<p>A major challenge in human evolutionary biology is to pinpoint the genetic differences that underlie phenotypic changes in the human lineage, such as increased neuron number and a prolonged period of neuronal maturation. Here, we used human-chimpanzee tetraploid cells to distinguish changes in gene expression due to cis-acting sequence variants that change local gene regulation, from trans expression changes due to species differences in the cellular environment, in neural progenitor cells and excitatory neurons using RNA-seq and ATAC-seq. Using a CRISPR inhibition screen with scRNA-seq, transcription factor motif analyses with CUT&#x26;Tag, and downstream single-locus studies with RNA-seq, we further characterized cis-acting gene regulatory differences, including changes to <a href="https://www.ncbi.nlm.nih.gov/gene/2353">FOS</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/23043">TNIK</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/2355">FOSL2</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/4150">MAZ</a>, that influence neurogenesis and neuronal maturation. This study identifies specific genomic changes that may contribute to human neural specializations and provides a general framework for understanding genetic differences that underlie human traits.</p>

Uncovering Gene Regulatory Differences between Human and Chimpanzee Neural Cells

Human-chimpanzee tetraploid system defines mechanisms of species-specific neural gene regulation

FOS binding sites are a hub for the evolution of activity-dependent gene regulatory programs in human neurons