4/20/2023 0 Comments Chimpanzee buttHowever, when we analyzed KRAB-ZNF genes separately we observed a significant enrichment of genes of this family among differentially expressed genes in brain ( Table S1). This difference could have several explanations, including differences in array platform and gene representation. In contrast to these studies, we did not find TFs as a whole to be over-represented in the differentially expressed genes from any examined tissue ( Table S1). We were particularly interested in expression differences in brain, which was not investigated in previous studies of human and chimpanzee TFs ( 4). However, previous analyses of human and chimpanzee TF gene expression did not include a comparison of gene expression in brain.Īs previously noted ( 11), after our masking, most expression differences were seen in testis, whereas the four somatic tissues showed approximately the same number of differentially expressed genes ( Fig. These studies raise the intriguing hypothesis that differences in the expression and networking of specific TFs could be driving major changes between primate species. However, two recent studies have identified TF genes as enriched among genes with expression patterns that are under directional selection in humans ( 4, 10). Because of these predicted consequences, it is often assumed that TFs are evolutionarily stable, and indeed, TFs as a class are structurally well conserved ( 8). Whereas most cis-element mutations would be expected to have limited, localized effects, alterations in TF sequence and/or expression could alter the expression of hundreds of target genes in a coordinated fashion ( 8, 9). However, the molecular mechanisms underlying these well-documented species differences have not been elucidated.Īlthough some differences in human–chimpanzee gene expression may be due to cis-regulatory element divergence, transcription factors (TFs) represent another potential source of expression variability. The relative up-regulation of human genes in other functional categories, including neuroprotection and synaptic transport, has also been documented ( 7). These data, together with evidence of positive selection acting on the promoters of genes involved in energy metabolism during human evolution, indicate that increased energy production has been essential to the evolution of the human brain ( 6). Several studies have noted the up-regulation of genes and metabolites involved in oxidative metabolism and mitochondrial function in human brains compared with chimpanzee brains ( 2, 4, 5). Although the human brain is relatively energy-efficient per cell compared with brains of other species, this increased capacity imposes a significant metabolic and oxidative burden ( 2, 3). Humans differ from chimpanzees in a number of important anatomical and physiological respects, most strikingly in our enhanced cognitive abilities and a substantial increase in the relative size of the human brain ( 1). Our results suggest that concerted changes in a relatively small number of interacting TFs may coordinate major gene expression differences in human and chimpanzee brain. The differentially expressed TFs cluster within a robust regulatory network consisting of two distinct but interlinked modules, one strongly associated with energy metabolism functions, and the other with transcription, vesicular transport, and ubiquitination. We identified 90 TF genes with significantly different expression levels in human and chimpanzee brain among which the rapidly evolving KRAB-zinc finger genes are markedly over-represented. To assess this possibility, we analyzed microarray data from five tissues from humans and chimpanzees. While the mechanisms underlying these evolutionary changes have not been elucidated, altered activities of key transcription factors (TFs) could play a pivotal role. These differences correlate with metabolic changes, as evidenced by the relative up-regulation of energy-related genes and metabolites in human brain. Humans differ from other primates by marked differences in cognitive abilities and a significantly larger brain.
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