Contact Density Affects Protein Evolutionary Rate from Bacteria to Animals |
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Authors: | Tong Zhou D Allan Drummond Claus O Wilke |
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Institution: | (1) Center for Computational Biology and Bioinformatics, Section of Integrative Biology, University of Texas at Austin, Austin, TX 78731, USA;(2) FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA;(3) Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78731, USA |
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Abstract: | The density of contacts or the fraction of buried sites in a protein structure is thought to be related to a protein’s designability,
and genes encoding more designable proteins should evolve faster than other genes. Several recent studies have tested this
hypothesis but have found conflicting results. Here, we investigate how a gene’s evolutionary rate is affected by its protein’s
contact density, considering the four species Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. We find for all four species that contact density correlates positively with evolutionary rate, and that these correlations
do not seem to be confounded by gene expression level. The strength of this signal, however, varies widely among species.
We also study the effect of contact density on domain evolution in multidomain proteins and find that a domain’s contact density
influences the domain’s evolutionary rate. Within the same protein, a domain with higher contact density tends to evolve faster
than a domain with lower contact density. Our study provides evidence that contact density can increase evolutionary rates,
and that it acts similarly on the level of entire proteins and of individual protein domains.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | Designability Protein structure Evolutionary rate Protein evolution Domain Principal component regression |
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