Post-transcriptional mechanisms distinguish human and chimp forebrain progenitor cells

Abstract

The forebrain has expanded in size and complexity during hominoid evolution. The contribution of post-transcriptional control of gene expression to this process is unclear. Using in-depth proteomics in combination with bulk and single-cell RNA sequencing, we analyzed protein and RNA levels of almost 5,000 genes in human and chimpanzee forebrain neural progenitor cells. We found that species differences in protein expression level was often independent of RNA levels, and more frequent than transcriptomic differences. Low-abundant proteins were more likely to show species-specific expression levels, while proteins expressed at a high level appeared to have evolved under stricter constraints. Our study implicates a previously unappreciated broad and important role for post-transcriptional regulatory mechanisms in the evolution of the human forebrain.