Conserved non-coding sequences (CNSs) are genomic regions with exceptionally high similarity across divergent organisms, and therefore thought to be important for organism viability. CNSs are typically located by genes important for developmental regulation, and many show significant enhancer activity in brain5. Genes near CNSs with significantly accelerated rates of substitution in the human lineage (haCNSs)15 are particularly likely to show differential expression between regions of developing human neocortex3,5, suggesting transcriptional regulation by haCNSs may be important in human-specific neurodevelopment. Our results confirm and extend these findings (Table 1; Suppl. Table 9). Rostrally-enriched genes include significantly more haCNSs than caudally-enriched genes, consistent with the expanded frontal cortex in primates and the developmental role of haCNSs. We also find more haCNSs with areal expression patterns in postmitotic than germinal layers, even after accounting for the larger number of areal genes in postmitotic layers. Interestingly, nearly 25% of regional genes in IZ (11/45) were haCNSs. This result, which cannot be explained by over-representation of neural adhesion genes in IZ, suggests that IZ is of particular importance in areal cortical identity during human development53.
