Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-07T23:23:59.877Z Has data issue: false hasContentIssue false
  • English
  • Français

Detecting signatures of past pathogen selection on human HLA loci: are there needles in the haystack?

Published online by Cambridge University Press:  15 August 2017

Bridget S. Penman  and
Sunetra Gupta
Bridget S. Penman*
Affiliation:
School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
Sunetra Gupta
Affiliation:
Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK
*
Author for correspondence: Bridget S. Penman, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Human leucocyte antigens (HLAs) are responsible for the display of peptide fragments for recognition by T-cell receptors. The gene family encoding them is thus integral to human adaptive immunity, and likely to be under strong pathogen selection. Despite this, it has proved difficult to demonstrate specific examples of pathogen–HLA coevolution. Selection from multiple pathogens simultaneously could explain why the evolutionary signatures of particular pathogens on HLAs have proved elusive. Here, we present an individual-based model of HLA evolution in the presence of two mortality-causing pathogens. We demonstrate that it is likely that individual pathogen species causing high mortality have left recognizable signatures on the HLA genomic region, despite more than one pathogen being present. Such signatures are likely to exist at the whole-population level, and involve haplotypic combinations of HLA genes rather than single loci.

Keywords

human leucocyte antigen (HLA)host pathogen coevolutionpathogen selectionhuman evolution
Type
Research Article
Information
Parasitology , Volume 145 , Issue 6 , May 2018 , pp. 731 - 739
Check for updates
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Allison, AC (1954) Protection afforded by sickle-cell trait against subtertian malareal infection. British Medical Journal 1, 290–294.Google Scholar
Apps, R, et al. (2013) Influence of HLA-C expression level on HIV control. Science 340, 87–91.CrossRefGoogle ScholarPubMed
Band, G, et al. (2015) A novel locus of resistance to severe malaria in a region of ancient balancing selection. Nature 526, 253–257.Google Scholar
Borghans, JAM, Beltman, JB and De Boer, RJ (2004) MHC polymorphism under host-pathogen coevolution. Immunogenetics 55, 732–739.CrossRefGoogle ScholarPubMed
Capittini, C, et al. (2012) Possible KIR-driven genetic pressure on the genesis and maintenance of specific HLA-A,B haplotypes as functional genetic blocks. Genes and Immunity 13, 452–457.Google Scholar
Carrillo-Bustamante, P, Kesmir, C and de Boer, RJ (2013) Virus encoded MHC-like Decoys diversify the inhibitory KIR repertoire. PLoS Computational Biology 9, e1003264.CrossRefGoogle ScholarPubMed
Carrillo-Bustamante, P, Kesmir, C and de Boer, RJ (2014) Quantifying the protection of activating and inhibiting NK cell receptors during infection with a CMV-like virus. Frontiers in Immunology 5, 20.Google Scholar
Carrillo-Bustamante, P, Kesmir, C and de Boer, RJ (2015) A coevolutionary arms race between hosts and viruses drives polymorphism and polygenicity of NK cell receptors. Molecular Biology and Evolution 32, 2149–2160.CrossRefGoogle ScholarPubMed
Carrington, M (1999) Recombination within the human MHC. Immunological Reviews 167, 245–256.CrossRefGoogle ScholarPubMed
Chappell, P, et al. (2015) Expression levels of MHC class i molecules are inversely correlated with promiscuity of peptide binding. eLife 4, e05345.Google Scholar
Cotton, LA, et al. (2014) Genotypic and functional impact of HIV-1 adaptation to its host population during the North American Epidemic. PLoS Genetics 10, e1004295.Google Scholar
Cullen, M, et al. (2002) High-resolution patterns of meiotic recombination across the human major histocompatibility complex. American Journal of Human Genetics 71, 759–776.Google Scholar
Dean, M, et al. (1996) Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273, 1856–1862.Google Scholar
