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

Abstract

Background: 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. Results: 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 messenger RNA 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. Conclusions: 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.