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Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa.

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Title: Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa.
Authors: Goeury, Thomas1 (AUTHOR), Faye, Ndeye1 (AUTHOR), Gerbault, Pascale1 (AUTHOR), Černý, Viktor2 (AUTHOR), Crubézy, Eric3 (AUTHOR), Chiaroni, Jacques4 (AUTHOR), Brouk, Hacene5 (AUTHOR), Brunet, Lydie1,6 (AUTHOR), Galan, Maxime7 (AUTHOR), de Groot, Natasja G.8 (AUTHOR), Nunes, José Manuel1,9 (AUTHOR), Sanchez‐Mazas, Alicia1,9 (AUTHOR) alicia.sanchez‐mazas@unige.ch
Source: Ecology & Evolution (20457758). Feb2025, Vol. 15 Issue 2, p1-18. 18p.
Subject Terms: *Communicable diseases, *Malaria, Human genetic variation, HLA histocompatibility antigens, Genetic profile, Plasmodium falciparum, Parasitic diseases
Geographic Terms: 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 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. [ABSTRACT FROM AUTHOR]
Copyright of Ecology & Evolution (20457758) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa.
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  Data: <searchLink fieldCode="AR" term="%22Goeury%2C+Thomas%22">Goeury, Thomas</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Faye%2C+Ndeye%22">Faye, Ndeye</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gerbault%2C+Pascale%22">Gerbault, Pascale</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Černý%2C+Viktor%22">Černý, Viktor</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Crubézy%2C+Eric%22">Crubézy, Eric</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chiaroni%2C+Jacques%22">Chiaroni, Jacques</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Brouk%2C+Hacene%22">Brouk, Hacene</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Brunet%2C+Lydie%22">Brunet, Lydie</searchLink><relatesTo>1,6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Galan%2C+Maxime%22">Galan, Maxime</searchLink><relatesTo>7</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22de+Groot%2C+Natasja+G%2E%22">de Groot, Natasja G.</searchLink><relatesTo>8</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nunes%2C+José+Manuel%22">Nunes, José Manuel</searchLink><relatesTo>1,9</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sanchez‐Mazas%2C+Alicia%22">Sanchez‐Mazas, Alicia</searchLink><relatesTo>1,9</relatesTo> (AUTHOR)<i> alicia.sanchez‐mazas@unige.ch</i>
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  Data: <searchLink fieldCode="JN" term="%22Ecology+%26+Evolution+%2820457758%29%22">Ecology & Evolution (20457758)</searchLink>. Feb2025, Vol. 15 Issue 2, p1-18. 18p.
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  Data: *<searchLink fieldCode="DE" term="%22Communicable+diseases%22">Communicable diseases</searchLink><br />*<searchLink fieldCode="DE" term="%22Malaria%22">Malaria</searchLink><br /><searchLink fieldCode="DE" term="%22Human+genetic+variation%22">Human genetic variation</searchLink><br /><searchLink fieldCode="DE" term="%22HLA+histocompatibility+antigens%22">HLA histocompatibility antigens</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+profile%22">Genetic profile</searchLink><br /><searchLink fieldCode="DE" term="%22Plasmodium+falciparum%22">Plasmodium falciparum</searchLink><br /><searchLink fieldCode="DE" term="%22Parasitic+diseases%22">Parasitic diseases</searchLink>
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  Data: <searchLink fieldCode="DE" term="%22Africa%22">Africa</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Ecology & Evolution (20457758) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1002/ece3.70933
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      – Code: eng
        Text: English
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        PageCount: 18
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    Subjects:
      – SubjectFull: Communicable diseases
        Type: general
      – SubjectFull: Malaria
        Type: general
      – SubjectFull: Human genetic variation
        Type: general
      – SubjectFull: HLA histocompatibility antigens
        Type: general
      – SubjectFull: Genetic profile
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      – SubjectFull: Plasmodium falciparum
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      – SubjectFull: Parasitic diseases
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      – SubjectFull: Africa
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      – TitleFull: Evidence for Pathogen‐Driven Selection Acting on HLA‐DPB1 in Response to Plasmodium falciparum Malaria in West Africa.
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              Text: Feb2025
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