Coevolution of gene expression among interacting proteins - PubMed (original) (raw)

Coevolution of gene expression among interacting proteins

Hunter B Fraser et al. Proc Natl Acad Sci U S A. 2004.

Abstract

Physically interacting proteins or parts of proteins are expected to evolve in a coordinated manner that preserves proper interactions. Such coevolution at the amino acid-sequence level is well documented and has been used to predict interacting proteins, domains, and amino acids. Interacting proteins are also often precisely coexpressed with one another, presumably to maintain proper stoichiometry among interacting components. Here, we show that the expression levels of physically interacting proteins coevolve. We estimate average expression levels of genes from four closely related fungi of the genus Saccharomyces using the codon adaptation index and show that expression levels of interacting proteins exhibit coordinated changes in these different species. We find that this coevolution of expression is a more powerful predictor of physical interaction than is coevolution of amino acid sequence. These results demonstrate that gene expression levels can coevolve, adding another dimension to the study of the coevolution of interacting proteins and underscoring the importance of maintaining coexpression of interacting proteins over evolutionary time. Our results also suggest that expression coevolution can be used for computational prediction of protein-protein interactions.

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Figures

Fig. 1.

Fig. 1.

Coevolution of sequence. (A) A histogram of the base 10 logarithms of variance in evolutionary rates for all 192,510 possible pairs of proteins in this study. The variance for each protein in a pair was calculated, and the lower of the two was used to represent the pair. The dashed line indicates the variance cutoff described in the main text. Note that evolutionary rates were normalized by the mean rate for each branch of the phylogenetic tree (see Materials and Methods). (B) A histogram of the correlation coefficients indicating the strength of amino acid sequence coevolution for 200 pairs of interacting proteins (solid line) and 26,596 pairs of noninteracting proteins (dashed line). The two distributions are significantly different from one another (KS test, P = 0.0069). Bin labels are the upper bound for each bin (e.g., the label 0.9 indicates 0.8 < r ≤ 0.9).

Fig. 2.

Fig. 2.

Coevolution of expression. (A) A histogram of the base 10 logarithms of variance in CAI for all 192,510 possible pairs of the 621 proteins in this study. The variance for each protein in a pair was calculated, and the lower of the two was used to represent the pair. The dashed line indicates the variance cutoff described in the main text. (B) A histogram of the correlation coefficients indicating the strength of CAI coevolution for 200 pairs of interacting proteins (solid line) and 11,581 pairs of noninteracting proteins (dashed line). The two distributions are significantly different from one another (KS test, P < 10-26). Bin labels are the upper bound for each bin (e.g., the label 0.9 indicates 0.8 < r ≤ 0.9).

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