Shakya, M. | Search bioRxiv

bioRxiv2017

Hi-C deconvolution of a human gut microbiome yields high-quality draft genomes and reveals plasmid-genome interactions.

The assembly of high-quality genomes from mixed microbial samples is a long-standing challenge in genomics and metagenomics. Here, we describe the application of ProxiMeta, a Hi-C-based metagenomic deconvolution method, to deconvolve a human fecal metagenome. This method uses the intra-cellular proximity signal captured by Hi-C as a direct indicator of which sequences originated in the same cell, enabling culture-free de novo deconvolution of mixed genomes without any reliance on a priori information. We show that ProxiMeta deconvolution provides results of markedly high accuracy and sensitivity, yielding 50 near-complete microbial genomes (many of which are novel) from a single fecal sample, out of 252 total genome clusters. ProxiMeta outperforms traditional contig binning at high-quality genome reconstruction. ProxiMeta shows particularly good performance in constructing high-quality genomes for diverse but poorly-characterized members of the human gut. We further use ProxiMeta to reconstruct genome plasmid content and sharing of plasmids among genomes--tasks that traditional binning methods usually fail to accomplish. Our findings suggest that Hi-C-based deconvolution can be useful to a variety of applications in genomics and metagenomics.

genomics↗

bioRxiv2017

Insights into Origin and Evolution of α-proteobacterial Gene Transfer Agents

Several bacterial and archaeal lineages produce nanostructures that morphologically resemble small tailed viruses, but, unlike most viruses, contain apparently random pieces of the host genome. Since these elements can deliver the packaged DNA to other cells, they were dubbed Gene Transfer Agents (GTAs). Because many genes involved in GTA production have viral homologs, it has been hypothesized that the GTA ancestor was a virus. Whether GTAs represent an atypical virus, a defective virus, or a virus co-opted by the prokaryotes for some function, remains to be elucidated. To evaluate these possibilities, we examined the distribution and evolutionary histories of genes that encode a GTA in the -proteobacterium Rhodobacter capsulatus (RcGTA). We report that although homologs of many individual RcGTA genes are abundant across bacteria and their viruses, RcGTA-like genomes are mainly found in one subclade of -proteobacteria. When compared to the viral homologs, genes of the RcGTA-like genomes evolve significantly slower, and do not have higher %A+T nucleotides than their host chromosomes. Moreover, they appear to reside in stable regions of the bacterial chromosomes that are generally conserved across taxonomic orders. These findings argue against RcGTA being an atypical or a defective virus. Our phylogenetic analyses suggest that RcGTA ancestor likely originated in the lineage that gave rise to contemporary -proteobacterial orders Rhizobiales, Rhodobacterales, Caulobacterales, Parvularculales, and Sphingomonadales, and since that time the RcGTA-like element has co-evolved with its host chromosomes. Such evolutionary history is compatible with maintenance of these elements by bacteria due to some selective advantage. As for many other prokaryotic traits, horizontal gene transfer played a substantial role in the evolution of RcGTA-like elements, not only in shaping its genome components within the orders, but also in occasional dissemination of RcGTA-like regions across the orders and even to different bacterial phyla.

evolutionary biology↗