Biology Faculty Articles

Document Type

Article

Publication Date

8-1-1990

Publication Title

Journal of Experimental Medicine

ISSN

0022-1007

Volume

172

Issue/No.

2

First Page

621

Last Page

630

Abstract

Sequence comparisons of seven distinct MHC class I cDNA clones revealed that feline class I molecules have a remarkable similarity to human HLA genes in their organization of functional domains as well as in the nonrandom partitioning of genetic variability according to the functional constraints ascribed to different regions of the MHC molecule. The distribution of the pattern of sequence polymorphism in the cat as compared with genetic diversity of human and mouse class I genes provides evidence for four coordinate factors that contribute to the origin and sustenance of abundant allele diversity that characterizes the MHC in the species. These include: (a) a gradual accumulation of spontaneous mutational substitution over evolutionary time; (b) selection against mutational divergence in regions of the class I molecule involved in T cell receptor interaction and also in certain regions that interact with common features of antigens; (c) positive selection pressure in favor of persistence of polymorphism and heterozygosity at 57 nucleotide residues that comprise the antigen recognition site; and (d) periodic intragenic (interallelic) and intergenic recombination within the class I genes. We describe a highly conserved 23-bp nucleotide sequence within the coding region of the first α-helix that separates two relatively polymorphic segments located in the α1 domain that may act as a template or "hot spot" for homologous recombination between class I alleles.

Comments

© 1990 Rockefeller University Press

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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