Comparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human

Abstract

Epigenetic information regulates gene expression and development. However, our understanding of the evolution of epigenetic regulation on brain development in primates is limited. Here, we compared chromatin accessibility landscapes and transcriptomes during fetal prefrontal cortex (PFC) development between rhesus macaques and humans. A total of 304,761 divergent DNase I-hypersensitive sites (DHSs) are identified between rhesus macaques and humans, although many of these sites share conserved DNA sequences. Interestingly, most of the cis-elements linked to orthologous genes with dynamic expression are divergent DHSs. Orthologous genes expressed at earlier stages tend to have conserved cis-elements, whereas orthologous genes specifically expressed at later stages seldom have conserved cis-elements. These genes are enriched in synapse organization, learning and memory. Notably, DHSs in the PFC at early stages are linked to human educational attainment and cognitive performance. Collectively, the comparison of the chromatin epigenetic landscape between rhesus macaques and humans suggests a potential role for regulatory elements in the evolution of differences in cognitive ability between non-human primates and humans.

Human gene regulatory evolution is driven by the divergence of regulatory element function in bothcisandtrans

“…We first determined accessibility peaks using the sequence reads obtained from the input DNA libraries, as previously described. 37 Previous studies have investigated regions of differential chromatin accessibility in primate LCLs and other tissues, [42][43][44][45] and consistent with these results, most chromatin accessibility peaks identified between the human and macaque genomes (59,144, 67%) is speciesspecific, while 29,531 (33%) peaks had shared accessibility between species (Figure 1C). As expected, we find that divergent accessibility peaks are distally located and enriched for cell-type relevant functions (Figure 1D, S1C-G).…”

Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to the human brain evolution

“…Variations in transcriptional regulatory systems may drive the acquisition of new traits 24,25,43 and the analysis of interspecies differences in chromatin accessibility helps reveal mechanisms orchestrating the alteration of gene expression in evolution 13,[44][45][46][47] . We adopted an ATAC-seqbased approach to best account for the evolutionary changes in cis-regulatory element (CRE) activity.…”

Keeping the balance: Trade-offs between human brain evolution, autism, and schizophrenia

“…5 Summary-Perspectives and future avenues for research One of the essential questions in neurobiology is how the genome changed to allow the increased intellectual abilities of humans compared to NHP. The discovery of the human-specific regulome of the nervous system is likely to provide important piece of information to solve this question (Yao et al, 2022). Addressing it will also likely help us understand the genetic bases of diseases that affect human specific features of mind.…”

“…Furthermore, regions that have undergone a selective sweep in humans after divergence from Neanderthals are enriched in enhancers ( Peyregne et al, 2017 ). Interestingly, active chromatin regions in humans, especially those elements which are active earlier in fetal development, have been linked to cognitive ability ( Yao et al, 2022 ).…”