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MBE Advance Access published online on October 25, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl162
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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 October 17, 2006

Research Article

Evaluation Of Whether Accelerated Protein Evolution In Chordates Has Occurred Before, After Or Simultaneously With Gene Duplication

Catrióna R. Johnston 1, Colm O'Dushlaine 2, David A. Fitzpatrick 1, Richard J. Edwards 1, and Denis C. Shields 1 *

1 UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
2 UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland; Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland

* To whom correspondence should be addressed.
Denis C. Shields, E-mail: denis.shields{at}ucd.ie


  Abstract

Gene duplication and loss are predicted to be at least of the order of the substitution rate, and are key contributors to the development of novel gene function and overall genome evolution. While it has been established that proteins evolve more rapidly after gene duplication, we were interested in testing to what extent this reflects causation or association. Therefore, we investigated the rate of evolution prior to gene duplication in chordates. Two patterns emerged; firstly, branches which are both preceded by a duplication and followed by a duplication display an elevated rate of amino acid replacement. This is reflected in the ratio of non-synonymous to synonymous substitution (mean Ka:Ks) of 0.44 compared to branches preceded by and followed by a speciation (mean Ka:Ks of 0.23). The observed patterns suggest that there can be simultaneous alteration in the selection pressures on both gene duplication and amino acid replacement, which may be consistent with co-occurring increases in positive selection, or alternatively with concurrent relaxation of purifying selection. The pattern is largely, but perhaps not completely, explained by the existence of certain families which have elevated rates of both gene duplication and amino acid replacement. Secondly, we observed accelerated amino acid replacement prior to duplication (mean Ka:Ks for post-speciation pre-duplication branches was 0.27). In some cases, this could reflect adaptive changes in protein function precipitating a gene duplication event. In conclusion, the circumstances surrounding the birth of new proteins may frequently involve simultaneous change in selection pressures on both gene copy-number and on amino acid replacement. More precise modelling of the relative importance of pre-duplication, post-duplication and simultaneous amino acid replacement will require larger and denser genomic datasets from multiple species, allowing simultaneous estimation of lineage-specific fluctuations in mutation rates and adaptive constraints.


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