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Evaluating Mineral Lattices as Evolutionary Proxies for Metalloprotein Evolution


Protein coordinated iron-sulfur clusters drive electron flow within metabolic pathways for organisms throughout the tree of life. It is not known how iron-sulfur clusters were first incorporated into proteins. Structural analogies to iron-sulfide minerals present on early Earth, suggest a connection in the evolution of both proteins and minerals. The availability of large protein and mineral crystallographic structure data sets, provides an opportunity to explore co-evolution of proteins and minerals on a large-scale using informatics approaches. However, quantitative comparisons are confounded by the infinite, repeating nature of the mineral lattice, in contrast to metal clusters in proteins, which are finite in size. We address this problem using the Niggli reduction to transform a mineral lattice to a finite, unique structure that when translated reproduces the crystal lattice. Protein and reduced mineral structures were represented as quotient graphs with the edges and nodes corresponding to bonds and atoms, respectively. We developed a graph theory-based method to calculate the maximum common connected edge subgraph (MCCES) between mineral and protein quotient graphs. MCCES can accommodate differences in structural volumes and easily allows additional chemical criteria to be considered when calculating similarity. To account for graph size differences, we use the Tversky similarity index. Using consistent criteria, we found little similarity between putative ancient iron-sulfur protein clusters and iron-sulfur mineral lattices, suggesting these metal sites are not as evolutionarily connected as once thought. We discuss possible evolutionary implications of these findings in addition to suggesting an alternative proxy, mineral surfaces, for better understanding the coevolution of the geosphere and biosphere.

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Data and Software Availability

Source code of comparing two molecular graphs based on their maximum common connected edge subgraph, examples and supporting material are freely available at:


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The authors wish to acknowledge Robert Hazen, Saroj Poudel, Corday Selden, Jennifer Timm, Alexei Tyryshkin and Jan Seiss for useful discussions. The authors would also like to thank the reviewers for critically reading this manuscript and providing exceptional feedback that helped produce a more thorough manuscript. In addition, the authors would like to send their greatest appreciation for the scientists that meticulously collected and deposited mineral and protein structural data into public repositories.


This work was supported by NASA grant 80NSSC18M0093 from the NASA Astrobiology Institute. K.N.M. acknowledges support from the NIH IRACDA Postdoctoral Fellowship Program Grant K12GM093854.

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Correspondence to Kenneth N. McGuinness.

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McGuinness, K.N., Klau, G.W., Morrison, S.M. et al. Evaluating Mineral Lattices as Evolutionary Proxies for Metalloprotein Evolution. Orig Life Evol Biosph 52, 263–275 (2022).

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  • Iron-sulfur clusters
  • Protein evolution
  • Greigite
  • FeS minerals
  • Mineral evolution
  • Ferredoxin
  • Protein-mineral co-evolution