Human brain evolution: Emerging roles for regulatory DNA and RNA

Abstract

Humans diverge from other primates in numerous ways, including their neuroanatomy and cognitive capacities. Human-specific features are particularly prominent in the cerebral cortex, which has undergone an expansion in size and acquired unique cellular composition and circuitry. Human-specific gene expression is postulated to explain neocortical anatomical differences across evolution. In particular, noncoding regulatory loci are strongly linked to human traits, including progenitor proliferation and cortical size. In this review, we highlight emerging noncoding elements implicated in human cortical evolution, including roles for regulatory DNA and RNA. Further, we discuss the association of human-specific genetic changes with neurodevelopmental diseases.

Figure 1.. Evolutionary development of the human cortex

A. Graph showing a phylogenetic tree indicating the brain morphology of chimpanzee and rodents compared to humans. Primate stem has been highlighted. B. Cartoon representing comparisons of rodent and primate neocortical development. Progenitors are designated by their locations in the cortex. Apical radial glia (aRGs) which localize to the ventricular zone (VZ) can undergo symmetric and asymmetric divisions to self-renew or produce neurons directly or indirectly by producing intermediate progenitors (IPC) in the subventricular zone (SVZ). Newborn neurons will migrate through the intermediate zone (IZ) and arrive to the cortical plate (CP) with first born neurons located deeper and late born neurons located superficially. In the developing primate brain, SVZ expansion leads to a new germinal zone, the outer subventricular zone (OSVZ), which includes proliferative IPCs and basal radial glia cells (bRGs). The expansion of basal progenitors in turn, leads to more upper layer (mainly layer II/III) neurons in the primate neocortex. C. Comparisons of notable cellular differences between human and non-human primate cortical development.

Figure 2.. Non-coding regulatory elements in human brain evolution

Cartoon showing genomic modifications during human brain evolution. Representation of epigenetic changes, non-coding DNA and RNA alterations which have been implicated in human brain evolution, including the HARs, genomic methylation, and diversity of non-coding RNAs.