Characterization of MHC cDNA clones in the domestic cat. Diversity and evolution of class I genes.

Abstract

The abundant functional polymorphism and evolutionary divergence of mammalian MHC class I genes has been affirmed recently by sequence analysis of more than 40 mouse H-2 and human HLA transcripts. In a comparative approach to the evolution of the MHC, we isolated eight molecular clones of feline MHC (termed FLA for feline leukocyte antigen) class I genes from a cDNA library of a cat T cell lymphoma line. DNA sequence analysis of eight clones revealed that they all fell into one of two internally identical allelic groups which differed by 9% of their nucleotide sequences. The occurrence of only two allelic cDNA clones is consistent with the expression of a single heterozygous functional class I gene in the studied cell line despite the occurrence of more than 20 class I copies estimated to be present in the cat genome. Comparison of the FLA class I coding sequence with other class I genes from other species revealed that the domestic cat genes display 81 to 82% sequence identity with human, and 73 to 79% sequence identity with mouse class I genes. Feline and human class I genes have similar sequences and protein structures, with three (alpha) extracellular domains, one transmembrane domain, and one cytoplasmic domain. Variable codons detected in FLA class I alleles were, in most cases, in positions which were also variable in humans and mice, whereas invariant positions with defined functional constraints were generally conserved and invariant between the three species as well. Southern analysis of DNA from diverse species of Felidae revealed a similar numerosity and restriction pattern indicating conservation of the organization of class I genes during the Felidae radiation.