Fig. 3.

Mitochondria-associated proteins are expressed in a more similar inter-regional pattern in dog and human brains compared with mouse. A, diagram of comparisons of regional and inter-regional expression patterns of orthologous proteins in four matched brain regions of dog, human, and mouse. B, the frequency distribution of Pearson correlations for each 1:1 ortholog (n = 2648) protein expression in four matched brain regions among dog (D), mouse (M), and human (H). The median correlation of human and dog proteome is higher than that between human and mouse proteome when all ortholog proteins are compared (0.66 versus 0.24). The box indicates orthologous proteins that are highly correlated between two of the three species (r > 0.67). C, protein abundance differences between two specific brain regions Stri and PFC in dog and human. Proteins are labeled as green if the magnitude of protein change in dog was <2-fold of that for human; red if the protein is changed between regions in opposite directions in dog and human; blue if the protein expression is consistently enriched in one region with a large difference of protein change magnitudes in two specific brain regions between dog and human (D/H or H/D > 2-fold), or the protein expression varies between regions only in human or in dog. D, bar plot of the percentage of protein numbers annotated in each of the color categories defined in (C) across all unique pairs of brain regions from the three species. The protein expression patterns in D-H were significantly different from that in M-H (Fisher’s exact test, ∗∗∗p < 0.001). Significantly, more orthologs are expressed similarly (green bar) in any two regions in dog and human brain than that in mouse and human brain. E, scatter plot shows GO and KEGG enrichment results of proteins with highly similar spatial expression patterns between dog and human brain (Pearson correlation coefficient D-H > 0.67; coefficient difference between D-H and M-H > 0.33, Fisher’s exact test, fc > 1.5, adjusted p < 0.05) or between mouse and human brain (D-H > 0.67; coefficient difference between M-H and D-H > 0.33). The proteins with highly similar spatial expression patterns in D-H (red) are enriched in mitochondria function, mitochondria-related disease, and myelin sheath, while the proteins with highly similar spatial expression patterns in M-H (blue) are not significantly enriched in any pathways. F, inter-regional expression patterns of mitochondria electron transport–related proteins similarly expressed in dog and human brain but different in mouse brain. The size of the circle indicates average expression level of all pathway-related proteins in each region. G, heatmap of z-scored intensities of representative proteins involved in mitochondria electron transport and myelin sheath with similar expression patterns in adult dog and human brain but different in mouse brain. KEGG, Kyoto Encyclopedia of Genes and Genomes; PFC, prefrontal cortex; Stri, striatum.