Post-translational buffering leads to convergent protein expression levels between primates

Differences in gene regulation between human and closely related species influence phenotypes that are distinctly human. While gene regulation is a multi-step process, the majority of research concerning divergence in gene regulation among primates has focused on transcription.  To gain a comprehensive view of gene regulation, we surveyed genome-wide ribosome occupancy, which reflects levels of protein translation, in lymphoblastoid cell lines derived from human, chimpanzee and rhesus macaque. We further integrated mRNA and protein level measurements collected from matching cell lines. We find that, in addition to transcriptional regulation, the major factor determining protein level divergence between human and closely related species is post-translational buffering. Inter-species divergence in transcription is generally propagated to the level of protein translation. In contrast, gene expression divergence is often attenuated post-translationally, potentially mediated through post-translational modifications.  Results from our analysis indicate that post-translational buffering is a conserved mechanism that led to relaxation of selective constraint on transcript levels in humans. Overall design: Using ribosome profiling assays, we measured levels of protein translation transcriptome-wide in lymphoblastoid cell lines derived from 4 HapMap Yoruba individuals, 5 chimpanzee individuals, and 5 rhesus macaque individuals. Note that the data uploaded for the 4 Yoruba individuals were generated by further sequencing the libraries generated as part of the Battle et al QTL mapping study (GSE61742). About 30~50% more data were generated for these individuals and the files uploaded here combined the new sequencing data with the old data from GSE61742 for each respective cell line.