The search for a systematic catalog of auxiliary metabolic genes (AMGs) within marine viruses goes back over 20 years. The story of AMGs in viruses can be traced back to Sullivan's days as a graduate student and Debbie Lindell's time as a postdoc in the Chisholm lab at MIT, when he inadvertently identified photosynthesis genes in cyanophages (viruses that infect cyanobacteria) and thought they were contamination in the genomes. Debbie immediately saw them as a signature of co-evolution¹. Debbie later showed that these genes were indeed transcribed and translated during infection^2,3, which Jason Bragg then modeled physiological differences⁴. 

In the decades since sequencing technology and analytic advances have driven a surge in AMG studies across various ecosystems. Yet the lack of a systematically curated AMG catalog remained, thus hindering the integration of viruses into models to quantitatively assess their metabolic and biogeochemical impacts. Fortunately, five years prior to this study, global dsDNA catalog papers began to be published^5,6,7, resulting in the identification of over 190,000 dsDNA viruses across the global oceans. For the first time, this presented a global ocean dataset that was deeply sequenced and curated for dsDNA viruses. It was against this backdrop that Funing Tian, then a PhD student in Microbiology who had received a University Fellowship from The Ohio State University, and James Wainaina, having just completed his graduate studies at the University of Western Australia (UWA), began working on this project. 

Funing Tian (Left), Zhiping Zhong (Center), and James Wainaina (Right) during a poster presentation of the global AMG catalog work at the Center of Microbiome Science (CoMS) MidWest Conference May 2022

The Ocean AMG project faced numerous challenges. First, despite the increase in AMG studies, the lack of standards for what constitutes a 'bona fide' AMG has prevented cross-study comparisons. This necessitated the development of standards for what could be 'conservatively' assigned as AMGs, a process that took almost a year and was further aided by new analytical tools by Kelly Wrighton lab⁸. After identifying ~22,000 AMG gene clusters, the second challenge was determining how to narrow down to the most biogeochemical important AMGs, without "cherry-picking" the dataset, this was the most challenging part of the project. We tried over half a dozen approaches to select a subset of biologically relevant AMGs that would be sufficient to highlight and discuss. We eventually focused on a few based on their metabolic functions, thanks in part to colleagues and co-authors (Cristina Howard-Verona and Garrett Smith) in the Sullivan lab as well, as co-author Steven Hallam, who had strong 'metabolic brains.' However, we confess we have just but scratched the surface of this catalog. Since the data is publicly available, it provides the scientific community with a catalog they can explore further. We look forward to the numerous subplots this dataset will reveal in the coming years, especially important in unraveling the role of viruses in ocean biogeochemical processes that has remained elusive to quantify.

There are several take-home messages from this paper. Firstly, given the avalanche of data from large consortia such as the Tara Ocean Expedition, it is crucial to have a systematic and scalable approach for analyzing the data and enabling cross-study comparisons. Secondly, reliable, updated, and maintained viral ecogenomics tools will be essential for continuously exploring and advancing omic data sets, especially within the marine ecosystem. Finally, this study would not have been possible without cross-disciplinary collaboration, teamwork, dogged determination despite scientific challenges, and an unwavering spirit; this was particularly important as it took over four years to get this work to publication.

What does the future hold for us, Funing Tian, now Dr. Tian is currently a Bioinformatician at the University of Chicago, where she focuses on bioinformatics analysis of single-cell multi-omics sequencing for asthma research. James has started his research group at the Woods Hole Oceanographic Institution Biology Department, where he  continues exploring the ecology and evolution of marine viruses with a particular focus on corals.

 Reference:

1.        Sullivan, M. B. et al. Prevalence and Evolution of Core Photosystem II Genes in Marine Cyanobacterial Viruses and Their Hosts. PLoS Biol. 4, e234 (2006).

2.        Lindell, D. et al. Transfer of photosynthesis genes to and from Prochlorococcus viruses. Proc. Natl. Acad. Sci. U. S. A. 101, 11013–11018 (2004).

3.        Lindell, D., Jaffe, J. D., Johnson, Z. I., Church, G. M. & Chisholm, S. W. Photosynthesis genes in marine viruses yield proteins during host infection. Nature 438, 86–89 (2005).

4.        Bragg, J. G. & Chisholm, S. W. Modeling the fitness consequences of a cyanophage-encoded photosynthesis gene. PLoS One 3, 1–9 (2008).

5.        Brum, J. R. et al. Ocean Viral Communities. Science (80-. ). 348, 1261498-1–11 (2015).

6.        Roux, S. et al. Ecogenomics and potential biogeochemical impacts of globally abundant ocean viruses. Nature 537, 689–693 (2016).

7.        Gregory, A. C. et al. Marine DNA Viral Macro- and Microdiversity from Pole to Pole. Cell 177, 1109-1123.e14 (2019).

8.        Shaffer, M. et al. DRAM for distilling microbial metabolism to automate the curation of microbiome function. Nucleic Acids Res. 48, 8883–8900 (2020).