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. 2012 Sep 15;28(18):i389-i394.
doi: 10.1093/bioinformatics/bts396.

Uncovering the co-evolutionary network among prokaryotic genes

Ofir Cohen  1 , Haim Ashkenazy, David Burstein, Tal Pupko
Affiliations

Uncovering the co-evolutionary network among prokaryotic genes

Ofir Cohen et al. Bioinformatics. .

Abstract

Motivation: Correlated events of gains and losses enable inference of co-evolution relations. The reconstruction of the co-evolutionary interactions network in prokaryotic species may elucidate functional associations among genes.

Results: We developed a novel probabilistic methodology for the detection of co-evolutionary interactions between pairs of genes. Using this method we inferred the co-evolutionary network among 4593 Clusters of Orthologous Genes (COGs). The number of co-evolutionary interactions substantially differed among COGs. Over 40% were found to co-evolve with at least one partner. We partitioned the network of co-evolutionary relations into clusters and uncovered multiple modular assemblies of genes with clearly defined functions. Finally, we measured the extent to which co-evolutionary relations coincide with other cellular relations such as genomic proximity, gene fusion propensity, co-expression, protein-protein interactions and metabolic connections. Our results show that co-evolutionary relations only partially overlap with these other types of networks. Our results suggest that the inferred co-evolutionary network in prokaryotes is highly informative towards revealing functional relations among genes, often showing signals that cannot be extracted from other network types.

Availability and implementation: Available under GPL license as open source.

Contact: talp@post.tau.ac.il.

Supplementary information: Supplementary data are available at Bioinformatics online.

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Figures

Fig. 1.
Fig. 1.
Methodology outline. Given an input of phyletic pattern and a phylogenetic tree, we detect correlated evolutionary histories and use simulations to infer significant co-evolving genes
Fig. 2.
Fig. 2.
Degree distribution of the co-evolutionary network on a log–log scale. All 4,593 COGs are ranked according to their degree. In total, 1,940 COGs have at least one connection.
Fig. 3.
Fig. 3.
The flagellum-related cluster. This cluster contains 30 highly connected COGs (the nodes in the figure), all flagellar-related and is the biggest cluster of co-evolutionary genes
Fig. 4.
Fig. 4.
Functional modules of co-evolving genes that include an uncharacterized member. (A) ‘Mu-like prophage’ cluster (B) ‘Type IV secretory pathway’ cluster. Yellow nodes correspond to COGs that are uncharacterized
See this image and copyright information in PMC

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