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Open Access Highly Accessed Research article

Transcriptomic and phylogenetic analysis of a bacterial cell cycle reveals strong associations between gene co-expression and evolution

Gang Fang12, Karla D Passalacqua3, Jason Hocking4, Paula Montero Llopis1, Mark Gerstein25, Nicholas H Bergman3 and Christine Jacobs-Wagner146*

Author Affiliations

1 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA

2 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA

3 School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA

4 Howard Hughes Medical Institute, Yale University, New Haven, CT 06511, USA

5 Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA

6 Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06511, USA

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BMC Genomics 2013, 14:450  doi:10.1186/1471-2164-14-450

Published: 5 July 2013

Abstract

Background

The genetic network involved in the bacterial cell cycle is poorly understood even though it underpins the remarkable ability of bacteria to proliferate. How such network evolves is even less clear. The major aims of this work were to identify and examine the genes and pathways that are differentially expressed during the Caulobacter crescentus cell cycle, and to analyze the evolutionary features of the cell cycle network.

Results

We used deep RNA sequencing to obtain high coverage RNA-Seq data of five C. crescentus cell cycle stages, each with three biological replicates. We found that 1,586 genes (over a third of the genome) display significant differential expression between stages. This gene list, which contains many genes previously unknown for their cell cycle regulation, includes almost half of the genes involved in primary metabolism, suggesting that these “house-keeping” genes are not constitutively transcribed during the cell cycle, as often assumed. Gene and module co-expression clustering reveal co-regulated pathways and suggest functionally coupled genes. In addition, an evolutionary analysis of the cell cycle network shows a high correlation between co-expression and co-evolution. Most co-expression modules have strong phylogenetic signals, with broadly conserved genes and clade-specific genes predominating different substructures of the cell cycle co-expression network. We also found that conserved genes tend to determine the expression profile of their module.

Conclusion

We describe the first phylogenetic and single-nucleotide-resolution transcriptomic analysis of a bacterial cell cycle network. In addition, the study suggests how evolution has shaped this network and provides direct biological network support that selective pressure is not on individual genes but rather on the relationship between genes, which highlights the importance of integrating phylogenetic analysis into biological network studies.

Keywords:
Cell cycle phylogenomics; Caulobacter crescentus; Co-expression network; Functional modules; Selective pressure