Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa
ABSTRACT African populations remain underrepresented in studies of human genetic diversity, despite a growing interest in understanding how they have adapted to the diverse environments they live in. In particular, understanding the genetic basis of immune adaptation to pathogens is of paramount imp...
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Wiley
2025-02-01
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| Series: | Ecology and Evolution |
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| Online Access: | https://doi.org/10.1002/ece3.70933 |
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| author | Thomas Goeury Ndeye Faye Pascale Gerbault Viktor Černý Eric Crubézy Jacques Chiaroni Hacene Brouk Lydie Brunet Maxime Galan Natasja G. deGroot José Manuel Nunes Alicia Sanchez‐Mazas |
| author_facet | Thomas Goeury Ndeye Faye Pascale Gerbault Viktor Černý Eric Crubézy Jacques Chiaroni Hacene Brouk Lydie Brunet Maxime Galan Natasja G. deGroot José Manuel Nunes Alicia Sanchez‐Mazas |
| author_sort | Thomas Goeury |
| collection | DOAJ |
| description | ABSTRACT African populations remain underrepresented in studies of human genetic diversity, despite a growing interest in understanding how they have adapted to the diverse environments they live in. In particular, understanding the genetic basis of immune adaptation to pathogens is of paramount importance in a continent such as Africa, where the burden of infectious diseases is a major public health challenge. In this study, we investigated the molecular variation of four Human Leukocyte Antigens (HLA) class II genes (DRB1, DQA1, DQB1 and DPB1), directly involved in the immune response to parasitic infections, in more than 1000 individuals from 23 populations across North, East, Central and West Africa. By analyzing the HLA molecular diversity of these populations in relation to various geographical, cultural and environmental factors, we identified divergent genetic profiles for several (semi‐)nomadic populations of the Sahel belt as a signature of their unique demography. In addition, we observed significant genetic structuring supporting both substantial geographic and linguistic differentiations within West Africa. Furthermore, neutrality tests suggest balancing selection has been shaping the diversity of these four HLA class II genes, which is consistent with molecular comparisons between HLA genes and their orthologs in chimpanzees (Patr). However, the most striking observation comes from linear modeling, demonstrating that the prevalence of Plasmodium falciparum, the primary pathogen of malaria in Africa, significantly explains a large proportion of the nucleotide diversity observed at the DPB1 gene. DPB1*01:01, a highly frequent allele in Burkinabé populations, is identified as a potential protective allele against malaria, suggesting that strong pathogen‐driven positive selection at this gene has shaped HLA variation in Africa. Additionally, two low‐frequency DRB1 alleles, DRB1*08:06 and DRB1*11:02, also show significant associations with P. falciparum prevalence, supporting resistance to malaria is determined by multigenic and/or multiallelic combinations rather than single allele effects. |
| format | Article |
| id | doaj-art-1bc3efb8e2704791b413406952f06f4f |
| institution | Kabale University |
| issn | 2045-7758 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
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| series | Ecology and Evolution |
| spelling | doaj-art-1bc3efb8e2704791b413406952f06f4f2025-08-20T03:26:04ZengWileyEcology and Evolution2045-77582025-02-01152n/an/a10.1002/ece3.70933Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West AfricaThomas Goeury0Ndeye Faye1Pascale Gerbault2Viktor Černý3Eric Crubézy4Jacques Chiaroni5Hacene Brouk6Lydie Brunet7Maxime Galan8Natasja G. deGroot9José Manuel Nunes10Alicia Sanchez‐Mazas11Laboratory of Anthropology, Genetics and Peopling History (AGP), Department of Genetics and Evolution University of Geneva Geneva SwitzerlandLaboratory of Anthropology, Genetics and Peopling History (AGP), Department of Genetics and Evolution University of Geneva Geneva SwitzerlandLaboratory of Anthropology, Genetics and Peopling History (AGP), Department of Genetics and Evolution University of Geneva Geneva SwitzerlandInstitute of Archaeology of the