collaborateurs

Pascale Gerbault

Maître-assistant(e) chez Anthropologie & Immunogénétique

  • T: +41 22 379 69 64
  • office 4-414 (Sciences II)

  • Evidence for Pathogen-Driven Selection Acting on in Response to Malaria in West Africa. Ecol Evol 2025 Feb;15(2):e70933. PMC11850448. 10.1002/ece3.70933. ECE370933.

    résumé

    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 () class II genes (, , and ), 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 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 class II genes, which is consistent with molecular comparisons between genes and their orthologs in chimpanzees (). However, the most striking observation comes from linear modeling, demonstrating that the prevalence of , the primary pathogen of malaria in Africa, significantly explains a large proportion of the nucleotide diversity observed at the gene. , 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 variation in Africa. Additionally, two low-frequency alleles, and also show significant associations with prevalence, supporting resistance to malaria is determined by multigenic and/or multiallelic combinations rather than single allele effects.

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  • Evidence for Pathogen-Driven Selection Acting on HLA-DPB1 in Response to Plasmodium falciparum Malaria in West Africa Ecology and Evolution, 15: e70933. https://doi.org/10.1002/ece3.70933

    résumé

    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.

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  • A genomic history of Aboriginal Australia. Nature 2016 Oct;538(7624):207-214. nature18299. 10.1038/nature18299.

    résumé

    The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10-32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama-Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.

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  • Correction to: "Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection". Evol. Bioinform. Online 2015 ;11(Suppl 2):69. 10.4137/EBO.S39777. ebo-suppl.2-2015-069. PMC4939849.

    résumé

    [This corrects the article DOI: 10.4137/EBO.S33488.].

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  • Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection. Evol. Bioinform. Online 2015 ;11(Suppl 2):27-39. 10.4137/EBO.S33488. ebo-suppl.2-2015-027. PMC4768942.

    résumé

    SELECTOR is a software package for studying the evolution of multiallelic genes under balancing or positive selection while simulating complex evolutionary scenarios that integrate demographic growth and migration in a spatially explicit population framework. Parameters can be varied both in space and time to account for geographical, environmental, and cultural heterogeneity. SELECTOR can be used within an approximate Bayesian computation estimation framework. We first describe the principles of SELECTOR and validate the algorithms by comparing its outputs for simple models with theoretical expectations. Then, we show how it can be used to investigate genetic differentiation of loci under balancing selection in interconnected demes with spatially heterogeneous gene flow. We identify situations in which balancing selection reduces genetic differentiation between population groups compared with neutrality and explain conflicting outcomes observed for human leukocyte antigen loci. These results and three previously published applications demonstrate that SELECTOR is efficient and robust for building insight into human settlement history and evolution.

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  • Evolution of lactase persistence: an example of human niche construction. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2011 Mar;366(1566):863-77. 366/1566/863. 10.1098/rstb.2010.0268. PMC3048992.

    résumé

    Niche construction is the process by which organisms construct important components of their local environment in ways that introduce novel selection pressures. Lactase persistence is one of the clearest examples of niche construction in humans. Lactase is the enzyme responsible for the digestion of the milk sugar lactose and its production decreases after the weaning phase in most mammals, including most humans. Some humans, however, continue to produce lactase throughout adulthood, a trait known as lactase persistence. In European populations, a single mutation (-13910*T) explains the distribution of the phenotype, whereas several mutations are associated with it in Africa and the Middle East. Current estimates for the age of lactase persistence-associated alleles bracket those for the origins of animal domestication and the culturally transmitted practice of dairying. We report new data on the distribution of -13910*T and summarize genetic studies on the diversity of lactase persistence worldwide. We review relevant archaeological data and describe three simulation studies that have shed light on the evolution of this trait in Europe. These studies illustrate how genetic and archaeological information can be integrated to bring new insights to the origins and spread of lactase persistence. Finally, we discuss possible improvements to these models.

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  • Impact of selection and demography on the diffusion of lactase persistence. PLoS ONE 2009 ;4(7):e6369. 10.1371/journal.pone.0006369. PMC2711333.

    résumé

    The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches.

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Mes principaux thèmes de recherche portent sur l'évolution de la diversité génétique dans les populations. J'utilise plus particulièrement des outils bioinformatiques et des modèles de simulation informatique afin d'intégrer différents types de données (par exemple données génétiques et archéologiques) dans l'inférence d'hypothèses évolutives. 

Mes travaux en cours portent sur la diversité de gènes HLA dans des populations africaines avec la Prof. Alicia Sanchez-Mazas (HLA-AFRICA).

Mes intérêts de recherche portent aussi sur les maladies infectieuses, et je co-supervise un projet de doctorat sur la distribution des tréponématoses (la syphilis et le pian) au Ghana (financement GCRF).