A Caltech Library Service

Synergistic epistasis enhances the co-operativity of mutualistic interspecies interactions

Turkarslan, Serdar and Stopnisek, Nejc and Thompson, Anne W. and Arens, Christina E. and Valenzuela, Jacob J. and Wilson, James and Hunt, Kristopher A. and Hardwicke, Jessica and López García de Lomana, Adrián and Lim, Sujung and Seah, Yee Mey and Fu, Ying and Wu, Liyou and Zhou, Jizhong and Hillesland, Kristina L. and Stahl, David A. and Baliga, Nitin S. (2021) Synergistic epistasis enhances the co-operativity of mutualistic interspecies interactions. ISME Journal, 15 (8). pp. 2233-2247. ISSN 1751-7362. PMCID PMC8319347. doi:10.1038/s41396-021-00919-9.

[img] PDF - Published Version
Creative Commons Attribution.

[img] PDF - Supplemental Material
Creative Commons Attribution.


Use this Persistent URL to link to this item:


Early evolution of mutualism is characterized by big and predictable adaptive changes, including the specialization of interacting partners, such as through deleterious mutations in genes not required for metabolic cross-feeding. We sought to investigate whether these early mutations improve cooperativity by manifesting in synergistic epistasis between genomes of the mutually interacting species. Specifically, we have characterized evolutionary trajectories of syntrophic interactions of Desulfovibrio vulgaris (Dv) with Methanococcus maripaludis (Mm) by longitudinally monitoring mutations accumulated over 1000 generations of nine independently evolved communities with analysis of the genotypic structure of one community down to the single-cell level. We discovered extensive parallelism across communities despite considerable variance in their evolutionary trajectories and the perseverance within many evolution lines of a rare lineage of Dv that retained sulfate-respiration (SR+) capability, which is not required for metabolic cross-feeding. An in-depth investigation revealed that synergistic epistasis across pairings of Dv and Mm genotypes had enhanced cooperativity within SR− and SR+ assemblages, enabling their coexistence within the same community. Thus, our findings demonstrate that cooperativity of a mutualism can improve through synergistic epistasis between genomes of the interacting species, enabling the coexistence of mutualistic assemblages of generalists and their specialized variants.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle ItemCustom R and Python codes ItemSyntrophy Portal
Turkarslan, Serdar0000-0003-1679-6405
Stopnisek, Nejc0000-0002-1532-6826
Thompson, Anne W.0000-0002-2022-9553
Valenzuela, Jacob J.0000-0002-2320-241X
Wilson, James0000-0001-8503-2041
Hunt, Kristopher A.0000-0003-0024-4913
López García de Lomana, Adrián0000-0002-9748-347X
Lim, Sujung0000-0001-6040-729X
Zhou, Jizhong0000-0003-2014-0564
Hillesland, Kristina L.0000-0002-8779-7926
Baliga, Nitin S.0000-0001-9157-5974
Additional Information:© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Received: 26 July 2020 / Revised: 18 December 2020 / Accepted: 29 January 2021. This material by Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) (, a Science Focus Area Program at Lawrence Berkeley National Laboratory is based upon work supported by the US Department of Energy, Office of Science, Office of Biological, and Environmental Research under contract number DE-AC02-05CH11231. Sequencing of ancestral and early generation cocultures was supported by the National Science Foundation grant no. DEB-1453205 and DEB-1257525 to KLH. Development of the sequencing analysis pipeline was funded by the National Institute of Health under grant number R01AI141953 to NSB. Authors thank to Nicholas Elliott for his help with growth analysis, and Joseph Hellerstein for discussion on data analysis. These authors contributed equally: Serdar Turkarslan, Nejc Stopnisek. Data availability. All sequencing data are available in NCBI Bioproject database (accession number: PRJNA248017). Code availability. Custom R and Python codes are available on GitHub ( Annotated mutations within the context of other functional and regulatory genome information can be explored through Syntrophy Portal ( The authors declare no competing interests.
Funding AgencyGrant Number
Department of Energy (DOE)DE-AC02-05CH11231
Issue or Number:8
PubMed Central ID:PMC8319347
Record Number:CaltechAUTHORS:20210222-100904202
Persistent URL:
Official Citation:Turkarslan, S., Stopnisek, N., Thompson, A.W. et al. Synergistic epistasis enhances the co-operativity of mutualistic interspecies interactions. ISME J 15, 2233–2247 (2021).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108143
Deposited By: George Porter
Deposited On:22 Feb 2021 20:09
Last Modified:04 Aug 2021 19:32

Repository Staff Only: item control page