Primate transcript and protein expression levels evolve under compensatory selection pressures - PubMed (original) (raw)

Primate transcript and protein expression levels evolve under compensatory selection pressures

Zia Khan et al. Science. 2013.

Abstract

Changes in gene regulation have likely played an important role in the evolution of primates. Differences in messenger RNA (mRNA) expression levels across primates have often been documented; however, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are probably more important in determining phenotypic differences. We used high-resolution, quantitative mass spectrometry to collect protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines and compared them to transcript expression data from the same samples. We found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest that protein expression levels evolve under stronger evolutionary constraint than mRNA levels.

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Conflict of interest statement

Conflict of interest statement: JKP is on the scientific advisory boards for 23andMe and DNANexus with stock options.

Figures

Fig. 1

Fig. 1

Protein expression levels evolve under greater evolutionary constraint than mRNA expression levels. (a) A Venn diagram of the numbers of mRNAs (red) and proteins (blue) classified as differentially expressed (DE). (b) Mean effect size of the inter-species difference in expression for genes classified as DE as mRNA-only, protein-only, or both. Each point corresponds to a single DE gene. (c) Scatterplot of median mRNA and protein divergence of genes where estimates of mRNA and protein divergence between human and chimpanzee differed significantly (FDR = 1%). (d) 95% confidence intervals around estimates of mean mRNA and protein divergence of genes in (c).

Fig. 2

Fig. 2

Properties of genes whose protein and mRNA expression levels are inferred to have evolved under stabilizing selection. Error bars represent the 95% confidence intervals around the mean. Data are shown for the top 300 genes with the least varied mRNA (red) or protein (blue) expression levels between and within species. Gray bars correspond to all other genes.

Fig. 3

Fig. 3

Examples of genes whose mRNA and protein expression levels are consistent with different evolutionary scenarios. (a) A gene whose mRNA and protein expression levels are consistent with a lineage-specific change in posttranscriptional regulation. (b) A gene whose inter-species mRNA levels are consistent with buffering or compensation at the protein expression level. In both cases, RNA-seq coverage is standardized to per million mapped reads and averaged across all 5 individuals. Protein measurements are plotted at the starting genomic position of the peptides. The plots on the right are of mRNA and protein expression levels from all individuals, normalized relative to the internal standard cell line.

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