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

Juan S Lugo,Luis F Cadavid,Tzen-Yuh Chiang

doi:10.1371/journal.pone.0131343

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.

Highlights

Major Histocompatibility Complex (MHC) class I molecules present processed peptides to CD8+ T lymphocytes and interact with Natural Killer (NK) cell receptors to modulate immune responses directed against self-altered cells [1]
In order to gain a better understanding of the MHC class I genes in Platyrrhini, we have investigated their diversification processes at three different levels, i) at the genomic level by analyzing the MHC class I gene organization in three Platyrrhini species using public sequence information, ii) at the transcriptomic level by cloning and sequencing MHC-G-like and MHC-B complementary DNA (cDNA) from 10 species representing two Platyrrhini families (Cebidae and Atelidae), and iii) at the gene level by studying the polymorphism of MHC-G-like and MHC-B loci in a population of 12 white-fronted capuchin monkeys (Cebus albifrons)
Sequence database searching using known MHC class I sequences resulted in the identification of bacterial artificial chromosomes (BACs) clone sequences and generation sequencing scaffolds containing unpublished MHC class I genes from the Bolivian squirrel monkey (Saimiri boliviensis), the spider monkey (Ateles geoffroyi), and the dusky titi monkey (Callicebus moloch)

Summary

Introduction

Major Histocompatibility Complex (MHC) class I molecules present processed peptides to CD8+ T lymphocytes and interact with Natural Killer (NK) cell receptors to modulate immune responses directed against self-altered cells [1]. The hallmark of the MHC class I system is the high genetic polymorphism of its loci, which has been promoted by selective pressures from rapidly evolving pathogens to evade immune recognition [2]. There are six functional MHC class I genes, HLA-A, -B. -C, -E, -F, and -G, that, together with 11 MHC class I. The human MHC class I region is divided into three contiguous subgenomic sections, often referred to as the alpha block, located at the telomeric end of the region and containing HLA-F, -G, and -A, the beta block, located at the centromeric end of the region and containing HLA-B and -C, and the kappa block, at the central part of the region, containing HLA-E [5]

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Conclusion