Paper on bacterial DNA methyltransferases in Nucleic Acids Research

Our paper describing a comparative genomic study of DNA methyltransferases in bacteria has appeared online in Nucleic Acids Research. The work was motivated by discussions with Sandeep Krishna and was ably supported by Parul Singh. 

To quote from the paper abstract: 

DNA methytransferases (MTs) in bacteria are best understood in the context of restriction–modification (R–M) systems, which act as bacterial immune systems against incoming DNA including phages, but have also been described as selfish elements. But several orphan MTs, which are not associated with any restriction enzyme, have also been characterized and may protect against parasitism by R–M systems. The occurrence of MTs in these two contexts, namely as part of R–M systems or as orphans, is poorly understood. Here we report the results of a comparative genomic survey of DNA MTs across ∼1000 bacterial genomes. We show that orphan MTs overwhelm R–M systems in their occurrence. In general, R–M MTs are poorly conserved, whereas orphans are nearly as conserved within a genus as any average gene. However, oligonucleotide usage and conservation patterns across genera suggest that both forms of MTs might have been horizontally acquired. We suggest that many orphan MTs might be ‘degradation’ products of R–M systems, based on the properties of orphan MTs encoded adjacent to highly diverged REs. In addition, several fully degraded R–M systems exist in which both the MT and the RE are highly divergent from their corresponding reference R–M pair. Despite their sporadic occurrence, conserved R–M systems are present in strength in two highly transformable genera, in which they may contribute to selection against integration of foreign DNA. 

The paper is available online.

In Plain English for the busy:

DNA - a complex structure - consists of four building blocks

Specific modifications occur some of these blocks; 'methylation' of a block called 'cytosine' is one such example

These modifications are done by proteins called methyltransferases (MTs) and they methylate a block only if it is present in a particular sequence of blocks (for example the block 'A' in the sequence GATC)

These MTs generally go along with a scissor protein called restriction enzyme (RE) that will cut the DNA at the same sequence recognised by the MT - but be inactive if the block has been modified by the MT

In a bacterium, its own DNA is kept in a methylated state, and is not cut. But when a parasite DNA shows up and is not methylated, the RE destroys it. Sounds like our immune system.

But MT-RE pairs are also selfish elements that preserve themselves by killing cells that somehow lose them from their genetic material.

However, in many cases only the MT exists; the RE, which on its own is toxic to the cell, is missing. These MTs are called 'solitary' or 'orphans'.

Our work shows that - 

- many MTs are solitary

- RE-MT pairs are not 'indigenous' to the host; they are freelancers that selfishly establish themselves in a host

- solitary MTs might emerge from selective degradation of the DNA portion originally encoding the toxic RE; the solitary MT is no longer selfish and may subsequently develop interesting functions [1][2]

We are funded by NCBS (DAE), DST, CSIR, DBT. and UGC