Comparative genomic analysis of mammalian NKG2D ligand family genes provides insights into their origin and evolution

NKG2D is a major activating receptor of natural killer cells. Its ligands are major histocompatibility complex (MHC) class I-like molecules whose expression is induced by cellular stresses such as infections and tumorigenesis. Humans have two families of NKG2D ligands (NKG2DL): MHC class I-related c...

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Bibliographic Details
Published in:Immunogenetics (New York) 2010-07, Vol.62 (7), p.441-450
Main Authors: Kondo, Mizuho, Maruoka, Takako, Otsuka, Noriyuki, Kasamatsu, Jun, Fugo, Kazunori, Hanzawa, Naoto, Kasahara, Masanori
Format: Article
Language:English
Subjects:
Activating ligands
Allergology
Amino Acid Sequence
Animals
Biomedical and Life Sciences
Biomedicine
Cattle
Cell Biology
Computational Biology
Evolution, Molecular
Gene Function
Genome
GPI-Linked Proteins
Growth Differentiation Factor 15 - genetics
Histocompatibility Antigens Class I - genetics
Human Genetics
Humans
Immunology
Intracellular Signaling Peptides and Proteins - genetics
Ligands
Mammals - genetics
Membrane Glycoproteins - genetics
Membrane Proteins - genetics
MIC
Mice
MILL
Molecular Sequence Data
NK Cell Lectin-Like Receptor Subfamily D - genetics
opossums
Opossums - genetics
Original Paper
Phylogeny
RAET
Rats
ULBP
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Summary:NKG2D is a major activating receptor of natural killer cells. Its ligands are major histocompatibility complex (MHC) class I-like molecules whose expression is induced by cellular stresses such as infections and tumorigenesis. Humans have two families of NKG2D ligands (NKG2DL): MHC class I-related chains (MIC) encoded in the MHC and UL16-binding proteins (ULBP) encoded outside the MHC. By contrast, mice have only the latter family of ligands; instead, they have non-MHC-encoded MILL molecules that are closely related to MIC, but do not function as NKG2DL. To gain insights into the origin and evolution of MIC, ULBP, and MILL gene families, we conducted comparative genomic analysis of NKG2DL family genes in five mammalian species. In the opossum MHC, we identified a ULBP-like gene adjacent to a previously described MIC-like gene, suggesting that ULBP genes were originally encoded in the MHC. The opossum genome also contained a transcribed MILL-like gene in a region syntenic to the rodent regions encoding MILL molecules. These observations indicate that MIC-, ULBP-, and MILL-like genes emerged before the divergence of placental and marsupial mammals. Comparison of the human, cattle, rat, mouse, and opossum genomes indicates that after emigration from the MHC, ULBP genes underwent extensive duplications in each species. In mice, some of the ULBP genes appear to have been translocated telomerically on the same chromosome, forming a major cluster of existent NKG2DL genes.
ISSN:0093-7711
1432-1211
DOI:10.1007/s00251-010-0438-z