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Oh Brother, Where Art Thou? Finding Orthologs in the Twilight and Midnight Zones of Sequence Similarity

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Evolutionary Biology

Abstract

Inferring remote orthologs is a persistent challenge in computational biology. The identification of orthologs is necessary for performing evolutionary analyses, comparative genomics, and genome annotation or for functional predictions and sensible planning of experimental studies. If we miss orthologous relationships due to low sequence conservation, we lose a significant amount of information. Given their fast evolutionary rates, remote orthologs can only be identified on protein level. A pair of proteins that has evolved by speciation and has below 30 % sequence identity can be defined as remote orthologs. Their high sequence divergence prevents their unambiguous recognition as orthologous proteins and does not allow a reliable interpretation of their evolutionary relationship. Thus, many remote orthologs remain hidden to date. In this article, I review current methods for remote orthology inference, highlight existing problems in, and discuss potential solutions for discovering remote orthologs.

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Acknowledgements

I would like to thank Frank Schnorrer and Friedhelm Pfeiffer for critical reading of the manuscript. This work was supported by the Max Planck Society and by the CNRS.

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  1. Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany

    Bianca Hermine Habermann

  2. Aix Marseille Université CNRS, IBDM UMR 7288, Marseille, 13288, France

    Bianca Hermine Habermann

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  1. CNRS, Laboratoire Evolution Biologique et Modélisation, Université d’Aix-Marseille, Marseille, France

    Pierre Pontarotti

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Habermann, B.H. (2016). Oh Brother, Where Art Thou? Finding Orthologs in the Twilight and Midnight Zones of Sequence Similarity. In: Pontarotti, P. (eds) Evolutionary Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-41324-2_22

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