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Published online on February 14, 2007, 10.1073/pnas.0610797104
PNAS | February 20, 2007 | vol. 104 | no. 8 | 2779-2784


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BIOLOGICAL SCIENCES / EVOLUTION
Tissue-driven hypothesis of genomic evolution and sequence-expression correlations

Xun Gu*,{dagger},{ddagger}, and Zhixi Su*

*School of Life Sciences, Institutes of Biomedical Sciences, Center for Evolutionary Biology, Fudan University, Shanghai 200433, China; and {dagger}Department of Genetics, Development, and Cell Biology, Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, IA 50011

Communicated by Jiazhen Tan, Fudan University, Shanghai, China, December 18, 2006 (received for review September 30, 2006)

To maintain normal physiological functions, different tissues may have different developmental constraints on expressed genes. Consequently, the evolutionary tolerance for genomic evolution varies among tissues. Here, we formulate this argument as a "tissue-driven hypothesis" based on the stabilizing selection model. Moreover, several predicted genomic correlations are tested by the human–mouse microarray data. Our results are as follows. First, between the human and mouse, we have elaborated the among-tissue covariation between tissue expression distance (Eti) and tissue sequence distance (Dti). This highly significant Eti – Dti correlation emerges when the expression divergence and protein sequence divergence are under the same tissue constraints. Second, the tissue-driven hypothesis further explains the observed significant correlation between the tissue expression distance (between the human and mouse) and the duplicate tissue distance (Tdup) between human (or mouse) paralogous genes. In other words, between-duplicate and interspecies expression divergences covary among tissues. Third, for genes with the same expression broadness, we found that genes expressed in more stringent tissues (e.g., neurorelated) generally tend to evolve more slowly than those in more relaxed tissues (e.g., hormone-related). We conclude that tissue factors should be considered as an important component in shaping the pattern of genomic evolution and correlations.

expression divergence | tissue expression | mammalian genomics | gene duplications

Author contributions: X.G. designed research; X.G. and Z.S. performed research; X.G. contributed new reagents/analytic tools; X.G. and Z.S. analyzed data; and X.G. and Z.S. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0610797104/DC1.

{ddagger}To whom correspondence should be addressed at: 536 Science II Hall, Iowa State University, Ames, IA 50011. E-mail: xgu{at}iastate.edu

© 2007 by The National Academy of Sciences of the USA


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