Sequence permutations in the molecular evolution of DNA methyltransferases

Area of Science:

• Molecular Biology
• Genetics
• Enzymology

Background:

• DNA methyltransferases (MTases) display unique sequence permutations, unlike other MTases.
• Known DNA MTases are classified into alpha, beta, and gamma classes, with limited known members in zeta and no identified members in delta and epsilon classes.
• Permutation mechanisms include gene duplication, in-frame fusion, and gene segment shuffling.

Purpose of the Study:

• To identify novel classes of permuted DNA methyltransferases.
• To investigate the evolutionary origins of identified delta and zeta class DNA MTases.
• To elucidate the mechanisms driving sequence permutation in DNA MTases.

Main Methods:

• Bioinformatic analysis of DNA methyltransferase sequences.
• Comparative genomics to identify novel MTase classes.
• Phylogenetic analysis to infer evolutionary relationships.

Main Results:

• Discovery of two novel DNA MTase classes: delta and zeta.
• Identification of M.MwoI as the first delta-class MTase and M.TvoORF1413P as the second zeta-class MTase.
• Evidence suggests delta and zeta class MTases evolved from beta-class MTases, with delta being the first identified of its class and zeta being the first in the DNA:m4C and m6A-MTase groups.

Conclusions:

• Gene fragmentation and reassembly, driven by factors like nuclease attack during restriction-modification system invasion, can lead to permuted DNA MTases.
• "Cut-and-paste" mechanism proposed for beta-delta permutation, involving non-circular gene segment relocation.
• Circular beta-zeta permutation can be explained by gene duplication or fragment shuffling, with both mechanisms potentially contributing to permuted DNA MTase evolution.