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Article

Open Issues for Protein Function Assignment in Haloferax volcanii and Other Halophilic Archaea

1
Computational Biology Group, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany
2
Veterinary Biosciences, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville 3010, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: María José Bonete, Mónica Camacho and Julia Esclapez
Genes 2021, 12(7), 963; https://doi.org/10.3390/genes12070963
Received: 16 May 2021 / Revised: 10 June 2021 / Accepted: 15 June 2021 / Published: 24 June 2021
(This article belongs to the Special Issue Molecular Biology of Extremophiles)
Background: Annotation ambiguities and annotation errors are a general challenge in genomics. While a reliable protein function assignment can be obtained by experimental characterization, this is expensive and time-consuming, and the number of such Gold Standard Proteins (GSP) with experimental support remains very low compared to proteins annotated by sequence homology, usually through automated pipelines. Even a GSP may give a misleading assignment when used as a reference: the homolog may be close enough to support isofunctionality, but the substrate of the GSP is absent from the species being annotated. In such cases, the enzymes cannot be isofunctional. Here, we examined a variety of such issues in halophilic archaea (class Halobacteria), with a strong focus on the model haloarchaeon Haloferax volcanii. Results: Annotated proteins of Hfx. volcanii were identified for which public databases tend to assign a function that is probably incorrect. In some cases, an alternative, probably correct, function can be predicted or inferred from the available evidence, but this has not been adopted by public databases because experimental validation is lacking. In other cases, a probably invalid specific function is predicted by homology, and while there is evidence that this assigned function is unlikely, the true function remains elusive. We listed 50 of those cases, each with detailed background information, so that a conclusion about the most likely biological function can be drawn. For reasons of brevity and comprehension, only the key aspects are listed in the main text, with detailed information being provided in a corresponding section of the Supplementary Materials. Conclusions: Compiling, describing and summarizing these open annotation issues and functional predictions will benefit the scientific community in the general effort to improve the evaluation of protein function assignments and more thoroughly detail them. By highlighting the gaps and likely annotation errors currently in the databases, we hope this study will provide a framework for experimentalists to systematically confirm (or disprove) our function predictions or to uncover yet more unexpected functions. View Full-Text
Keywords: haloarchaea; genome annotation; Gold Standard Protein; Haloferax volcanii; annotation error haloarchaea; genome annotation; Gold Standard Protein; Haloferax volcanii; annotation error
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MDPI and ACS Style

Pfeiffer, F.; Dyall-Smith, M. Open Issues for Protein Function Assignment in Haloferax volcanii and Other Halophilic Archaea. Genes 2021, 12, 963. https://doi.org/10.3390/genes12070963

AMA Style

Pfeiffer F, Dyall-Smith M. Open Issues for Protein Function Assignment in Haloferax volcanii and Other Halophilic Archaea. Genes. 2021; 12(7):963. https://doi.org/10.3390/genes12070963

Chicago/Turabian Style

Pfeiffer, Friedhelm, and Mike Dyall-Smith. 2021. "Open Issues for Protein Function Assignment in Haloferax volcanii and Other Halophilic Archaea" Genes 12, no. 7: 963. https://doi.org/10.3390/genes12070963

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