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Open Access Debate

Evolutionary rate depends on number of protein-protein interactions independently of gene expression level

Hunter B Fraser1* and Aaron E Hirsh2

Author Affiliations

1 Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA

2 Department of Biological Sciences, Stanford University, Stanford, CA, 94305, USA

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BMC Evolutionary Biology 2004, 4:13  doi:10.1186/1471-2148-4-13

Published: 27 May 2004



Whether or not a protein's number of physical interactions with other proteins plays a role in determining its rate of evolution has been a contentious issue. A recent analysis suggested that the observed correlation between number of interactions and evolutionary rate may be due to experimental biases in high-throughput protein interaction data sets.


The number of interactions per protein, as measured by some protein interaction data sets, shows no correlation with evolutionary rate. Other data sets, however, do reveal a relationship. Furthermore, even when experimental biases of these data sets are taken into account, a real correlation between number of interactions and evolutionary rate appears to exist.


A strong and significant correlation between a protein's number of interactions and evolutionary rate is apparent for interaction data from some studies. The extremely low agreement between different protein interaction data sets indicates that interaction data are still of low coverage and/or quality. These limitations may explain why some data sets reveal no correlation with evolutionary rates.