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Functional Annotations of Paralogs: A Blessing and a Curse

Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA
Author to whom correspondence should be addressed.
Academic Editor: Niles Lehman
Received: 1 July 2016 / Revised: 29 August 2016 / Accepted: 2 September 2016 / Published: 8 September 2016
(This article belongs to the Section Life Sciences)
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Gene duplication followed by mutation is a classic mechanism of neofunctionalization, producing gene families with functional diversity. In some cases, a single point mutation is sufficient to change the substrate specificity and/or the chemistry performed by an enzyme, making it difficult to accurately separate enzymes with identical functions from homologs with different functions. Because sequence similarity is often used as a basis for assigning functional annotations to genes, non-isofunctional gene families pose a great challenge for genome annotation pipelines. Here we describe how integrating evolutionary and functional information such as genome context, phylogeny, metabolic reconstruction and signature motifs may be required to correctly annotate multifunctional families. These integrative analyses can also lead to the discovery of novel gene functions, as hints from specific subgroups can guide the functional characterization of other members of the family. We demonstrate how careful manual curation processes using comparative genomics can disambiguate subgroups within large multifunctional families and discover their functions. We present the COG0720 protein family as a case study. We also discuss strategies to automate this process to improve the accuracy of genome functional annotation pipelines. View Full-Text
Keywords: paralog; ortholog; homolog; annotation; genome context; phylogeny; signature motif; genome; multigene families paralog; ortholog; homolog; annotation; genome context; phylogeny; signature motif; genome; multigene families

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Zallot, R.; Harrison, K.J.; Kolaczkowski, B.; de Crécy-Lagard, V. Functional Annotations of Paralogs: A Blessing and a Curse. Life 2016, 6, 39.

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