Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees

Abstract

BackgroundThe highly polymorphic genes of the major histocompatibility complex (MHC) class I are involved in defense against viruses and other intracellular pathogens. Although several studies found reduced MHC class I diversity in bonobos in comparison to the closely related chimpanzee, it is unclear if this lower diversity also influences the functional ability of MHC class I molecules in bonobos. Here, we use a bioinformatic approach to analyze the viral peptide binding ability of all published bonobo MHC class I molecules (n = 58) in comparison to all published chimpanzee MHC class I molecules (n = 161) for the class I loci A, B, C and A-like.ResultsWe examined the peptide binding ability of all 219 different MHC class I molecules to 5,788,712 peptides derived from 1432 different primate viruses and analyzed the percentage of bound peptides and the overlap of the peptide binding repertoires of the two species. We conducted multiple levels of analysis on the “species”-, “population”- and “individual”-level to account for the characterization of MHC variation in a larger number of chimpanzees and their broader geographic distribution. We found a lower percentage of bound peptides in bonobos at the B locus in the “population”-level comparison and at the B and C loci in the “individual”-level comparison. Furthermore, we found evidence of a limited peptide binding repertoire in bonobos by tree-based visualization of functional clustering of MHC molecules, as well as an analysis of peptides bound by both species.ConclusionOur results suggest a reduced MHC class I viral peptide binding ability at the B and C loci in bonobos compared to chimpanzees. The effects of this finding on the immune defense against viruses in wild living bonobos are unclear. However, special caution is needed to prevent introduction and spread of new viruses to bonobos, as their defensive ability to cope with new viruses could be limited compared to chimpanzees.Electronic supplementary materialThe online version of this article (10.1186/s12862-019-1352-0) contains supplementary material, which is available to authorized users.

Flexible mixture model approaches that accommodate footprint size variability for robust detection of balancing selection

“…and NKAIN3, which are related to pathogen defense and sexuality, respectively. Accumulating evidence (de Waal, 1990;Hare et al, 2012;de Groot et al, 2017;Wroblewski et al, 2017;Maibach and Vigilant, 2019) suggests that bonobos host unique features in phenotypes related to these areas, and our results may enhance our understanding of both the genetic basis of their idiosyncrasies and their evolutionary history.…”

“…Furthermore, KLRD1 (CD94) has been shown to play an important role in combating viral infections such as cytomegalovirus (CMV; Cerwenka and Lanier, 2016) and influenza (Bongen et al, 2018) in humans, as well as the mousepox virus in mice (Fang et al, 2011). The involvement in viral defense of KLRD1 presents an especially intriguing case for bonobos, because they have been recently shown to have reduced level of polymorphism in MHC class I genes (Maibach et al, 2017;Wroblewski et al, 2017), and were predicted to have lower ability to bind with viral peptides when compared with chimpanzees (Maibach and Vigilant, 2019). The genes encoding another regulator of MHC class I molecules, the Killer cell Immunoglobin-like Receptors (KIR), were also found to have contracted short haplotypes in bonobos (Rajalingam et al, 2001;Walter, 2014;Wroblewski et al, 2019), and with the lineage III KIR genes serving reduced functions (Wroblewski et al, 2019).…”

Differences in MHC-B diversity and KIR epitopes in two populations of wild chimpanzees

“…In addition, our comparison includes all polymorphic sites and not only the sites involved in the forming of the α 1 domain of the peptide binding groove (Bjorkman et al 1987; Saper et al 1991). In sum, drawing conclusions on the functional ability of the MHC-B exon two sequences of our two sets of chimpanzees is rather difficult and would need additional investigation of the MHC-B exon three sequences, which encodes for the α 2 domain of the antigen binding site and proper MHC molecule functionality analysis like the investigation of the ability of MHC molecules to bind viral peptides using bioinformatic binding prediction tools (Hoof et al 2009; Maibach and Vigilant 2019; Pro et al 2014; van Deutekom et al 2011).…”

“…For example, both the bonobo ( Pan paniscus ) and chimpanzee ( Pan troglodytes ) lack the A2 lineage of MHC-A and exhibit lower diversity in MHC class I introns, which are suggested to be result from a selective event driven by lentivirus exposure some 2 million years ago (Ma), before these congeners speciated (Adams et al 2000; de Groot et al 2000; de Groot et al 2002; Lawlor et al 1995; McAdam et al 1995). There is further evidence of functional differences in MHC-B in bonobos compared to chimpanzees, which are attributed to selective processes and/or a severe bottleneck in ancestral bonobos since the divergence of these two taxa (Maibach and Vigilant 2019; Wroblewski et al 2017). The MHC-B locus is of particular interest because of its role in HIV disease progression in humans (Carrington and O’Brien 2003; Fellay et al 2007; Goulder et al 1996; Kiepiela et al 2004; Matzaraki et al 2017; Naranbhai and Carrington 2017) and simian immunodeficiency virus (SIVcpz) infection in chimpanzees (Wroblewski et al 2015).…”

The Genetic Mechanisms Driving Diversification of the KIR Gene Cluster in Primates

“…The shortest bonobo KIR haplotype consists of only the framework genes (47). The contracted bonobo KIR cluster coincides with a reduced nucleotide variation in their MHC class I repertoire, which might be caused by a bottleneck or pathogen-driven selective sweep after divergence from the chimpanzee's lineage (48)(49)(50)(51). In contrast, a highly variable KIR haplotype content is encountered in the macaque, with 4 to 17 functional KIR genes that mainly map to the telomeric region (Figure 1).…”