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Trajectories for the evolution of bacterial CO₂-concentrating mechanisms

Flamholz, Avi I. and Dugan, Eli and Panich, Justin and Desmarais, John J. and Oltrogge, Luke M. and Fischer, Woodward W. and Singer, Steven W. and Savage, David F. (2022) Trajectories for the evolution of bacterial CO₂-concentrating mechanisms. . (Unpublished)

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Cyanobacteria rely on CO₂ concentrating mechanisms (CCMs) that depend on ≈15 genes to produce two protein complexes: an inorganic carbon (Ci) transporter and a 100+ nm carboxysome compartment that encapsulates rubisco with a carbonic anhydrase (CA) enzyme. Mutations disrupting CCM components prohibit growth in today’s atmosphere (0.04% CO₂), indicating that CCMs evolved to cope with declining environmental CO₂. Indeed, geochemical data and models indicate that atmospheric CO₂ has been generally decreasing from high concentrations over the last ≈3.5 billion years. We used a synthetic reconstitution of a bacterial CCM in E. coli to study the co-evolution of CCMs with atmospheric CO₂. We constructed strains expressing putative ancestors of modern CCMs — strains lacking one or more CCM components — and evaluated their growth in a variety of CO₂ concentrations. Partial forms expressing CA or Ci uptake genes grew better than controls in intermediate CO₂ levels (≈1%); we observed similar phenotypes in genetic studies of two autotrophic bacteria, H. neapolitanus and C. necator. To explain how partial CCMs improve growth, we advance a model of co-limitation of autotrophic growth by CO₂ and HCO₃⁻, as both are required to produce biomass. Our model and results delineated a viable trajectory for bacterial CCM evolution where decreasing atmospheric CO₂ induces an HCO₃⁻ deficiency that is alleviated by acquisition of CAs or Ci uptake genes, thereby enabling the emergence of a modern CCM. This work underscores the importance of considering physiology and environmental context when studying the evolution of biological complexity.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper ItemCode ItemJournal Article
Flamholz, Avi I.0000-0002-9278-5479
Dugan, Eli0000-0003-2400-5511
Desmarais, John J.0000-0002-7739-2079
Oltrogge, Luke M.0000-0001-5716-9980
Fischer, Woodward W.0000-0002-8836-3054
Singer, Steven W.0000-0002-4229-8314
Savage, David F.0000-0003-0042-2257
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. We dedicate this paper to the memory of Danny Salah Tawfik (z”l), a luminary to the scientific community and a dear friend and mentor to AIF. Danny’s many studies of enzyme evolution taught us that evolutionary timescales are accessible in carefully-designed lab-scale experiments and his active cultivation of relationships that transcend generational, professional and cultural divides continues to inspire. We are also indebted to Arren Bar-Even (z”l) for formative conversations guiding this work. Many thanks to Darcy McRose, Elad Noor, and Renee Wang for extensive comments on the manuscript and to Cecilia Blikstad, Julia Borden, Vahe Galstyan, Josh Goldford, Ron Milo, Robert Nichols, Naiya Phillips, Noam Prywes, and Gabe Salmon for helpful input. This research was supported in part by an NSF Graduate Research Fellowship (to A.I.F), NSF Grant No. PHY-1748958, the Gordon and Betty Moore Foundation Grant No. 2919.02, and the Kavli Foundation (to A.I.F), the US Department of Energy (DE-SC00016240 to D.F.S.) and Royal Dutch Shell (Energy and Biosciences Institute project CW163755 to D.F.S. and S.S.). Competing Interest Statement. D.F.S. is a co-founder of Scribe Therapeutics and a scientific advisory board member of Scribe Therapeutics and Mammoth Biosciences. These companies were not involved in this work in any way.
Funding AgencyGrant Number
NSF Graduate Research FellowshipUNSPECIFIED
Gordon and Betty Moore Foundation2919.02
Kavli FoundationUNSPECIFIED
Department of Energy (DOE)DE-SC00016240
Royal Dutch ShellCW163755
Record Number:CaltechAUTHORS:20220706-965478000
Persistent URL:
Official Citation:Trajectories for the evolution of bacterial CO2-concentrating mechanisms Avi I. Flamholz, Eli Dugan, Justin Panich, John J. Desmarais, Luke M. Oltrogge, Woodward W. Fischer, Steven W. Singer, David F. Savage bioRxiv 2022.06.21.497102; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:115352
Deposited By: George Porter
Deposited On:08 Jul 2022 22:34
Last Modified:06 Jan 2023 17:06

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