De Boer, RJ, et al. (2004) Heterozygote advantage fails to explain the high degree of polymorphism of the MHC. Immunogenetics 55, 725–731.Google Scholar
Doherty, PC and Zinkernagel, RM (1975) Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex. Nature 256, 50–52.Google Scholar
Dunstan, SJ, et al. (2014) Variation at HLA-DRB1 is associated with resistance to enteric fever. Nature Genetics 46, 1333–1336.Google Scholar
Eizaguirre, C, et al. (2012a) Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations. Nature Communications 3, 621.CrossRefGoogle ScholarPubMed
Eizaguirre, C, et al. (2012b) Divergent selection on locally adapted major histocompatibility complex immune genes experimentally proven in the field. Ecology Letters 15, 723–731.CrossRefGoogle ScholarPubMed
Flint, J, Hill, AVS and Bowden, DK (1986) High frequencies of α-thalassaemia are the result of natural selection by malaria. Nature 321, 744–750.Google Scholar
Galvani, AP and Slatkin, M (2003) Evaluating plague and smallpox as historical selective pressures for the CCR5-Δ32 HIV-resistance allele. Proceedings of the National Academy of Sciences of the USA 100, 15276–15279.Google Scholar
Haldane, JBS (1949) Disease and evolution. Ricerca Scientifica (suppl) 19, 68.Google Scholar
Hedrick, PW (2002) Pathogen resistance and genetic variation at MHC loci. Evolution 56, 1902–1908.Google Scholar
Hedrick, PW and Verrelli, BC (2006) ‘Ground truth’ for selection on CCR5-Δ32. Trends in Genetics 22, 293–296.Google Scholar
Hiby, SE, et al. (2004) Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. Journal of Experimental Medicine 200, 957–965.Google Scholar
Hill, AVS (2006) Aspects of genetic susceptibility to human infectious diseases. Annual Review of Genetics 40, 469–486.CrossRefGoogle ScholarPubMed
Hill, AVS, et al. (1991) Common West African HLA antigens are associated with protection from severe malaria. Nature 352, 595–600.CrossRefGoogle ScholarPubMed
Horowitz, A, et al. (2016) Class I HLA haplotypes form two schools that educate NK cells in different ways. Science Immunology 1, eaag1672.CrossRefGoogle Scholar
Huang, Y, et al. (1996) The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nature Medicine 2, 1240–1243.Google Scholar
Hughes, AL and Nei, M (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335, 167–170.CrossRefGoogle Scholar
Hummel, S, et al. (2005) Detection of the CCR5-Δ32 HIV resistance gene in Bronze Age skeletons. Genes and Immunity 6, 371–374.Google Scholar
Imbert-Marcille, B, et al. (2014) A FUT2 gene common polymorphism determines resistance to rotavirus a of the P[8] genotype. Journal of Infectious Diseases 209, 1227–1230.CrossRefGoogle Scholar
Jeffery, KJM, et al. (1999) HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proceedings of the National Academy of Sciences of the USA 96, 3848–3853.Google Scholar
Kaslow, RA, et al. (1996) Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nature Medicine 2, 405–411.CrossRefGoogle ScholarPubMed
Khakoo, SI, et al. (2004) HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305, 872–874.Google Scholar
Kouyos, RD, et al. (2009) The role of epistasis on the evolution of recombination in host–parasite coevolution. Theoretical Population Biology 75, 1–13.CrossRefGoogle ScholarPubMed
Kulkarni, S, et al. (2011) Differential microRNA regulation of HLA-C expression and its association with HIV control. Nature 472, 495–498.CrossRefGoogle ScholarPubMed
Kwiatkowski, DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. American Journal of Human Genetics 77, 171–192.CrossRefGoogle ScholarPubMed
Lederberg, J (1999) J. B. S. Haldane (1949) on infectious disease and evolution. Genetics 153, 1–3.Google Scholar
Lenz, TL (2011) Computational prediction of MHC II-antigen binding supports divergent allele advantage and explains trans-species polymorphism. Evolution 65, 2380–2390.Google Scholar
Lindesmith, L, et al. (2003) Human susceptibility and resistance to Norwalk virus infection. Nature Medicine 9, 548–553.CrossRefGoogle ScholarPubMed
