Evolution of Proteins and Gene Expression Levels are Coupled in Drosophila and are Independently Associated with mRNA Abundance, Protein Length, and Number of Protein-Protein Interactions

Abstract

Organismic evolution requires that variation at distinct hierarchical levels and attributes be coherently integrated, often in the face of disparate environmental and genetic pressures. A central part of the evolutionary analysis of biological systems remains to decipher the causal connections between organism-wide (or genome-wide) attributes (e.g., mRNA abundance, protein length, codon bias, recombination rate, genomic position, mutation rate, etc) as well as their role-together with mutation, selection, and genetic drift-in shaping patterns of evolutionary variation in any of the attributes themselves. Here we combine genome-wide evolutionary analysis of protein and gene expression data to highlight fundamental relationships among genomic attributes and their associations with the evolution of both protein sequences and gene expression levels. Our results show that protein divergence is positively coupled with both gene expression polymorphism and divergence. We show moreover that although the number of protein-protein interactions in Drosophila is negatively associated with protein divergence as well as gene expression polymorphism and divergence, protein-protein interactions cannot account for the observed coupling between regulatory and structural evolution. Furthermore, we show that proteins with higher rates of amino acid substitutions tend to have larger sizes and tend to be expressed at lower mRNA abundances, whereas genes with higher levels of gene expression divergence and polymorphism tend to have shorter sizes and tend to be expressed at higher mRNA abundances. Finally, we show that protein length is negatively associated with both number of protein-protein interactions and mRNA abundance and that interacting proteins in Drosophila show similar amounts of divergence. We suggest that protein sequences and gene expression are subjected to similar evolutionary dynamics, possibly because of similarity in the fitness effect (i.e., strength of stabilizing selection) of disruptions in a gene's protein sequence or its mRNA expression. We conclude that, as more and better data accumulate, understanding the causal connections among biological traits and how they are integrated over time to constrain or promote structural and regulatory evolution may finally become possible.

RETRACTED: Why proteins evolve at different rates: The functional hypothesis versus the mistranslation‐induced protein misfolding hypothesis

“…Fraser and his colleagues have shown that protein evolutionary rate inversely correlates with the number of protein-protein interactions in yeast, i.e., the greater the number of interactions a protein has with other proteins, the slower is its likely evolution [12,14]. The negative correlation of the evolutionary rates with protein-protein interactions was also reported in C. elegans and Drosophila melanogaster [13,15]. Using curated sets of interacting protein crystal structures, Mintseris and Weng concluded that residues in the interfaces of obligate complexes tend to evolve at a relatively slower rate [16].…”

“…Protein evolutionary rates have been also reported to correlate with other genome variables ( Table 2) including expression level (or breadth) [10,15,[17][18][19][20][21][22][23] and a gene's propensity to be lost (computed based on the pattern of presence and absence of genes across multiple genomes) [24]. The functional hypothesis posits that each protein molecule by performing its function contributes a small amount to organism fitness, so mutations that reduce two proteins' functional output (e.g., catalytic rate) equally will have fitness effects weighted by the number of molecules of each protein in the cell, or their abundances, causing the more abundant protein to evolve slower.…”

Genomics of Adaptation to Multiple Concurrent Stresses: Insights from Comparative Transcriptomics of a Cichlid Fish from One of Earth’s Most Extreme Environments, the Hypersaline Soda Lake Magadi in Kenya, East Africa

“…However, the relationship between gene expression and protein sequence evolution remains largely debated. Some studies support decoupling of gene expression from sequence evolution as is suggested by our study, whereas several other studies have suggested a positive correlation between the two evolutionary processes in several species including bacteria, yeast (Kim and Yi 2007), Drosophila (Lemos et al 2005), ants (Hunt et al 2013), and mammals (Khaitovich et al 2005;Warnefors and Kaessmann 2013). Several factors have been suggested that may influence the evolution of protein sequences and gene expression including organismic attributes (e.g., protein protein interactions), mutation rates, and the strength of selection, which in turn determine if the two processes are coupled or decoupled.…”

Improvisation in evolution of genes and genomes: whose structure is it anyway?

“…The same patterns were observed in drosophila as well with a positive correlation between sequence divergence and expression [39,40]. The question is what drives retention of duplicates: sequence, function or regulation divergence.…”