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

Berthon J, Cortez D, Forterre P - Genome Biol. (2008)

Bottom Line: The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Univ. Paris-Sud 11, CNRS, UMR8621, Institut de Génétique et Microbiologie, 91405 Orsay CEDEX, France. jonathan.berthon@igmors.u-psud.fr

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.

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Conserved genomic context of three DNA replication genes in archaeal genomes. This figure highlights the genome context of three DNA replication genes that recurrently associate with a particular set of genes in archaeal genomes (for a detailed picture of the genome context of all DNA replication genes examined in this study see Additional data file 2). (a) The gene encoding Gins15 is linked to the gene coding for PCNA and to the gene for the small subunit of the primase in all crenarchaeal genomes, whereas it is alternatively linked to one of these two genes in most euryarchaeal genomes. (b) The gene for the PCNA associates with the genes encoding the small or the large subunit of the DNA primase. It is also frequently linked to the gene encoding TFS and/or to the gene coding for the ADP-ribose pyrophosphatase NudF. (c) The gene encoding the MCM helicase is contiguous to the gene for Gins23 and/or to the gene for the beta subunit of the initiation factor aIF-2 in several archaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.
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Figure 2: Conserved genomic context of three DNA replication genes in archaeal genomes. This figure highlights the genome context of three DNA replication genes that recurrently associate with a particular set of genes in archaeal genomes (for a detailed picture of the genome context of all DNA replication genes examined in this study see Additional data file 2). (a) The gene encoding Gins15 is linked to the gene coding for PCNA and to the gene for the small subunit of the primase in all crenarchaeal genomes, whereas it is alternatively linked to one of these two genes in most euryarchaeal genomes. (b) The gene for the PCNA associates with the genes encoding the small or the large subunit of the DNA primase. It is also frequently linked to the gene encoding TFS and/or to the gene coding for the ADP-ribose pyrophosphatase NudF. (c) The gene encoding the MCM helicase is contiguous to the gene for Gins23 and/or to the gene for the beta subunit of the initiation factor aIF-2 in several archaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.

Mentions: Since DNA replication proteins should interact physically and/or functionally in the replication factory, one can expect that genes encoding different DNA replication proteins sometimes co-localize in archaeal genomes, as a blueprint for these interactions. Such DNA replication islands were previously observed in the vicinity of the Pyrococcus abyssi chromosomal replication origin (oriC), where the gene encoding Cdc6 lies together with those encoding DP1, DP2, RFC-s, and RFC-l [22]; and at the cdc6-2 locus in Sulfolobus solfataricus, where the genes encoding RFC-s, RFC-l, Cdc6-2, Gins23, and MCM are situated [23,24]. We have detected several new DNA replication islands in our analysis. The association of the genes encoding PCNA, PriS, and Gins15 (hereafter called the PPsG cluster), previously observed by others [14,24], is the most conserved clustering. The full PPsG cluster is not conserved across the entire archaeal domain since the three corresponding genes are adjacent only in crenarchaeal genomes, but the gene encoding Gins15 is contiguous to either the gene for PCNA or the gene for PriS in most euryarchaeal genomes, strongly suggesting that Gins15, PCNA, and PriS functionally associate (Figure 2a). Hence, the genes encoding Gins15 and PCNA are direct neighbors in the four Thermococcales, in two Methanococcales, and in two Methanobacteriales, whereas the genes encoding Gins15 and PriS are adjacent in Methanosarcinales (four species) and in halophilic Archaea (three species). Interestingly, while the gene encoding PCNA is an immediate neighbor of PriS in the PPsG cluster, it co-localizes with the gene encoding the other primase subunit, PriL, in the four Methanosarcinales, in A. fulgidus, Haloarcula marismortui, and Halobacterium salinarum (Figure 2b). In summary, the gene encoding Gins15 is associated with the genes encoding PriS and PCNA (Crenarchaea) or contiguous to one of these two genes (Euryarchaea), whilst the gene coding for PCNA is linked either to the gene encoding PriS (Crenarchaea) or to the gene coding for PriL (Euryarchaea) (Figure 2a,b). This suggests that PCNA could interact with the two primase subunits, whereas Gins15 could interact directly with PCNA and PriS. Finally, the gene encoding Gins23, which has been detected only in Crenarchaea and Thermococcales, neighbors the gene encoding MCM in all these Archaea, except in P. aerophilum (Figure 2c).


