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Protein Science (2004), 13:422-430. Published by Cold Spring Harbor Laboratory Press. Copyright © 2004 The Protein Society
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Phylogenetic and evolutionary analysis of the PLUNC gene family

Colin D. Bingle1, Elizabeth E. LeClair2, Suzanne Havard1, Lynne Bingle1, Paul Gillingham3 and C. Jeremy Craven3

1 Academic Unit of Respiratory Medicine, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, UK
2 DePaul University, Department of Biological Sciences, Chicago, Illinois 60614, USA
3 Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK

(RECEIVED July 25, 2003; FINAL REVISION September 12, 2003; ACCEPTED October 5, 2003)



Abstract

The PLUNC family of human proteins are candidate host defense proteins expressed in the upper airways. The family subdivides into short (SPLUNC) and long (LPLUNC) proteins, which contain domains predicted to be structurally similar to one or both of the domains of bactericidal/permeability-increasing protein (BPI), respectively. In this article we use analysis of the human, mouse, and rat genomes and other sequence data to examine the relationships between the PLUNC family proteins from humans and other species, and between these proteins and members of the BPI family. We show that PLUNC family clusters exist in the mouse and rat, with the most significant diversification in the locus occurring for the short PLUNC family proteins. Clear orthologous relationships are established for the majority of the proteins, and ambiguities are identified. Completion of the prediction of the LPLUNC4 proteins reveals that these proteins contain approximately a 150-residue insertion encoded by an additional exon. This insertion, which is predicted to be largely unstructured, replaces the structure homologous to the 40s hairpin of BPI. We show that the exon encoding this region is anomalously variable in size across the LPLUNC proteins, suggesting that this region is key to functional specificity. We further show that the mouse and human PLUNC family orthologs are evolving rapidly, which supports the hypothesis that these proteins are involved in host defense. Intriguingly, this rapid evolution between the human and mouse sequences is replaced by intense purifying selection in a large portion of the N-terminal domain of LPLUNC4. Our data provide a basis for future functional studies of this novel protein family.

Keywords: PLUNC; BPI; rapid evolution; innate immunity

Abbreviations: at, Arabidopsis thaliana • b, bovine • c, chicken • cg, Crassostrea gigas (pacific oyster) • ci, Ciona intestinalis • t, Trout • cael, Caenorhabditis elegans • ec, Equus caballus (horse) • h, human • m, mouse • r, rat

Reprint requests to: Colin D. Bingle, Academic Unit of Respiratory Medicine, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, S10 2JF, UK; e-mail: c.d.bingle{at}sheffield.ac.uk; fax: 00-44 (0) 114-272-1104; or C. Jeremy Craven, Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK; e-mail: c.j.craven{at}sheffield.ac.uk.; fax: 00-44 (0) 114-272-8697.

Supplemental material: See www.proteinscience.org

Article and publication are at http://www.proteinscience.org/cgi/doi/10.1110/ps.03332704.


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