Conservation and variation in human and common chimpanzee CD94 and NKG2 genes.
To assess polymorphism and variation in human and chimpanzee NK complex genes, we determined the coding-region sequences for CD94 and NKG2A, C, D, E, and F from several human (Homo sapiens) donors and common chimpanzees (Pan troglodytes). CD94 is highly conserved, while the NKG2 genes exhibit some polymorphism. For all the genes, alternative mRNA splicing variants were frequent among the clones obtained by RT-PCR. Alternative splicing acts similarly in human and chimpanzee to produce the CD94B variant from the CD94 gene and the NKG2B variant from the NKG2A gene. Whereas single chimpanzee orthologs for CD94, NKG2A, NKG2E, and NKG2F were identified, two chimpanzee paralogs of the human NKG2C gene were defined. The chimpanzee Pt-NKG2CI gene encodes a protein similar to human NKG2C, whereas in the chimpanzee Pt-NKG2CII gene the translation frame changes near the beginning of the carbohydrate recognition domain, causing premature termination. Analysis of a panel of chimpanzee NK cell clones showed that Pt-NKG2CI and Pt-NKG2CII are independently and clonally expressed. Pt-NKG2CI and Pt-NKG2CII are equally diverged from human NKG2C, indicating that they arose by gene duplication subsequent to the divergence of chimpanzee and human ancestors. Genomic DNA from 80 individuals representing six primate species were typed for the presence of CD94 and NKG2. Each species gave distinctive typing patterns, with NKG2A and CD94 being most conserved. Seven different NK complex genotypes within the panel of 48 common chimpanzees were due to differences in Pt-NKG2C and Pt-NKG2D genes.
Shum
Benny P
BP
Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, CA 94305, USA.
Flodin
Laura R
LR
Muir
David G
DG
Rajalingam
Raja
R
Khakoo
Salim I
SI
Cleland
Sophia
S
Guethlein
Lisbeth A
LA
Uhrberg
Markus
M
Parham
Peter
P
D000483:Alleles; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D016384:Consensus Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D002679:Pan troglodytes / Q000235:genetics*; D010802:Phylogeny; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics*; D055607:Receptors, Natural Killer Cell; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C527062:KLRC3 protein, human; C527066:KLRC4 protein, human; C497869:KLRD1 protein, human; C527085:KLRK1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell