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Genomic context analysis in Archaea suggests previously unrecognized links between DNA replication and translation

Jonathan Berthon12*, Diego Cortez3 and Patrick Forterre13*

Author Affiliations

1 Univ. Paris-Sud 11, CNRS, UMR8621, Institut de Génétique et Microbiologie, 91405 Orsay CEDEX, France

2 Laboratory of Protein Chemistry and Engineering, Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka-shi, Fukuoka 812-8581, Japan

3 Institut Pasteur, rue Dr. Roux, 75724 Paris CEDEX 15, France

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Genome Biology 2008, 9:R71  doi:10.1186/gb-2008-9-4-r71

Published: 9 April 2008

Abstract

Background

Comparative analysis of genomes is valuable to explore evolution of genomes, deduce gene functions, or predict functional linking between proteins. Here, we have systematically analyzed the genomic environment of all known DNA replication genes in 27 archaeal genomes to infer new connections for DNA replication proteins from conserved genomic associations.

Results

Two distinct sets of DNA replication genes frequently co-localize in archaeal genomes: the first includes the genes for PCNA, the small subunit of the DNA primase (PriS), and Gins15; the second comprises the genes for MCM and Gins23. Other genomic associations of genes encoding proteins involved in informational processes that may be functionally relevant at the cellular level have also been noted; in particular, the association between the genes for PCNA, transcription factor S, and NudF. Surprisingly, a conserved cluster of genes coding for proteins involved in translation or ribosome biogenesis (S27E, L44E, aIF-2 alpha, Nop10) is almost systematically contiguous to the group of genes coding for PCNA, PriS, and Gins15. The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis. Interestingly, the gene encoding the S27E protein, also known as metallopanstimulin 1 (MPS-1) in human, is overexpressed in multiple cancer cell lines.

Conclusion

Our genome context analysis suggests specific functional interactions for proteins involved in DNA replication between each other or with proteins involved in DNA repair or transcription. Furthermore, it suggests a previously unrecognized regulatory network coupling DNA replication and translation in Archaea that may also exist in Eukarya.