Biology Faculty Articles
Title
Taxonomic Hierarchy of HLA Class I Allele Sequences
Document Type
Article
Publication Date
11-1999
Publication Title
Genes and Immunity
Keywords
Evolution, HLA, Phylogenetic, Peptide binding region
ISSN
1466-4879
Volume
1
Issue/No.
2
First Page
120
Last Page
129
Abstract
The markedly high levels of polymorphism present in classical class I loci of the human major histocompatibility complex have been implicated in infectious and immune disease recognition. The large numbers of alleles present at these loci have, however, limited efforts to verify associations between individual alleles and specific diseases. As an approach to reduce allele diversity to hierarchical evolutionarily related groups, we performed phylogenetic analyses of available HLAA, B and C allele complete sequences (n = 216 alleles) using different approaches (maximum parsimony, distance-based minimum evolution and maximum likelihood). Full nucleotide and amino acid sequences were considered as well as abridged sequences from the hypervariable peptide binding region, known to interact in vivo, with HLA presented foreign peptide. The consensus analyses revealed robust clusters of 36 HLA-C alleles concordant for full and PBR sequence analyses. HLA-A alleles (n = 60) assorted into 12 groups based on full nucleotide and amino acid sequence which with few exceptions recapitulated serological groupings, however the patterns were largely discordant with clusters prescribed by PBR sequences. HLA-B which has the most alleles (n = 120) and which unlike HLA-A and -C is thought to be subject to frequent recombinational exchange, showed limited phylogenetic structure consistent with recent selection driven retention of maximum heterozygosity and population diversity. Those allele categories recognized offer an explicit phylogenetic criterion for grouping alleles potentially relevant for epidemiologic associations, for inferring the origin of MHC genome organization, and for comparing functional constraints in peptide presentation of HLA alleles.
Additional Comments
NCI contract #: NO1-CO-56000
NSUWorks Citation
McKenzie, L.; Jill Pecon-Slattery; Mary Carrington; and Stephen J. O'Brien. 1999. "Taxonomic Hierarchy of HLA Class I Allele Sequences." Genes and Immunity 1, (2): 120-129. https://nsuworks.nova.edu/cnso_bio_facarticles/651
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Comments
©1999 Stockton Press