Malaria-driven adaptation of MHC class I in wild bonobo populations

Wroblewski, Emily E.; Guethlein, Lisbeth A.; Anderson, Aaron; Liu, Weimin; Li, Yingying; Heisel, Sara E; Connell, Andrew Jesse; Ndjango, Jean-Bosco N.; Bertolani, Paco; Hart, John; Sanz, Crickette; Morgan, David; Peeters, Martine; Sharp, Paul M.; Hahn, Beatrice H.; Parham, Peter

doi:10.1038/s41467-023-36623-9

Cited by 3 publications

(1 citation statement)

References 67 publications

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“…Most likely, this selection process is driven by pathogens endemic to this area, such as HIV-1/SIV and the malaria parasite "Plasmodium falciparum". There are several lines of evidence suggesting that the MHC region in these three species has experienced selection/adaptation under the forces of these pathogens (2,54,(68)(69)(70)(71).…”

Section: Discussionmentioning

confidence: 99%

The KIR repertoire of a West African chimpanzee population is characterized by limited gene, allele, and haplotype variation

de Groot,

Heijmans,

van der Wiel

et al. 2023

Front. Immunol.

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IntroductionThe killer cell immunoglobulin-like receptors (KIR) play a pivotal role in modulating the NK cell responses, for instance, through interaction with major histocompatibility complex (MHC) class I molecules. Both gene systems map to different chromosomes but co-evolved during evolution. The human KIR gene family is characterized by abundant allelic polymorphism and copy number variation. In contrast, our knowledge of the KIR repertoire in chimpanzees is limited to 39 reported alleles, with no available population data. Only three genomic KIR region configurations have been mapped, and seventeen additional ones were deduced by genotyping.MethodsPreviously, we documented that the chimpanzee MHC class I repertoire has been skewed due to an ancient selective sweep. To understand the depth of the sweep, we set out to determine the full-length KIR transcriptome – in our MHC characterized pedigreed West African chimpanzee cohort – using SMRT sequencing (PacBio). In addition, the genomic organization of 14 KIR haplotypes was characterized by applying a Cas9-mediated enrichment approach in concert with long-read sequencing by Oxford Nanopore Technologies.ResultsIn the cohort, we discovered 35 undescribed and 15 already recorded Patr-KIR alleles, and a novel hybrid KIR gene. Some KIR transcripts are subject to evolutionary conserved alternative splicing events. A detailed insight on the KIR region dynamics (location and order of genes) was obtained, however, only five new KIR region configurations were detected. The population data allowed to investigate the distribution of the MHC-C1 and C2-epitope specificity of the inhibitory lineage III KIR repertoire, and appears to be skewed towards C2.DiscussionAlthough the KIR region is known to evolve fast, as observed in other primate species, our overall conclusion is that the genomic architecture and repertoire in West African chimpanzees exhibit only limited to moderate levels of variation. Hence, the ancient selective sweep that affected the chimpanzee MHC class I region may also have impacted the KIR system.

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Section: Discussionmentioning

confidence: 99%

The KIR repertoire of a West African chimpanzee population is characterized by limited gene, allele, and haplotype variation

de Groot,

Heijmans,

van der Wiel

et al. 2023

Front. Immunol.

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MHC-BDiversity and Signs of Respiratory Illness in Wild, East African Chimpanzees (Pan troglodytes schweinfurthii)

Phillips

2023

Preprint

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Many traits, intrinsic and extrinsic to an organism, contribute to interindividual variation in immunity in wild habitats. The vertebrateMajor Histocompatibility Complex (MHC)includes genes encoding antigen-presenting molecules that are highly variable, and that variation often predicts susceptibility/resistance to and recovery from pathogen infection. I compareMHC-Bvariation at two long-term chimpanzee research sites, Kibale National Park in Uganda and Gombe National Park in Tanzania. Using decades of respiratory health data available for these chimpanzees, I test hypotheses associated with maintenance of diversity atMHCloci, including heterozygote, divergent allele, and rare allele advantage hypotheses, and predictions for unique function ofMHC-Bin great apes. I found, despite confirmation of recent shared ancestry between Kibale and Gombe chimpanzees, including an overlappingMHC-Ballele repertoire and similar MHC-B phenotype compositions, chimpanzees from the two research sites experienced differences in the occurrence of respiratory signs and had different associations ofMHC-Bdiversity with signs of respiratory illness. Kibale chimpanzees with heterozygous genotypes and different peptide-binding supertypes were observed less often with respiratory signs than those homozygous or possessing the same supertypes, but this same association was not observed among Gombe chimpanzees. Gombe chimpanzees with specific MHC-B phenotypes that enable engagement of Natural Killer (NK) cells were observed more often with respiratory signs than chimpanzees with other phenotypes, but this was not observed at Kanyawara. This study emphasizes local adaptation in shaping genetic and phenotypic traits in different infectious disease contexts, even among close genetic relatives of the same subspecies, and highlights utility for continued and simultaneous tracking of host immune genes and specific pathogens in wild species.

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Twenty-year co-evolutionary arms race between meerkat MHC and Tuberculosis

Mueller-Klein,

Risely,

Wilhelm

et al. 2024

Preprint

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Pathogen-mediated balancing selection shapes host ecology and evolution across the tree of life, fueling a co-evolutionary arms race based on frequency-dependent adaptations of hosts and counter-adaptations of pathogens. While rare immune genotypes are predicted to be more resistant to pathogens, evidence for this rare allele-advantage and negative frequency-dependent feedbacks has only been observed in model species or inferred from short-term field observations. Evidence from long-term data and wild populations is missing. Here, we leverage two decades of immune genetic and disease surveillance data from over 1,500 wild meerkats (Suricata suricatta) to reveal co-evolutionary dynamics between the Major Histocompatibility Complex (MHC) and Mycobacterium suricattae, causing tuberculosis (TB). We uncover fluctuating adaptive MHC allelic, functional and haplotypic diversity over time compared with stable neutral genetic diversity. Crucially, we show that meerkats carrying the MHC allele Susu-DRB*13 faced initially higher TB infection probability, with the effect reversing over the course of the study, followed again by an increase in frequency of Susu-DRB*13. Similarly, TB progression first accelerated in meerkats carrying Susu-DRB*13, but decelerated thereafter. Susu-DRB*13 (and its supertype/haplotype) also prolonged survival in individuals with clinical TB. Our results present strong evidence that the rare allele-advantage propels negative frequency-dependent selection in a wild mammal. We discuss meerkats’ social structure as possible reasons for these comparably rapid co-evolutionary dynamics.

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Malaria-driven adaptation of MHC class I in wild bonobo populations

Cited by 3 publications

References 67 publications

The KIR repertoire of a West African chimpanzee population is characterized by limited gene, allele, and haplotype variation

The KIR repertoire of a West African chimpanzee population is characterized by limited gene, allele, and haplotype variation

MHC-BDiversity and Signs of Respiratory Illness in Wild, East African Chimpanzees (Pan troglodytes schweinfurthii)

Twenty-year co-evolutionary arms race between meerkat MHC and Tuberculosis

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