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MBE Advance Access originally published online on December 20, 2005
Molecular Biology and Evolution 2006 23(3):675-682; doi:10.1093/molbev/msj081
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© The Author 2005. 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

Research Article

Alternatively and Constitutively Spliced Exons Are Subject to Different Evolutionary Forces

Feng-Chi Chen*, Sheng-Shun Wang{dagger}, Chuang-Jong Chen*, Wen-Hsiung Li*,{ddagger} and Trees-Juen Chuang*

* Genomics Research Center and {dagger} Institute of Information Science, Academia Sinica, Taipei, Taiwan; and {ddagger} Department of Ecology and Evolution, University of Chicago

E-mail: trees{at}gate.sinica.edu.tw.

There has been a controversy on whether alternatively spliced exons (ASEs) evolve faster than constitutively spliced exons (CSEs). Although it has been noted that ASEs are subject to weaker selective constraints than CSEs, so they evolve faster, there have also been studies that indicated slower evolution in ASEs than in CSEs. In this study, we retrieve more than 5,000 human-mouse orthologous exons and calculate the synonymous (KS) and nonsynonymous (KA) substitution rates in these exons. Our results show that ASEs have higher KA values and higher KA/KS ratios than CSEs, indicating faster amino acid–level evolution in ASEs. The faster evolution may be in part due to weaker selective constraints. It is also possible that the faster rate is in part due to faster functional evolution in ASEs. On the other hand, the majority of ASEs have lower KS values than CSEs. With reference to the substitution rate in introns, we show that the KS values in ASEs are close to the neutral substitution rate, whereas the synonymous substitution rate in CSEs has likely been accelerated. The elevated synonymous rate in CSEs is not related to CpG dinucleotides or low-complexity regions of protein but may be weakly related to codon usage bias. The overall trends of higher KA and lower KS in ASEs than in CSEs are also observed in human-rat and mouse-rat comparisons. Therefore, our observations hold for mammals of different molecular clocks.

Key Words: selective constraint • alternatively spliced exons • constitutively spliced exons • synonymous/nonsynonymous substitution • comparative genomics


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