Comparison of protein and mRNA expression evolution in humans and chimpanzees

Abstract

Even though mRNA expression levels are commonly used as a proxy for estimating functional differences that occur at the protein level, the relation between mRNA and protein expression is not well established. Further, no study to date has tested whether the evolutionary differences in mRNA expression observed between species reflect those observed in protein expression. Since a large proportion of mRNA expression differences observed between mammalian species appears to have no functional consequences for the phenotype, it is conceivable that many or most mRNA expression differences are not reflected at the protein level. If this is true, then differences in protein expression may largely reflect functional adaptations observed in species phenotypes. In this paper, we present the first direct comparison of mRNA and protein expression differences seen between humans and chimpanzees. We reproducibly find a significant positive correlation between mRNA expression and protein expression differences. This correlation is comparable in magnitude to that found between mRNA and protein expression changes at different developmental stages or in different physiological conditions within one species. Noticeably, this correlation is mainly due to genes with large expression differences between species. Our study opens the door to a new level of understanding of regulatory evolution and poses many new questions that remain to be answered.

Figure 1

Schematic representation of gene expression variation within and between species on mRNA (A) and protein (B) levels. The trees are inferred from the mean of the squared difference of expression intensities for 98 genes detected on both mRNA and protein levels. Each pool represents an average expression in two chimpanzee (c) or two human (h) individuals. Additionally, protein measurements are based on two independent experimental replicates.

Figure 2

Comparison of protein and mRNA expression differences between humans and chimpanzees. Comparisons are shown for 98 genes, detected on both mRNA and protein levels (A), and for 33 genes showing significant differences in mRNA (⧫) or protein (+) expression between the species (B). Six genes significantly different on both mRNA and protein expression levels are shown using overlapping labels. The names and the functional annotation of the 33 genes are included in table S5. Expression differences are shown using a base-two logarithmic scale. The dotted line represents an ideal regression line (α = 0, β = 1).