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Molecular Evolution of Hemojuvelin and the Repulsive Guidance Molecule Family

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Abstract

Repulsive guidance molecules (RGMs) are found in vertebrates and chordates and are involved in embryonic development and iron homeostasis. Members of this family are GPI-linked membrane proteins that contain an N-terminal signal peptide, a C-terminal propeptide, and a conserved RGD motif. Vertebrates are known to possess three paralogues; RGMA and RGMB (sometimes called Dragon) are expressed in the nervous system and are thought to play various roles in neural development. Hemojuvelin (HJV; also called repulsive guidance molecule c, RGMC) is the third member of this family, and mutations in this gene result in a form of juvenile hemochromatosis (type 2A). Phylogenetic analyses of 55 different RGM family sequences from 21 different species support the existence of a novel gene, found only in fish, which we have labeled RGMD. The pattern of conserved residues in each family identifies new candidates for important functional roles, including ligand binding.

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Acknowledgments

We would like to thank the anonymous reviewers for their valuable comments and helpful suggestions.

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  1. Department of Biology, Chatham University, Woodland Road, Pittsburgh, PA, 15232, USA

    Laura Marie Camus & Lisa A. Lambert

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  1. Laura Marie Camus
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Correspondence to Lisa A. Lambert.

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Camus, L.M., Lambert, L.A. Molecular Evolution of Hemojuvelin and the Repulsive Guidance Molecule Family. J Mol Evol 65, 68–81 (2007). https://doi.org/10.1007/s00239-006-0241-5

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