Independent origin of functional MHC class II genes in humans and New World monkeys.

In previous studies, major histocompatibility complex (MHC) class II DP, DQ, and DR families of genes were characterized in different primate species mostly on the basis of their second exon sequences. Resemblances were found between Old World monkey (OWM) and New World monkey (NWM) genes and were interpreted as being the result of transspecies evolution. Subsequent analysis of intron sequences of catarrhine and platyrrhine DRB genes, however, revealed that the amplifiable genes were not, in fact, orthologous. To test other DRB genes and other families of the class II region Southern blot hybridizations were carried out with tamarin genomic DNA using probes specific for the third exons of the tamarin DQA, DQB, DPB, and DRB genes. The hybridizing bands were extracted from the gel and the third exons of the genes were amplified by PCR, cloned, and sequenced. With two exceptions, all NWM class II genes were found to group separately from the human sequences. Only the sequences of one nonfunctional DQB locus appeared to be more closely related to human genes than to other platyrrhine DQB genes. In the DRB family one gene was found that grouped with sheep and strepsirhine DRB sequences and might represent an old gene lineage. To extend the sequences to the second exon, long PCRs were performed on tamarin genomic DNA. This approach was successful for five of the ten third exon sequences. From these data, we conclude that at least the functional MHC class II genes have expanded independently in catarrhines and platyrrhines.

Alu elements support independent origin of prosimian, platyrrhine, and catarrhine Mhc-DRB genes.

The primate major histocompatibility complex (Mhc) genes fall into two classes and each of the classes into several families. Of the class II families, the DRB family has a long and complex evolutionary history marked by gene turnover, rearrangement, and molecular convergence. Because the history is not easily decipherable from sequences alone, Alu element insertions were used as cladistic markers to support the surmised phylogenetic relationships among the DRB genes. Intron 1 segments of 24 DRB genes from five platyrrhine species and five DRB genes from three prosimian species were amplified by PCR and cloned, and the amplification products were sequenced or PCR-typed for Alu repeats. Three Alu elements were identified in the platyrrhine and four in the prosimian DRB genes. One of the platyrrhine elements (Alu50J) is also found in the Catarrhini, whereas the other two (Alu62Sc, Alu63Sc) are restricted to the New World monkeys. Similarly, the four prosimian elements are found only in this taxon. This distribution of Alu elements is consistent with the phylogeny of the DRB genes as determined from their intron 1 sequences in an earlier and the present study. It contradicts the exon 2-based phylogeny and thus corroborates the conclusion that the evolution of DRB exon 2 sequences is, to some extent, shaped by molecular convergence. Taken together, the data indicate that each of the assemblages of DRB genes in prosimians, platyrrhines, and catarrhines is derived from a separate ancestral gene.

Convergent evolution of major histocompatibility complex molecules in humans and New World monkeys.

In both Old World and New World monkeys Mhc-DRB sequences have been found which resemble human DRB1*03 and DRB3 genes in their second exon. The resemblance is shared sequence motifs and clustering of the genes or the encoded proteins in phylogenetic trees. This similarity could be due to common ancestry, convergence at the molecular level, or chance. To test which of these three explanations applies, we sequenced segments of New World monkey and macaque genes which encompass the entire second exon and large parts of both flanking introns. The test strongly supports the monophyly of New World monkey DRB intron sequences. The phylogenies of introns 1 and 2 from DRB1*03-like and DRB3-like genes are congruent, but both are incongruent with the exon 2-based phylogeny. The matching of intron 1- and intron 2-based phylogenies with each other suggests that reciprocal recombination has not played a major role in exon 2 evolution. Statistical comparisons of exon 2 from different DRB1*03 and DRB3 lineages indicate that it was neither gene conversion (descent), nor chance, but molecular convergence that has shaped their characteristic motifs. The demonstration of convergence in anthropoid Mhc-DRB genes has implications for the classification, age, and mechanism of generation of DRB allelic lineages.