Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals.

Abstract

The class I major histocompatibility complex genes are composed of classical and nonclassical genes, the latter being largely nonfunctional. To understand the evolutionary relationships of the two groups of class I genes, a phylogenetic analysis of DNA sequences was conducted using 45 genes from six mammalian and one avian species. The results indicate that nonclassical genes in one species are more closely related to classical genes from the same species than to nonclassical genes from a species belonging to a different order or family. This indicates that the differentiation of classical and nonclassical genes occurs rather rapidly in the genome. Classical genes are apparently duplicated with a high frequency in the evolutionary process, and many of the duplicated genes seem to degenerate into nonclassical genes as a result of deleterious mutation. The nonclassical Qa genes in the mouse have sequences homologous to regulatory sequences involved in the universal expression of classical class I genes, but they have accumulated numerous nucleotide substitutions in these sequences. The pattern of nucleotide substitution in nonclassical genes is different from that in classical genes. In nonclassical genes, the rate of nonsynonymous substitution is higher in the antigen recognition site than in other gene regions, as is true of classical genes. However, unlike the case of classical genes, the nonsynonymous rate does not always exceed the synonymous rate in the antigen recognition site. Nonclassical proteins further differ from classical proteins in having amino acid replacements in conserved antigen recognition site positions. These observations are consistent with the hypothesis that nonclassical genes have originated from classical genes but have lost classical class I function because of deleterious mutation.

Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates

“…Conservation of gene copies preserving classical features accompanied by seemingly random loss of older non-classical gene duplicates is somewhat reminiscent of MHC class I evolution described for higher vertebrates [45]. However, the mode of the teleost fish MHC class II evolution highly contrasts with that of the tetrapod species in which not only the classical class II but also the non-classical DM genes are highly conserved.…”

Expression and phylogenetic analyses reveal paralogous lineages of putatively classical and non-classical MHC-I genes in three sparrow species (Passer)

“…It is possible that these different sets of paralogous genes are even older and evolved in an ancient common ancestor of galliforms more than 65 million years ago [53]. However, non-classical genes in sparrows of the order Passeriformes and species within the order Galliformes are not likely to be orthologous, presently available data suggest that the non-classical genes originate from more recent duplications of classical genes, a pattern seen also among distantly related mammals [14, 30]. Though, orthologous clusters of classical and non-classical MHC-I genes among relatively closely related mammals has been seen in hominids and here the classical and non-classical genes even cluster by locus [10].…”

“…In mammals, classical MHC-I genes (MHC-Ia) are highly polymorphic and highly expressed, whereas non-classical (MHC-Ib) are less polymorphic and have low expression [12, 13]. The non-classical genes do not appear to have a common origin among distantly related mammals but seem to have arisen independently from recent duplications of classical MHC-I genes within species [14]. MHC-Ia molecules play an important role in adaptive immunity by presenting peptides to T-cells [1], whereas MHC-Ib molecules have other immune functions [12, 13, 15, 16].…”

Evolution of nonclassical MHC-dependent invariant T cells

“…This has been partly attributed to the “birth and death” model of evolution in which new genes arise via gene duplication [26]. While some of these duplicated genes are maintained in the genome others undergo neofunctionalization or degradation [27-28]. To date, phylogenetic relationships among various nonclassical MHC class I genes are not fully understood and only few unambiguous orthologous or even homologous have been described across different vertebrate orders and families.…”