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Metagenomic methylation patterns resolve bacterial genomes of unusual size and structural complexity - Easy Microbial Genomics

Home > Paper Highlights >  Metagenomic methylation patterns resolve bacterial genomes of unusual size and structural complexity

Metagenomic methylation patterns resolve bacterial genomes of unusual size and structural complexity

Posted April 24, 2022

In our nucleotide and protein sequence databases, we have neat static sequence of letters. However, in nature, the bacterial and archaeal genomes are far different from them. They are alive-with all the dynamism and complexity we relate to life. The genome is catalyzed by homologous recombination, mobile genetic elements, bacteriophage intragenome and intergenomic shuffling, and can undergo significant changes throughout the life cycle of a single cell. Unlike the gradual accumulation of point mutations, this bulk rearrangement can suddenly diversify the phenotypic characteristics of an organism and change its ecological niche.

The plasticity of the bacterial and archaeal genomes makes their ecological and evolutionary dynamics research exciting, but the same mechanisms that enable rapid genomic change and adaptation disrupt our current approaches to recovering the complete genome from metagenomics (genome binning).

The research group of Dr Elizabeth Wilbanks from University of California challenged genome binning and used strain-specific DNA methylation patterns to solve complex bacterial genomes from long-read metagenomic data from marine microbial communities (“pink berries” in Shippewiset Wetlands, USA). A unique combination of bacterially encoded restriction modification (RM) systems provides a unique methylation profile for accurate classification and classification of metagenomic sequences. Using this approach, they completed the largest and most complex circular bacterial genome recovered from the metagenomics, the complete genome of sulforaphane PB-PSB1 (7.9 Mb,> 600 transposons), which is the major bacterium of the flora. From the genome binned by the methylation pattern, they identified examples of horizontal gene transfer, phage infection, and strain-level structural mutations between the sulfur cycle symbiont (Thiohalocapsasp. PB-PSB1 and Desulfofustissp. PB-SRB1). They also associated the methylation patterns of each genome assembled in the metagenome with the encoded DNA methyltransferases and discovered new RM defense systems, including new associations between the RM system and RNase toxins.


Contigs clustered by methylation profiles, compared to that by tetranucleotide frequency profiles

image source: ISME J

Reference

Wilbanks, E.G., Doré, H., Ashby, M.H. et al. Metagenomic methylation patterns resolve bacterial genomes of unusual size and structural complexity. ISME J (2022). https://doi.org/10.1038/s41396-022-01242-7