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Abstract
BackgroundDifferences 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.ResultsTo 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.ConclusionsResults from our analysis indicate that post-translational buffering is a conserved mechanism that led to relaxation of selective constraint on transcript levels in humans.
Highlights
Differences in gene regulation between human and closely related species influence phenotypes that are distinctly human
After excluding sequencing reads that mapped to ribosomal RNA and other contaminating sources, we obtained a median of ~ 12 million uniquely mapped ribosome profiling sequencing reads per sample (Additional file 1: Table S1 and Additional file 2: Figure 1 S1a)
We found that divergence in translation efficiency is rare, which means that divergence between primate species at the transcript level often propagates to the level of protein translation
Summary
Differences in gene regulation between human and closely related species influence phenotypes that are distinctly human. Almost half of a century ago, King and Wilson postulated that gene regulation differences are the major factor driving phenotypic divergence between human and chimpanzee [1]. Differences in gene regulation have been reported to be the major factors determining phenotypic differences between closely related species [2, 3]. E.g. pelvic fin reduction in freshwater sticklebacks, demonstrate how changes in gene expression patterns could result in dramatic phenotypic divergence between closely related species [4]. Most studies investigating divergence in gene expression among primates focused on comparing expression levels of messenger RNA (mRNA) [5, 6, 11, 12]. Large-scale studies profiling the impact of genetic variation jointly on transcript and protein levels have begun to reveal clues on how protein
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