Avoidance of palindromic words in bacterial and archaeal genomes: A close connection with restriction enzymes

Mikhail S. Gelfand, Eugene V. Koonin

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109 Citations (Scopus)


Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a statistically significant level in the genomes of several bacteria, including the completely sequenced Haemophilus influenzae and Synechocystis sp. genomes and in the complete genome of the archaeon Methanococcus jannaschii. In contrast, there is only moderate avoidance of palindromes in the small genome of the bacterium Mycoplasma genitalium and no detectable avoidance in the genomes of chloroplasts and mitochondria. The sites for type II restriction-modification enzymes detected in the given species tend to be among the most avoided palindromes in a particular genome, indicating a direct connection between the avoidance of short oligonucleotide words and restriction-modification systems with the respective specificity. Palindromes corresponding to sites for restriction enzymes from other species are also avoided, albeit less significantly, suggesting that in the course of evolution bacterial DNA has been exposed to a wide spectrum of restriction enzymes, probably as the result of lateral transfer mediated by mobile genetic elements, such as plasmids and prophages. Palindromic words appear to accumulate in DNA once it becomes isolated from restriction-modification systems, as demonstrated by the case of organellar genomes. By combining these observations with protein sequence analysis, we show that the most avoided 4-palindrome and the most avoided 6-palindrome in the archaeon M. jannaschii are likely to be recognition sites for two novel restriction-modification systems.

Original languageEnglish
Pages (from-to)2430-2439
Number of pages10
JournalNucleic Acids Research
Issue number12
Publication statusPublished - 1997
Externally publishedYes


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