Genome Informatics 12: 398–399 (2001)
398
Relation between Restriction Modification Genes and Genome Rearrangements Suggested from Genome Sequence Comparison within Genus Neisseria Keiichirou Nakao3
Akito Chinen1
[email protected]
[email protected]
Ayaka Nobusato1
Youhei Fujitani3
Ikuo Uchiyama2
[email protected]
[email protected]
Ichizo Kobayashi1
[email protected] 1 2 3
Division of Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan Okazaki National Research Institutes, Nishigonaka 38, Myodaiji, Okazaki 444-8585, Japan Department of Applied Physics & Physico-Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kouhoku, Yokohama 223-8522, Japan
Keywords: genome evolution, genome rearrangement, mobile genetic element, genome comparison, selfish gene
1
Introduction
Restriction-modification (RM) gene complexes, such as EcoRI, encode two enzymatic functions, restriction and modification. A restriction enzyme will recognize a specific sequence in DNA and cut the DNA unless it is methylated by a cognate modification enzyme. RM systems will defend bacterial cells by attacking incoming foreign DNA. It is widely held that bacteria have evolved RM systems and maintain them in order to protect their genome from invasion by foreign DNA such as bacteriophages and plasmids. We found that a type II RM gene complex cannot be easily replaced by a competitor genetic element because cells that have lost the RM gene complex die through restriction enzyme attack on the chromosome [3, 6]. From this and other observations, we hypothesized that the relative frequency of RM gene complexes has increased through this post-segregational killing, in competitive exclusion, as well as through direct attack on invading DNA [4, 5]. The RM gene complexes are worth the name of selfish genes in the sense used in genetics and evolutionary biology. Horizontal transfer appears to be a general property of selfish genes. Indeed, there are various lines of evidence for their potential mobility and horizontal transfer [4]. The complete genome sequences of eubacteria and archaea (archaebacteria), especiallly those of closely related organisms, have been providing further evidence for their mobility and involvement in genome rearrangements. Comparison of two H. pylori genome sequences revealed that RM gene homologues are present at the end-point of an inversion and/or translocation at three loci [1]. Their comparison has suggested the presence of a mechanism for bacterial gene mobility - insertion with long target duplications - often associated with RMs [7]. Comparison of genome sequences of two different species in the genus Pyrococcus, hyperthermophilic archaeon (archaebacterium), revealed linkage of putative RM gene complexes with large genome polymorphisms — inversion and transposition [2]. In this communication, we compared three genome sequences belonging to Neisseria in a search for large genome polymorphisms linked with RM genes.
Relation between Restriction Modification Genes and Genome Rearrangements
2
399
Method and Results
The complete genome sequences of three different lines in the genus Neisseria, became available - those of Neisseria meningitidis strain Z2491 (serogroup A) [8, 11], Neisseria meningitidis strain MC58 (serogroup B) [9, 12], and Neisseria gonorrhoeae [13]. We searched these genomes for DNA methylase homologues and compared two genome sequences in their neighborhood by CGAT [10]. Each genome was characterized by abundance of highly repetitive elements. In intraspecific comparison, we identified insertion of an RM gene complex into an operon. We also identified insertion of a long DNA segment with an RM gene complex. In interspecific comparison, we identified transposition of RM gene complex and more examples of operon insertion. In some cases, the polymorphism is also linked with IS elements.
3
Discussion
These results lend further support for the hypothesis that RM genes are potentially mobile and involved in genome rearrangements [4].
References [1] Alm, R.A. et al., Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori, Nature, 397:176–80, 1999. [2] Chinen, A., Uchiyama, I., and Kobayashi, I., Comparison between Pyrococcus horikoshii and Pyrococcus abyssi genome sequences suggests association of restriction-modification genes with gross genome polymorphism, Gene, 259:109–121, 2000. [3] Handa, N., Nakayama, Y., Sadykov, M., and Kobayashi, I., Experimental genome evolution: large-scale genome rearrangements associated with resistance to replacement of a chromosomal restriction-modification gene complex., Mol. Microbiol., 40:932–940, 2001. [4] Kobayashi, I., Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution, Nucleic Acids Res., 29:3742–3756, 2001. [5] Kobayashi, I., DNA modification and restriction: selfish behavior of an epigenetic system, Epigenetic mechanisms of gene regulation, Cold Spring Harbor Laboratory Press, 155–172, 1996. [6] Naito, T., Kusano, K., and Kobayashi, I., Selfish behavior of restriction-modification systems., Science, 267:897–899, 1995. [7] Nobusato, A., Uchiyama, I., Ohashi, S., and Kobayashi, I., Insertion with long target duplications: a mechanism for gene mobility suggested from comparison of two related bacterial genomes, Gene, 259:99–108, 2000. [8] Parkhill, J. et al., Complete DNA sequence of a serogroup A strain of Neisseria menigitidis Z2491, Nature, 404:502–506, 2000. [9] Tettelin, H. et al., Complete genome sequence of Neisseria meningitidis serogroup B strain MC58, Science, 287:1767–1768, 2000. [10] Uchiyama, I., Higuchi, T., and Kobayashi, I., CGAT: Comparative Genome Analysis Tool for closely related microbial genomes. Genome Informatics, 11:341–343, 2000. [11] http://www.sanger.ac.uk/Projects/N meningitidis/ [12] http://www.tigr.org/tigr-scripts/CMR2/GenomePage3.spl?database=gnm [13] http://dna1.chem.ou.edu/gono.html
