Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co‐evolution among MHC class I region genes

Abstract

In the frog Xenopus, MHC class I antigen presentation and processing genes (the immunoproteasome LMP2 and LMP7 and the transporter TAP1 and TAP2) seem to be closely linked in a primordial organization. Two distinct lineages of class Ia and LMP7 loci were previously identified, thus strongly suggesting co-evolution among 'class I region' genes. We now show that the Xenopus MHC 'class I region' lies between class II and class III genes and we have isolated two distinct alleles at both the TAP1 and TAP2 loci. The alleles at each locus are remarkably divergent from each other and phylogenetic tree analysis revealed in both cases that they diverged from each other 60-100 million years ago (MYA). For lineage-frequency and linkage analysis, 25 wild-caught X. laevis and 16 X. tropicalis were examined. The two lineages were present in different frequencies for X. laevis and X. tropicalis. Nevertheless, in all cases, the LMP7, TAP1, and TAP2 lineages were found in a set comprising one of the two lineages. Furthermore, like the LMP7 lineages, the TAP lineages were detected in most Xenopus species that diverged from a common ancestor 80-100 MYA, suggesting that the 'class I region' biallelic lineages are under balancing selection.

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

“…5), with divergent sequences ranging from >95% amino acid identity in chickens (26) to as low as 70% identity in Xenopus. In Xenopus, tap2 lineages evolved transspecifically, shared across species that diverged on the order of 80-100 Mya (43).…”

Ancestral Organization of the MHC Revealed in the AmphibianXenopus

“…From our previous work using recombinant X. laevis, we ordered the nonmammalian class I region as class II, TAP/LMP, class I/C4 (6,10). However, as shown in Fig.…”

“…Again, this could either be due to an assembly error in X. tropicalis or alternatively to genomic re-organization that happened during tetraploidization. The frog used for the scaffold assembly was heterozygous for the two class I region lineages that are found in all of the Xenopus species (10,64). We have found that the lineages of class I/PSMB8/TAP1/TAP2 are always found within a set in wild-caught animals (10), suggesting that there is a block in recombination between genes in these lineages, perhaps because of major sequence modifications in noncoding regions, recently shown to be true in medaka (65).…”

“…Probes were made from an EST entry for the partial DM␤ gene (BX845472) by PCR at nucleotide positions 63-331, from a X. laevis cDNA library made from mixture of spleen and intestine mRNA. The C2 probe was made by PCR using primers taken from EST entry (BX853282) corresponding to nucleotide positions 42-462, from a X. laevis cDNA library made from mixture of liver, spleen, and thymus mRNA (10). The PCR amplicons were cloned into the TA cloning vector (Invitrogen Life Technologies) and sequenced.…”

“…In our previous studies of the Xenopus MHC in which we tediously cloned the genes orthologous to those of humans one by one, it was shown that synteny seemed to be stable between the two species separated by 350 million years (6,10). This is in contrast to some other nonmammalian vertebrates in which the MHC genes are scattered over the genome, especially for class II and class III region genes (5,7,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”