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Open Access Research article

Functional divergence of gene duplicates – a domain-centric view

Mugdha Khaladkar1 and Sridhar Hannenhalli2*

Author Affiliations

1 Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104, USA

2 University of Maryland, 3104G Biomolecular Sciences Building (#296), College Park, MD, USA

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BMC Evolutionary Biology 2012, 12:126  doi:10.1186/1471-2148-12-126

Published: 27 July 2012



Gene duplicates have been shown to evolve at different rates. Here we further investigate the mechanism and functional underpinning of this phenomenon by assessing asymmetric evolution specifically within functional domains of gene duplicates.


Based on duplicate genes in five teleost fishes resulting from a whole genome duplication event, we first show that a Fisher Exact test based approach to detect asymmetry is more sensitive than the previously used Likelihood Ratio test. Using our Fisher Exact test, we found that the evolutionary rate asymmetry in the overall protein is largely explained by the asymmetric evolution within specific protein domains. Moreover, among cases of asymmetrically evolving domains, for the gene copy containing a fast evolving domain, the non-synonymous substitutions often cluster within the fast evolving domain. We found that rare substitutions were preferred within asymmetrically evolving domains suggestive of functional divergence. While overall ~32 % of the domains tested were found to be evolving asymmetrically, certain protein domains such as the Tyrosine and Ser/Thr Kinase domains had a much greater prevalence of asymmetric evolution. Finally, based on the spatial expression of Zebra fish duplicate proteins during development, we found that protein pairs containing asymmetrically evolving domains had a greater divergence in gene expression as compared to the duplicate proteins that did not exhibit asymmetric evolution.


Taken together, our results suggest that the previously observed asymmetry in the overall duplicate protein evolution is largely due to divergence of specific domains of the protein, and coincides with divergence in spatial expression domains.

Gene duplication; Whole genome duplication; Computational biology; Evolution