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MBE Advance Access originally published online on January 30, 2007
Molecular Biology and Evolution 2007 24(4):1012-1024; doi:10.1093/molbev/msm020
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© The Author 2007. 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 Articles

The Evolution of Seminal Ribonuclease: Pseudogene Reactivation or Multiple Gene Inactivation Events?

Slim O. Sassi*, Edward L. Braun{dagger} and Steven A. Benner*

* Foundation for Applied Molecular Evolution, Gainesville, Florida
{dagger} Department of Zoology, University of Florida, Gainesville

E-mail: ssassi{at}ffame.org.

Accepted for publication January 26, 2007.

Two approaches, one novel, are applied to analyze the divergent evolution of ruminant seminal ribonucleases (RNases), paralogs of the well-known pancreatic RNases of mammals. Here, the goal was to identify periods of divergence of seminal RNase under functional constraints, periods of divergence as a pseudogene, and periods of divergence driven by positive selection pressures. The classical approach involves the analysis of nonsynonymous to synonymous replacements ratios ({omega}) for the branches of the seminal RNase evolutionary tree. The novel approach coupled these analyses with the mapping of substitutions on the folded structure of the protein. These analyses suggest that seminal RNase diverged during much of its history after divergence from pancreatic RNase as a functioning protein, followed by homoplastic inactivations to create pseudogenes in multiple ruminant lineages. Further, they are consistent with adaptive evolution only in the most recent episode leading to the gene in modern oxen. These conclusions contrast sharply with the view, cited widely in the literature, that seminal RNase decayed after its formation by gene duplication into an inactive pseudogene, whose lesions were repaired in a reactivation event. Further, the 2 approaches, {omega} estimation and mapping of replacements on the protein structure, were compared by examining their utility for establishing the functional status of the seminal RNase genes in 2 deer species. Hog and roe deer share common lesions, which strongly suggests that the gene was inactive in their last common ancestor. In this specific example, the crystallographic approach made the correct implication more strongly than the {omega} approach. Studies of this type should contribute to an integrated framework of tools to assign functional and nonfunctional episodes to recently created gene duplicates and to understand more broadly how gene duplication leads to the emergence of proteins with novel functions.

Key Words: seminal ribonuclease • pseudogene • ruminant • gene duplication • novel function


Michele Vendruscolo, Associate Editor


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