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, 32 (3), 1050-8

Biased Distribution of DNA Uptake Sequences Towards Genome Maintenance Genes

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Biased Distribution of DNA Uptake Sequences Towards Genome Maintenance Genes

Tonje Davidsen et al. Nucleic Acids Res.

Abstract

Repeated sequence signatures are characteristic features of all genomic DNA. We have made a rigorous search for repeat genomic sequences in the human pathogens Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae and found that by far the most frequent 9-10mers residing within coding regions are the DNA uptake sequences (DUS) required for natural genetic transformation. More importantly, we found a significantly higher density of DUS within genes involved in DNA repair, recombination, restriction-modification and replication than in any other annotated gene group in these organisms. Pasteurella multocida also displayed high frequencies of a putative DUS identical to that previously identified in H.influenzae and with a skewed distribution towards genome maintenance genes, indicating that this bacterium might be transformation competent under certain conditions. These results imply that the high frequency of DUS in genome maintenance genes is conserved among phylogenetically divergent species and thus are of significant biological importance. Increased DUS density is expected to enhance DNA uptake and the over-representation of DUS in genome maintenance genes might reflect facilitated recovery of genome preserving functions. For example, transient and beneficial increase in genome instability can be allowed during pathogenesis simply through loss of antimutator genes, since these DUS-containing sequences will be preferentially recovered. Furthermore, uptake of such genes could provide a mechanism for facilitated recovery from DNA damage after genotoxic stress.

Figures

Figure 1
Figure 1
Designation of DUS overlapping and DUS-associated sequences, as exemplified by the Neisseria DUS. The DNA uptake sequence 5′-GGCCGTCTGAA-3′ is marked in red. Oligomers that physically overlap with the DUS are termed DUS-overlapping sequences and are marked in blue. Oligomers that are mutated in one or more of the 10 bp DUS (green denotes the mutation in the examples given) are called DUS-like sequences and are marked in orange. DUS overlapping each other with one DUS located on each strand were not detected (the Neisseria sp.) or could not occur (H.influenzae). DUS-overlapping sequences were excluded from the analysis, while the DUS-like sequences were included among the control sequences.
Figure 2
Figure 2
The most frequent oligonucleotides (9- and 10mers) containing all four nucleotides in the CDS of N.meningitidis Z2491, N.meningitidis MC58, N.gonorrhoeae FA1090, H.influenzae KW20, P.multocida PM70 and E.coli K12 were counted; E.coli K12 is included to illustrate the distribution in a negative control. DUS denotes either the neisserial 10 bp DUS or the H.influenzae 9 bp DUS. The length of the bars represent the number of DUS found in CDS. The bar is split into the expected number (red) and the abundance (blue), which is the actual number found minus the expected number. DUS and DUS-overlapping sequences (see Fig. 1) were counted separately and illustrated as the shaded areas; the solid areas illustrate oligonucleotide counts if DUS were masked before counting.

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