene expression humans < chimpanzees < macaques). Triangles represent directions of effects and colors denote the respective BW gene set. Genes that are highlighted show congruent directional effects in respective BW sets (i.e., BW+ and upregulated in humans, and vice versa).

(B) Brain plots of differences in counts of number of BW+ or BW− genes that were defined to be significantly differentially expressed in humans relative to macaques each of three developmental epochs—a positive regional difference (blue) indicates that BW+ genes tend to be upregulated in humans in that region in a given developmental epoch, while a negative difference (red) indicates that BW− genes tend to be upregulated. The same 16 regions from (A) are shown anatomically, based on manual assignment using a common human atlas.⁴⁴

(C) Differential expression of BW+ versus BW− genes across individual cell types, using cell-specific RNA sequencing data in fetal and adult samples from macaques (left) and humans (right). BW− relative expression (red) indicates that BW− genes are more highly expressed in that cell type compared with BW+, whereas BW+ relative expression (blue) indicates the opposite effect. Black outlines denote significant effects (p_Bonferroni < 0.05). Circles are scaled according to Bonferroni-corrected p values. Black rectangles denote human-specific effects relative to macaques. V1C, primary visual cortex; M1C, primary motor cortex; S1C, primary somatosensory cortex; A1C, primary auditory cortex; ITC, inferior temporal cortex; IPC, inferior parietal cortex; STC, superior temporal cortex; OFC, orbitofrontal cortex; VFC, ventrolateral frontal cortex; DFC, dorsolateral frontal cortex; MFC, medial frontal cortex; STR, striatum; MD, medial dorsal thalamus; AMY, amygdala; HIP, hippocampus; CBC, cerebellar cortex. Astro, astrocytes; Endo, endothelial cells; ExN, excitatory neurons; InN, inhibitory neurons; NasN, nascent neurons; Oligo, oligodendrocytes; OPC, oligodendrocyte precursor cells.