@article {539541,
	title = {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},
	journal = {Mol Biol Evol},
	volume = {22},
	number = {5},
	year = {2005},
	note = {<p>Lemos, BernardoBettencourt, Brian RMeiklejohn, Colin DHartl, Daniel LengComparative StudyResearch Support, N.I.H., ExtramuralResearch Support, U.S. Gov{\textquoteright}t, P.H.S.2005/03/05 09:00Mol Biol Evol. 2005 May;22(5):1345-54. Epub 2005 Mar 2.</p>},
	month = {May},
	pages = {1345-54},
	abstract = {<p>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{\textquoteright}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.</p>},
	keywords = {*Evolution, Molecular, *Gene Expression, *Genetic Variation, Animals, Drosophila Proteins/*genetics/metabolism, Drosophila/*genetics/metabolism, RNA, Messenger/*genetics/metabolism, Selection, Genetic},
	isbn = {0737-4038 (Print)0737-4038 (Linking)},
	author = {Lemos, B. and Bettencourt, B. R. and Meiklejohn, C. D. and Hartl, D. L.}
}
