The common marmoset: a new world primate species with limited Mhc class II variability

Abstract

The common marmoset (Callithrix jacchus) is a New World primate species that is highly susceptible to fatal infections caused by various strains of bacteria. We present here a first step in the molecular characterization of the common marmoset's Mhc class II genes by nucleotide sequence analysis of the polymorphic exon 2 segments. For this study, genetic material was obtained from animals bred in captivity as well as in the wild. The results demonstrate that the common marmoset has, like other primates, apparently functional Mhc-DR and -DQ regions, but the Mhc-DP region has been inactivated. At the -DR and -DQ loci, only a limited number of lineages were detected. On the basis of the number of alleles found, the -DQA and -B loci appear to be oligomorphic, whereas only a moderate degree of polymorphism was observed for two of three Mhc-DRB loci. The contact residues in the peptide-binding site of the Caja-DRB1*03 lineage members are highly conserved, whereas the -DRB*W16 lineage members show more divergence in that respect. The latter locus encodes five oligomorphic lineages whose members are not observed in any other primate species studied, suggesting rapid evolution, as illustrated by frequent exchange of polymorphic motifs. All common marmosets tested were found to share one monomorphic type of Caja-DRB*W12 allele probably encoded by a separate locus. Common marmosets apparently lack haplotype polymorphism because the number of Caja-DRB loci present per haplotype appears to be constant. Despite this, however, an unexpectedly high number of allelic combinations are observed at the haplotypic level, suggesting that Caja-DRB alleles are exchanged frequently between chromosomes by recombination, promoting an optimal distribution of limited Mhc polymorphisms among individuals of a given population. This peculiar genetic make up, in combination with the limited variability of the major histocompatability complex class II repertoire, may contribute to the common marmoset's susceptibility to particular bacterial infections.

Figure 1

Alignment of the Caja-DQA- (1a), -DQB- (1b) and -DRB- (1c) deduced amino acid sequences given in the one-letter code. A dash or an asterisk indicates identity with the consensus or deletion of an amino acid, respectively. Unreported sequences are indicated by an N. Colored boxes highlight motifs shared between the lineages of the -DRB1*03 and DRB*W16 loci. The Caja-DRB*W1201 sequence in this report replaces the one reported by Trtková (20). ^†The Caja-DQB1*2201 amino acid sequence is encoded by two different nucleotide sequences that differ only for one synonymous substitution at position 168 (CCG→CCC).

Figure 2

Distribution of alleles at the Caja-DQA1, -DQB1, -DQB2, -DRB1*03, and DRB*W16 loci in 29 common marmosets. Pairs 9314/9315, 9331/9332, 9333/9334, and 9344/9345 are twins. Animals 439, 458, 471, and 536 are from the Brazilian colony; 439 and 536 were born in the wild. NT, nontested. In the case of -DRB, the alleles have been detected by nucleotide sequence analysis after PCR amplification. This means that some -DRB alleles may not have been amplified and that their presence was not detected. This phenomenon explains the heterogeneity in the number of -DRB alleles as depicted in the last two columns of this table. The presence of Caja-DRB*W1201 also was confirmed by denaturing gradient gel electrophoresis.

Figure 3

Nucleotide sequences of the EYSTS amino acid motif as encoded in different primate species, of the infra-orders Catarrhini (Patr, common chimpanzee; Gogo, gorilla; Mamu, rhesus macaque; and Mane, pig-tailed macaque) and Platyrrhini (Camo, capuchin monkey; Saoe, cotton-top tamarin; and Caja, common marmoset). In addition, the different DNA motifs that are observed at the Caja-DRB*W12 and -DRB*W16 loci are shown. The motifs are depicted in color code and correspond with the alleles listed in Fig. 1c and the phylogenetic tree in Fig. 4.

Figure 4

Phylogenetic tree constructed according to the Neighbor-joining method showing the evolutionary relationships between DRB alleles from New World monkeys. Bootstrap values are indicated. The names of the Caja-DRB alleles are depicted in colors. These correspond to the color code used in Figs. 1c and 3.