Bringing the viral "unknown" to light through wild community and model system characterization
EMSL Project ID
47930
Abstract
Ocean microbes drive the biogeochemistry that fuels the planet, and their viruses impact microbes through mortality, horizontal gene transfer, and directly manipulating microbial metabolisms. However, our understanding of viral roles in global biogeochemistry and ecosystem processes is bottlenecked by severe technical limitations. Most relevant here is that few viruses have been cultivated, but culture-independent methods (e.g., meta-genomics) result in sequence reads that are predominantly "unknown", often dominating (to 95%) the data [1-5]. We have now analyzed 35M reads from 40 viral metagenomes (viromes) to prepare 11 manuscripts now published [6-11] or in review [12-16]. This has led to development of a quantitative sample-to-sequence viral metagenomic pipeline [7-9, 17] that has enabled myriad discoveries, including uncovering the most abundant viruses in the oceans [18], as well as informatic solutions to organize unknown viral sequence space [10]. Given this organization, we revealed that the "core" Pacific Ocean virome is made of only 180 proteins, that its pan-genome is relatively well sampled (~422k proteins), and that the bulk of these proteins -- even those "core" to all samples -- are functionally unknown, but abundant, and presumably driving viral effects on ecosystem function [14]. Further, these new datasets suggest that viruses manipulate all of central microbial metabolism during infection [13], which extends viral roles in global carbon cycling well beyond lysis and cyanophage manipulation of photosynthesis (see below). Here we propose two specific aims to reduce viral unknown sequence space and to provide fundamental knowledge for predictive biological modeling (technical details summarized in addendum): Aim 1. Virion structural metaproteomics of 20 viral communities where quantitative viromes and community morphological characterization are already available Aim 2. Structural characterization (cryo-electron microscopy) of 3 novel ocean viral isolates and time-resolved virus-host infection dynamics (transcriptomics, proteomics, metabolomics) of 5 ocean viral isolates -- all of which are represented in metagenomes mostly by proteins of unknown function The proposed work fits multiple aspects of EMSL's "Biological Interactions and Dynamics" theme including: (i) identifying functions for uncharacterized genes to help model structure-function relationships of biological proteins; (ii) illuminating connections between biological oscillators (e.g., viruses and their hosts), metabolites, pathways, gene and protein regulation and the global carbon cycle; (iii) systems biology data needed for predictive biological modeling of the intracellular dynamics of diverse phage-host interactions. EMSL offers the perfect collaborative opportunity to leverage our extensive sample archive and ecologically important model system development with unprecedented, cutting-edge analytical capabilities all under one roof. Successful data generation will be valuable both directly to the particular proposed studies, as well as broadly to all virome studies drowning in "the unknown".
Project Details
Project type
Large-Scale EMSL Research
Start Date
2013-10-01
End Date
2016-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members
Related Publications
Cristina Howard-Varona1-, Simon Roux1, Hugo Dore2, Natalie Solonenko1, Karin Holmfeldt3, Lye M. Markillie4, Galya Orr4 & Matthew B. Sullivan1
Cristina Howard-Varona, Katherine R. Hargreaves, Natalie E. Solonenko, Lye M. Markillie, Richard Allen White III, Heather M. Brewer, Charles Ansong, Galya Orr, Joshua N. Adkins & Matthew B. Sullivan
Howard-Varona C., K.R. Hargreaves, N.E. Solonenko, L. Markillie, R.A. White, H.M. Brewer, and C.K. Ansong, et al. 2018. "Multiple mechanisms drive phage infection efficiency in nearly-identical hosts." International Society of Microbial Ecology 12. PNNL-SA-132683. doi:10.1038/s41396-018-0099-8
Howard-Varona C, S Roux, H Dore, NE Solonenko, KM Holmfeldt, LM Markillie, G Orr, and MB Sullivan. 2017. "Regulation of infection efficiency in a globally abundant marine Bacteriodetes virus." The ISME Journal 11(1):284-295. doi:10.1038/ismej.2016.81