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MBE Advance Access published online on August 3, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl076
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted July 31, 2006

Research Article

Impacts of Gene Essentiality, Expression Pattern, and Gene Compactness on the Evolutionary Rate of Mammalian Proteins

Ben-Yang Liao 1, Nicole M. Scott 2, and Jianzhi Zhang 1 *

1 Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA
2 Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA

* To whom correspondence should be addressed.
Jianzhi Zhang, E-mail: jianzhi{at}umich.edu


  Abstract

Understanding the determinants of the rate of protein sequence evolution is of fundamental importance in evolutionary biology. Many recent studies have focused on the yeast because of the availability of many genome-wide expressional and functional data. Yeast studies revealed a predominant role of gene expression level and a minor role of gene essentiality in determining the rate of protein sequence evolution. Whether these rules apply to complex organisms such as mammals is unclear. Here we assemble a list of 1,138 essential and 2,341 nonessential mouse genes based on targeted gene deletion experiments and report a significant impact of gene essentiality on the rate of mammalian protein evolution. Gene expression level has virtually no effect, although tissue-specificity in expression pattern has a strong influence. Unexpectedly, gene compactness, measured by average intron size and UTR (untranslated region) length, has the greatest influence. Hence, the relative importance of the various factors in determining the rate of mammalian protein evolution is gene compactness > gene essentiality {approx} tissue-specificity > expression level. Our results suggest a considerable variation in rate determinants between unicellular organisms such as the yeast and multicellular organisms such as mammals.

Keywords: evolutionary rate; gene essentiality; tissue-specificity; expression level; gene compactness; mammals.
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