Evolutionary Rate Heterogeneity of Core and Attachment Proteins in Yeast Protein Complexes

Abstract

In general, proteins do not work alone; they form macromolecular complexes to play fundamental roles in diverse cellular functions. On the basis of their iterative clustering procedure and frequency of occurrence in the macromolecular complexes, the protein subunits have been categorized as core and attachment. Core protein subunits are the main functional elements, whereas attachment proteins act as modifiers or activators in protein complexes. In this article, using the current data set of yeast protein complexes, we found that core proteins are evolving at a faster rate than attachment proteins in spite of their functional importance. Interestingly, our investigation revealed that attachment proteins are present in a higher number of macromolecular complexes than core proteins. We also observed that the protein complex number (defined as the number of protein complexes in which a protein subunit belongs) has a stronger influence on gene/protein essentiality than multifunctionality. Finally, our results suggest that the observed differences in the rates of protein evolution between core and attachment proteins are due to differences in protein complex number and expression level. Moreover, we conclude that proteins which are present in higher numbers of macromolecular complexes enhance their overall expression level by increasing their transcription rate as well as translation rate, and thus the protein complex number imposes a strong selection pressure on the evolution of yeast proteome.

GECluster: a novel protein complex prediction method

“…Core proteins are those that are always present in all isoforms and execute the main functions, whereas attachment proteins are present only in some of the isoforms and act as modifiers of the complex's function. [ 22 ] Many researchers believe that core proteins evolve slower than attachment proteins, as core proteins are main functional elements,[ 23,24 ] which is in accordance with the proposal that functionally important genes should evolve slower than less important genes. However, a recent study by Chakraborty and Ghosh [ 22 ] revealed that core proteins evolve faster than attachment proteins in spite of their higher multi-functionality.…”

“…[ 22 ] Many researchers believe that core proteins evolve slower than attachment proteins, as core proteins are main functional elements,[ 23,24 ] which is in accordance with the proposal that functionally important genes should evolve slower than less important genes. However, a recent study by Chakraborty and Ghosh [ 22 ] revealed that core proteins evolve faster than attachment proteins in spite of their higher multi-functionality. The authors observed that attachment proteins play a role in a higher number of protein complexes than core proteins and, consequently, have an increased expression level, which is the main determining factor for the protein evolution rate.…”

“…Since previously performed protein complex evolution research is based on the protein complexes predicted by using low accuracy methods, it may not be completely correct. In this part of our study, the core and attachment protein dataset of [ 22 ] was used to analyse their evolutionary relationship. We count the core and attachment protein number in each network complex dataset.…”

Systematic Analyses and Prediction of Human Drug Side Effect Associated Proteins from the Perspective of Protein Evolution

“…2006; Park and Choi 2010; Panda et al. 2012; Chakraborty and Ghosh 2013; Wang et al. 2013a, 2013b; Begum and Ghosh 2014; Zhang and Yang 2015) those either have known correlations or we conjectured to have relation with protein evolutionary rates.…”

Link clustering explains non-central essential genes in protein interaction networks

“…Gene ages were 11 downloaded from the ProteinHistorian database [61]; specifically, we used protein families predicted 12 from the OrthoMCL and PANTHER databases, and ancestral history reconstructed by Dollo 13 parsimony. We used the pre-calculated set of dN/dS for yeast [62] and human [63], for which 14 evolutionary rates were computed with several species and the average was taken. 15…”