Abstract

Restriction–modification (RM) systems in bacteria are implicated in multiple biological roles ranging from defense against parasitic genetic elements, to selfish addiction cassettes, and barriers to gene transfer and lineage homogenization. In bacteria, DNA-methylation without cognate restriction also plays important roles in DNA replication, mismatch repair, protein expression, and in biasing DNA uptake. Little is known about archaeal RM systems and DNA methylation. To elucidate further understanding for the role of RM systems and DNA methylation in Archaea, we undertook a survey of the presence of RM system genes and related genes, including orphan DNA methylases, in the halophilic archaeal class Halobacteria. Our results reveal that some orphan DNA methyltransferase genes were highly conserved among lineages indicating an important functional constraint, whereas RM systems demonstrated patchy patterns of presence and absence. This irregular distribution is due to frequent horizontal gene transfer and gene loss, a finding suggesting that the evolution and life cycle of RM systems may be best described as that of a selfish genetic element. A putative target motif (CTAG) of one of the orphan methylases was underrepresented in all of the analyzed genomes, whereas another motif (GATC) was overrepresented in most of the haloarchaeal genomes, particularly in those that encoded the cognate orphan methylase.

Highlights

  • DNA methyltransferases (MTases) are enzymes which catalyze the addition of a methyl group to a nucleotide base in a DNA molecule

  • Our analysis shows that most of the collapsed HG (cHG) are found more than once. (Figure 1A)

  • 16 families are found in 20 or more genomes each (>9%), and this frequency steadily increases culminating in five families being conserved in greater than 80 genomes each (>37%) with one cHG being in ~80% of all Haloarchaea surveyed

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Summary

Introduction

DNA methyltransferases (MTases) are enzymes which catalyze the addition of a methyl group to a nucleotide base in a DNA molecule. These enzymes will methylate either adenine, producing N6-methyladenine (6mA), or cytosine, producing either N4-methylcytosine (4mC) or. DNA methyltransferases typically consist of three types of protein domains: an S-adenosyl-L-methionine (AdoMet) binding domain which obtains the methyl group from the cofactor AdoMet, a target recognition domain (TRD). That binds the enzyme to the DNA strand at a short nucleotide sequence known as the recognition sequence, and a catalytic domain that transfers the methyl group from AdoMet to a nucleotide at the recognition sequence [2]. RM systems have been described as addiction cassettes akin to toxin-antitoxin systems, in which postsegregational killing occurs when the RM system is lost since the MTase activity degrades more quickly than

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