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

Berthon J, Cortez D, Forterre P - Genome Biol. (2008)

Conserved genomic context of three DNA replication genes in archaeal genomes. This figure highlights the genome context of three DNA replication genes that recurrently associate with a particular set of genes in archaeal genomes (for a detailed picture of the genome context of all DNA replication genes examined in this study see Additional data file 2). (a) The gene encoding Gins15 is linked to the gene coding for PCNA and to the gene for the small subunit of the primase in all crenarchaeal genomes, whereas it is alternatively linked to one of these two genes in most euryarchaeal genomes. (b) The gene for the PCNA associates with the genes encoding the small or the large subunit of the DNA primase. It is also frequently linked to the gene encoding TFS and/or to the gene coding for the ADP-ribose pyrophosphatase NudF. (c) The gene encoding the MCM helicase is contiguous to the gene for Gins23 and/or to the gene for the beta subunit of the initiation factor aIF-2 in several archaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2643942&req=5

Figure 2: Conserved genomic context of three DNA replication genes in archaeal genomes. This figure highlights the genome context of three DNA replication genes that recurrently associate with a particular set of genes in archaeal genomes (for a detailed picture of the genome context of all DNA replication genes examined in this study see Additional data file 2). (a) The gene encoding Gins15 is linked to the gene coding for PCNA and to the gene for the small subunit of the primase in all crenarchaeal genomes, whereas it is alternatively linked to one of these two genes in most euryarchaeal genomes. (b) The gene for the PCNA associates with the genes encoding the small or the large subunit of the DNA primase. It is also frequently linked to the gene encoding TFS and/or to the gene coding for the ADP-ribose pyrophosphatase NudF. (c) The gene encoding the MCM helicase is contiguous to the gene for Gins23 and/or to the gene for the beta subunit of the initiation factor aIF-2 in several archaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.
Mentions: Since DNA replication proteins should interact physically and/or functionally in the replication factory, one can expect that genes encoding different DNA replication proteins sometimes co-localize in archaeal genomes, as a blueprint for these interactions. Such DNA replication islands were previously observed in the vicinity of the Pyrococcus abyssi chromosomal replication origin (oriC), where the gene encoding Cdc6 lies together with those encoding DP1, DP2, RFC-s, and RFC-l [22]; and at the cdc6-2 locus in Sulfolobus solfataricus, where the genes encoding RFC-s, RFC-l, Cdc6-2, Gins23, and MCM are situated [23,24]. We have detected several new DNA replication islands in our analysis. The association of the genes encoding PCNA, PriS, and Gins15 (hereafter called the PPsG cluster), previously observed by others [14,24], is the most conserved clustering. The full PPsG cluster is not conserved across the entire archaeal domain since the three corresponding genes are adjacent only in crenarchaeal genomes, but the gene encoding Gins15 is contiguous to either the gene for PCNA or the gene for PriS in most euryarchaeal genomes, strongly suggesting that Gins15, PCNA, and PriS functionally associate (Figure 2a). Hence, the genes encoding Gins15 and PCNA are direct neighbors in the four Thermococcales, in two Methanococcales, and in two Methanobacteriales, whereas the genes encoding Gins15 and PriS are adjacent in Methanosarcinales (four species) and in halophilic Archaea (three species). Interestingly, while the gene encoding PCNA is an immediate neighbor of PriS in the PPsG cluster, it co-localizes with the gene encoding the other primase subunit, PriL, in the four Methanosarcinales, in A. fulgidus, Haloarcula marismortui, and Halobacterium salinarum (Figure 2b). In summary, the gene encoding Gins15 is associated with the genes encoding PriS and PCNA (Crenarchaea) or contiguous to one of these two genes (Euryarchaea), whilst the gene coding for PCNA is linked either to the gene encoding PriS (Crenarchaea) or to the gene coding for PriL (Euryarchaea) (Figure 2a,b). This suggests that PCNA could interact with the two primase subunits, whereas Gins15 could interact directly with PCNA and PriS. Finally, the gene encoding Gins23, which has been detected only in Crenarchaea and Thermococcales, neighbors the gene encoding MCM in all these Archaea, except in P. aerophilum (Figure 2c).

Bottom Line: The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Univ. Paris-Sud 11, CNRS, UMR8621, Institut de Génétique et Microbiologie, 91405 Orsay CEDEX, France. jonathan.berthon@igmors.u-psud.fr

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.

Show MeSH
Related in: MedlinePlus