Lindo, J, et al. (2016) A time transect of exomes from a Native American population before and after European contact. Nature Communications 7, 13175.Google Scholar
Liu, R, et al. (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86, 367–377.CrossRefGoogle ScholarPubMed
Martin, MP, et al. (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nature Genetics 31, 429–434.CrossRefGoogle ScholarPubMed
McLaren, PJ and Carrington, M (2015) The impact of host genetic variation on infection with HIV-1. Nature Immunology 16, 577–583.Google Scholar
McLaren, PJ, et al. (2015) Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load. Proceedings of the National Academy of Sciences of the United States of America 112, 14658–14663.Google Scholar
Norman, PJ, et al. (2013) Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. PLoS Genetics 9, e1003938.Google Scholar
Parham, P and Moffett, A (2013) Variable NK cell receptors and their MHC class i ligands in immunity, reproduction and human evolution. Nature Reviews Immunology 13, 133–144.Google Scholar
Parham, P, et al. (1989) Diversity and diversification of HLA-A,B,C alleles. Journal of Immunology 142, 3937–3950.Google Scholar
Payne, R, et al. (2014) Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence. Proceedings of the National Academy of Sciences of the United States of America 111, E5393–E5400.Google Scholar
Penman, BS, et al. (2009) Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean. Proceedings of the National Academy of Sciences of the United States of America 106, 21242–21246.Google Scholar
Penman, BS, et al. (2011) Negative epistasis between α+ thalassaemia and sickle cell trait can explain interpopulation variation in South Asia. Evolution 65, 3625–3632.Google Scholar
Penman, BS, Gupta, S and Buckee, CO (2012) The emergence and maintenance of sickle cell hotspots in the Mediterranean. Infection, Genetics and Evolution 12, 1543–1550.Google Scholar
Penman, BS, et al. (2013) Pathogen selection drives nonoverlapping associations between HLA loci. Proceedings of the National Academy of Sciences of the United States of America 110, 19645–19650.Google Scholar
Penman, BS, et al. (2016) Reproduction, infection and killer-cell immunoglobulin-like receptor haplotype evolution. Immunogenetics 68, 755–764.Google Scholar
Prugnolle, F, et al. (2005) Pathogen-driven selection and worldwide HLA class I diversity. Current Biology 15, 1022–1027.Google Scholar
Sabeti, PC, et al. (2005) The case for selection at CCR5-Delta32. PLoS Biology 3, e378.CrossRefGoogle ScholarPubMed
Seich al Basatena, N, et al. (2011) KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection. PLoS Pathogens 7, e1002270.Google Scholar
Siniscalco, M, et al. (1961) Favism and thalassaemia in Sardinia and their relationship to malaria. Nature 190, 1179–1180.Google Scholar
Takahata, N and Nei, M (1990) Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124, 967–978.CrossRefGoogle ScholarPubMed
The International HIV Controllers Study (2010) The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330, 1551–1557.Google Scholar
Thomas, R, et al. (2009) HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C. Nature Genetics 41, 1290–1294.Google Scholar
Thorven, M, et al. (2005) A homozygous nonsense mutation (428G→A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections. Journal of Virology 79, 15351–15355.Google Scholar
Vita, R, et al. (2015) The immune epitope database (IEDB) 3·0. Nucleic Acids Research 43, D405–D412.Google Scholar
Williams, TN, et al. (2005) Negative epistasis between the malaria-protective effects of alpha+ thalassemia and the sickle cell trait. Nature Genetics 37, 1253–1257.CrossRefGoogle ScholarPubMed
Wroblewski, EE, et al. (2015) Signature patterns of MHC diversity in three Gombe communities of wild chimpanzees reflect fitness in reproduction and immune defense against SIVcpz. PLoS Biology 13, e1002144.Google Scholar
Supplementary material: PDF

Penman and Gupta supplementary material

Figures S1-S6

Download Penman and Gupta supplementary material(PDF)
PDF 404.1 KB