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Research article2015Peer reviewedOpen access

Bovine NK-lysin: Copy number variation and functional diversification

Chen, Junfeng; Huddleston, John; Buckley, Reuben M.; Malig, Maika; Lawhon, Sara D.; Skow, Loren C.; Lee, Mi Ok; Eichler, Evan E.; Andersson, Leif; Womack, James E.

Abstract

NK-lysin is an antimicrobial peptide and effector protein in the host innate immune system. It is coded by a single gene in humans and most other mammalian species. In this study, we provide evidence for the existence of four NK-lysin genes in a repetitive region on cattle chromosome 11. The NK2A, NK2B, and NK2C genes are tandemly arrayed as three copies in similar to 30-35-kb segments, located 41.8 kb upstream of NK1. All four genes are functional, albeit with differential tissue expression. NK1, NK2A, and NK2B exhibited the highest expression in intestine Peyer's patch, whereas NK2C was expressed almost exclusively in lung. The four peptide products were synthesized ex vivo, and their antimicrobial effects against both Gram-positive and Gram-negative bacteria were confirmed with a bacteria-killing assay. Transmission electron microcopy indicated that bovine NK-lysins exhibited their antimicrobial activities by lytic action in the cell membranes. In summary, the single NK-lysin gene in other mammals has expanded to a four-member gene family by tandem duplications in cattle; all four genes are transcribed, and the synthetic peptides corresponding to the core regions are biologically active and likely contribute to innate immunity in ruminants.

Keywords

NK-lysin; antimicrobial peptides; gene family expansion; segmental duplication; copy number polymorphism

Published in

Proceedings of the National Academy of Sciences
2015, Volume: 112, number: 52, pages: E7223-E7229
Publisher: NATL ACAD SCIENCES

    UKÄ Subject classification

    Biological Systematics
    Genetics and Breeding

    Publication identifier

    DOI: https://doi.org/10.1073/pnas.1519374113

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/75444