Protein abundances are more conserved than mRNA abundances across diverse taxa

Abstract

Proteins play major roles in most biological processes; as a consequence, protein expression levels are highly regulated. While extensive post-transcriptional, translational and protein degradation control clearly influence protein concentration and functionality, it is often thought that protein abundances are primarily determined by the abundances of the corresponding mRNAs. Hence surprisingly, a recent study showed that abundances of orthologous nematode and fly proteins correlate better than their corresponding mRNA abundances. We tested if this phenomenon is general by collecting and testing matching large-scale protein and mRNA expression data sets from seven different species: two bacteria, yeast, nematode, fly, human, and rice. We find that steady-state abundances of proteins show significantly higher correlation across these diverse phylogenetic taxa than the abundances of their corresponding mRNAs (p=0.0008, paired Wilcoxon). These data support the presence of strong selective pressure to maintain protein abundances during evolution, even when mRNA abundances diverge.

Figure 1

(A) General scheme for collecting, organizing, and analyzing protein and mRNA expression datasets involved in the study. For each organism, expression datasets were either assembled or measured in-house, with protein and mRNA abundances estimated by mass spectrometry and single-channel microarrays, respectively. For the genes orthologous between each pair of organisms, we calculated the Spearman rank correlation between their corresponding protein levels and between their corresponding mRNA levels, as reported in (B). Blue and red represent protein-protein and mRNA-mRNA correlations, respectively, with darker boxes indicating those correlations with p-value < 0.01. White boxes down the diagonal are the protein-mRNA correlations within each species.

Figure 2

Protein abundances are better conserved across seven taxa than mRNA abundances. (A) Summary of the measured distributions of protein-protein correlations and mRNA-mRNA correlations as outlier box-plots indicating the median +/− 1 quartile, with whiskers indicating ±1.5 interquartile ranges. Individual observations with p-value < 0.01 are plotted as filled circles, and observations with p-value ≥ 0.01 as open circles. Additional statistical tests are in the online Supplement. (B) Correlations using only SAGE or RNAseq transcript abundance measurements for organisms for which those data were available. Protein abundance correlations are substantially larger than mRNA abundance correlations in all three available cases (n = 700, 774, and 2680 for yeast-nematode, yeast-fly, and fly-nematode comparisons, respectively).