MBE Advance Access published online on June 27, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg160
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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1 Department of Genetics, Smurfit Institute, University of Dublin, Trinity College, Dublin 2, Ireland
* To whom correspondence should be addressed. E-mail: faresm{at}tcd.ie.
To reach a functional and energetically stable conformation, many proteins need molecular helpers called chaperonins. Among the group II chaperonins, CCT proteins provide crucial machinery for the stabilization and proper folding of several proteins in the cytosol of eukaryotic cells through interactions that are subunit-specific and geometry-dependent. CCT proteins are made up of eight different subunits, all with similar sequences, positioned in a precise arrangement. Each subunit has been proposed to have a specialised function during the binding and folding of the CCT protein substrate. Here, we demonstrate that functional divergence occurred after several CCT duplication events due to the fixation of amino acid substitutions by positive selection. Sites critical for ATP and substrate binding were found to have undergone positive selection and functional divergence predominantly in subunits that bind tubulin but not actin. Furthermore, we show clear functional divergence between CCT subunits that bind the C-terminal domains of actin and tubulin and those that bind the N-terminal domains. Phylogenetic analyses could not resolve the deep relationships between most subunits, except for the groups Key Words:
CCT, Duplication, Positive selection, Functional divergence, Convergent evolution, Protein folding
© 2003 Society for Molecular Biology and Evolution
Original Articles
Positive Selection and Sub-Functionalisation of Duplicated CCT Chaperonin Subunits
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, suggesting several almost simultaneous ancient duplication events. Together the results support the idea that, in contrast to homo-oligomeric chaperonins such as GroEL, the high divergence level between CCT subunits is the result of positive selection after each duplication event to provide a specialised role for each CCT subunit in the different steps of protein folding.![]()
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