Academy of Sciences of the Czech Republic Archaeogenetics Laboratory Czech Academy of Sciences Prague Czech RepublicInstitut Universitaire de France UMR5288 CNRS University of Toulouse III Paul Sabatier Toulouse FranceADES UMR 7268 Aix Marseille University, EFS, CNRS Marseille FranceService of Hemobiology and Blood Transfusion University Hospital Center Ibn Rochd of Annaba Faculty of Medicine Badji Mokhtar University of Annaba Annaba AlgeriaLaboratory of Anthropology, Genetics and Peopling History (AGP), Department of Genetics and Evolution University of Geneva Geneva SwitzerlandCBGP UMR 1062 INRAE IRD CIRAD Montpellier SupAgro University of Montpellier Montpellier FranceDepartment of Comparative Genetics and Refinement Biomedical Primate Research Centre (BPRC) Rijswijk the NetherlandsLaboratory of Anthropology, Genetics and Peopling History (AGP), Department of Genetics and Evolution University of Geneva Geneva SwitzerlandLaboratory of Anthropology, Genetics and Peopling History (AGP), Department of Genetics and Evolution University of Geneva Geneva SwitzerlandABSTRACT African populations remain underrepresented in studies of human genetic diversity, despite a growing interest in understanding how they have adapted to the diverse environments they live in. In particular, understanding the genetic basis of immune adaptation to pathogens is of paramount importance in a continent such as Africa, where the burden of infectious diseases is a major public health challenge. In this study, we investigated the molecular variation of four Human Leukocyte Antigens (HLA) class II genes (DRB1, DQA1, DQB1 and DPB1), directly involved in the immune response to parasitic infections, in more than 1000 individuals from 23 populations across North, East, Central and West Africa. By analyzing the HLA molecular diversity of these populations in relation to various geographical, cultural and environmental factors, we identified divergent genetic profiles for several (semi‐)nomadic populations of the Sahel belt as a signature of their unique demography. In addition, we observed significant genetic structuring supporting both substantial geographic and linguistic differentiations within West Africa. Furthermore, neutrality tests suggest balancing selection has been shaping the diversity of these four HLA class II genes, which is consistent with molecular comparisons between HLA genes and their orthologs in chimpanzees (Patr). However, the most striking observation comes from linear modeling, demonstrating that the prevalence of Plasmodium falciparum, the primary pathogen of malaria in Africa, significantly explains a large proportion of the nucleotide diversity observed at the DPB1 gene. DPB1*01:01, a highly frequent allele in Burkinabé populations, is identified as a potential protective allele against malaria, suggesting that strong pathogen‐driven positive selection at this gene has shaped HLA variation in Africa. Additionally, two low‐frequency DRB1 alleles, DRB1*08:06 and DRB1*11:02, also show significant associations with P. falciparum prevalence, supporting resistance to malaria is determined by multigenic and/or multiallelic combinations rather than single allele effects.https://doi.org/10.1002/ece3.70933AfricaHLAhuman molecular diversitymalariapathogen‐driven selectionplasmodium falciparum |
| spellingShingle | Thomas Goeury Ndeye Faye Pascale Gerbault Viktor Černý Eric Crubézy Jacques Chiaroni Hacene Brouk Lydie Brunet Maxime Galan Natasja G. deGroot José Manuel Nunes Alicia Sanchez‐Mazas Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa Ecology and Evolution Africa HLA human molecular diversity malaria pathogen‐driven selection plasmodium falciparum |
| title | Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa |
| title_full | Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa |
| title_fullStr | Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa |
| title_full_unstemmed | Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa |
| title_short | Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa |
| title_sort | evidence for pathogen driven selection acting on hla dpb1 in response to plasmodium falciparum malaria in west africa |
| topic | Africa HLA human molecular diversity malaria pathogen‐driven selection plasmodium falciparum |
| url | https://doi.org/10.1002/ece3.70933 |
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