Large and fast excitatory transcriptomic neuron types in human cortex preferentially express genes of intelligence and HARs.

Abstract

Abstract Human intelligence is a highly heritable trait, and GWAS have yielded numerous associated genes. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether genes associated with human cognition and HAR genes are similarly expressed in adult human cortical neurons and brain areas of cognition, and how their expression relates to neuronal function and structure. We find that these gene sets are preferentially expressed in L3 excitatory neurons in middle temporal gyrus (MTG). Furthermore, neurons with higher expression had larger dendrites and faster action potential kinetics, properties previously linked to intelligence. Finally, we identify a subset of genes associated with dendritic length, with predominantly synaptic functions and high abundance of HARs. Our results indicate that mechanisms underlying human brain evolution and interindividual differences in intelligence might share genetic origin and manifest in specific neuronal types.