Patterns of MHC-G-Like and MHC-B Diversification in New World Monkeys

Abstract

The MHC class I (MHC-I) region in New World monkeys (Platyrrhini) has remained relatively understudied. To evaluate the diversification patterns and transcription behavior of MHC-I in Platyrrhini, we first analyzed public genomic sequences from the MHC-G-like subregion in Saimiri boliviensis, Ateles geoffroyi and Callicebus moloch, and from the MHC-B subregion in Saimiri boliviensis. While S. boliviensis showed multiple copies of both MHC-G-like (10) and –B (15) loci, A. geoffroyi and C. moloch had only three and four MHC-G-like genes, respectively, indicating that not all Platyrrhini species have expanded their MHC-I loci. We then sequenced MHC-G-like and -B cDNAs from nine Platyrrhini species, recovering two to five unique cDNAs per individual for both loci classes. In two Saguinus species, however, no MHC-B cDNAs were found. In phylogenetic trees, MHC-G-like cDNAs formed genus-specific clusters whereas the MHC-B cDNAs grouped by Platyrrhini families, suggesting a more rapid diversification of the former. Furthermore, cDNA sequencing in 12 capuchin monkeys showed that they transcribe at least four MHC-G-like and five MHC-B polymorphic genes, showing haplotypic diversity for gene copy number and signatures of positive natural selection at the peptide binding region. Finally, a quantitative index for MHC:KIR affinity was proposed and tested to predict putative interacting pairs. Altogether, our data indicate that i) MHC-I genes has expanded differentially among Platyrrhini species, ii) Callitrichinae (tamarins and marmosets) MHC-B loci have limited or tissue-specific expression, iii) MHC-G-like genes have diversified more rapidly than MHC-B genes, and iv) the MHC-I diversity is generated mainly by genetic polymorphism and gene copy number variation, likely promoted by natural selection for ligand binding.

MHC class II DRB variability in wild black howler monkeys (Alouatta pigra), an endangered New World primate

“…Another point of relevance is the need to incorporate in future studies other functionally important immune genes, such as MHC class I genes, particularly MHC-B and MHC-G like genes that have shown to be highly polymorphic and that are expressed in several NWM, including some from the Atelidae family (van der Wiel et al, 2013;Lugo and Cadavid, 2015;Cao et al, 2015). Non-MHC immune genes, especially those related to viral resistance like the OAS1 (oligoadenylate synthetase) gene (Acevedo-Whitehouse and Cunningham, 2006;Rios et al, 2007), should also be considered since there have been reports of yellow fever outbreaks in populations of other Alouatta species (De Almeida et al, 2012;Crockett, 1998;Holzmann et al, 2010), that could represent a possible threat to the conservation of A. pigra populations.…”

Comparative genetics of the major histocompatibility complex in humans and nonhuman primates

“…However, in contrast to HLA‐A and ‐B , an expansion of the number of the Mamu‐A and Mamu‐B genes is observed. In common marmosets, the equivalent of the HLA‐B gene, Caja‐B , can be detected but it may be nonfunctional (Lugo & Cadavid, 2015); it is therefore presented in grey colour in the figure. The Caja‐G gene is duplicated on a haplotype and encodes molecules that have taken over the classical antigen presentation function in common marmosets (Lugo & Cadavid, 2015;Watkins et al., 1990;van der Wiel et al., 2013).…”

“…The apparent equivalent of HLA‐B can be detected in NWM and shows differential levels of expansion among different NWM species and a low level or tissue‐specific expression in the family of Callitrichidae (e.g. common marmoset and cotton‐top tamarin) (Lugo & Cadavid, 2015). Most NWM, however, display an expansion and diversification of the HLA‐G ‐like gene (Figure 2a).…”

“…In humans, HLA‐G represents a nonclassical MHC class I molecule with features such as restricted tissue distribution and less polymorphism. The HLA‐G ‐like gene in NWM has been found to encode molecules that seem to have taken over the classical MHC class I antigen presentation function (Lugo & Cadavid, 2015;Watkins et al., 1990;van der Wiel, Otting, de Groot, Doxiadis, & Bontrop, 2013).…”