Remarkable Conservation of Distinct Nonclassical MHC Class I Lineages in Divergent Amphibian Species

Abstract

Nonclassical MHC class Ib (class Ib) genes are heterogeneous genes encoding molecules that are structurally similar to classical MHC class Ia molecules but with limited tissue distribution and polymorphism. Mammalian class Ib genes have diverse and often uncharacterized functions, and because of their rapid rate of evolution, class Ib phylogeny is difficult to establish. We have conducted an extensive genomic, molecular, and phylogenetic characterization of class Ib genes in two Xenopodinae amphibian species of different genera that diverged from a common ancestor as long ago as primates and rodents (~65 million years). In contrast with the unsteadiness of mammalian class Ib genes, our results reveal an unusual degree of conservation of most Xenopodinae class Ib gene lineages, including a novel monogenic lineage represented by the divergent Xenopus laevis XNC10 gene and its unequivocal Silurana (Xenopus) tropicalis orthologue, SNC10. The preferential expression of this gene lineage by thymocytes themselves from the onset of thymic organogenesis is consistent with a specialized role of class Ib in early T cell development and suggests such a function is conserved in all tetrapods.

Nonclassical MHC class I-dependent invariant T cells are evolutionarily conserved and prominent from early development in amphibians

“…There are several observations that support the idea of a conserved antigen. First, XNC10 has a unique putative peptide binding domain distinct from all other X. laevis class Ib as well as class Ia genes (15). The putative peptide-docking residues of XNC10 are highly conserved with those identified from the X. tropicalis homolog SNC10, especially in the C terminus, suggesting that XNC10 presents common or conserved (either endogenous or exogenous) antigenic motif.…”

“…The putative peptide-docking residues of XNC10 are highly conserved with those identified from the X. tropicalis homolog SNC10, especially in the C terminus, suggesting that XNC10 presents common or conserved (either endogenous or exogenous) antigenic motif. In this context, it is interesting to note that, based on Southern blot cross-hybridization, the XNC10 gene seems to be conserved and diploidized in all species of the Xenopodinae subfamily, regardless of their ploidy (diploid to dodecaploid) (15). Second, although the direct interaction between XNC10 and the invariant TCR expressed on iVα6T cells has not yet been shown, it represents a likely target.…”

“…XNC10 represents a unique class Ib monogenic lineage phylogenetically distinct from both X. laevis class Ia and other XNC genes but highly conserved among divergent Xenopus species and characterized by interspecies sequence conservation in its putative antigen binding domain (15). Additionally, the XNC10 gene is preferentially expressed by thymocytes as early as 3 d postfertilization (14).…”

“…Conversely, certain class Ib genes are expressed in tadpoles at the onset of thymic organogenesis (14). This expression pattern and the unusually high conservation of certain Xenopus class Ib genes (15) have prompted us to determine whether these class Ib molecules are involved in amphibian iT cell development.…”

“…The Xenopus nonclassical gene (XNC) class Ib gene XNC10 is one of X. laevis 30 XNC genes (14)(15)(16). XNC10 represents a unique class Ib monogenic lineage phylogenetically distinct from both X. laevis class Ia and other XNC genes but highly conserved among divergent Xenopus species and characterized by interspecies sequence conservation in its putative antigen binding domain (15).…”