Understanding how deleterious genetic variation is distributed across human populations is of key importance in evolutionary biology and medical genetics. However, the impact of population size changes and gene flow on the corresponding mutational load remains a controversial topic. Here, we report high-coverage exomes from 300 rainforest hunter-gatherers and farmers of central Africa, whose distinct subsistence strategies are expected to have impacted their demographic pasts. Detailed demographic inference indicates that hunter-gatherers and farmers recently experienced population collapses and expansions, respectively, accompanied by increased gene flow. We show that the distribution of deleterious alleles across these populations is compatible with a similar efficacy of selection to remove deleterious variants with additive effects, and predict with simulations that their present-day additive mutation load is almost identical. For recessive mutations, although an increased load is predicted for hunter-gatherers, this increase has probably been partially counteracted by strong gene flow from expanding farmers. Collectively, our predicted and empirical observations suggest that the impact of the recent population decline of African hunter-gatherers on their mutation load has been modest and more restrained than would be expected under a fully recessive model of dominance.

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We thank all the participants for providing the DNA samples used in this study. We thank the Paleogenomics and Molecular Genetics Platform of the Musée de l’Homme-Muséum National d'Histoire Naturelle for technical assistance with DNA sample preparation. We thank G. Laval, L. Excoffier, M. Rotival and S. Ait Kaci Azzou for helpful discussions, and N. Joly for help with computational resources. This work was supported by the Institut Pasteur, Centre National de la Recherche Scientifique and Agence Nationale de la Recherche grant 'AGRHUM' (ANR-14-CE02-0003-01). M.L. was supported by the Fondation pour la Recherche Médicale (FDT20170436932) and A.K. by a Pasteur-Roux fellowship.

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Author notes

  1. These authors contributed equally: Marie Lopez and Athanasios Kousathanas.


  1. Unit of Human Evolutionary Genetics, Institut Pasteur, Paris, France

    • Marie Lopez
    • , Athanasios Kousathanas
    • , Hélène Quach
    • , Christine Harmant
    • , Etienne Patin
    •  & Lluís Quintana-Murci
  2. Centre National de la Recherche Scientifique UMR 2000, Paris, France

    • Marie Lopez
    • , Athanasios Kousathanas
    • , Hélène Quach
    • , Christine Harmant
    • , Etienne Patin
    •  & Lluís Quintana-Murci
  3. Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France

    • Marie Lopez
    • , Athanasios Kousathanas
    • , Hélène Quach
    • , Christine Harmant
    • , Etienne Patin
    •  & Lluís Quintana-Murci
  4. Laboratoire de Langue, Culture et Cognition, Université Omar Bongo, Libreville, Gabon

    • Patrick Mouguiama-Daouda
  5. Centre National de la Recherche Scientifique UMR 5596, Dynamique du Langage, Université Lumière-Lyon 2, Lyon, France

    • Patrick Mouguiama-Daouda
    •  & Jean-Marie Hombert
  6. Institut de Recherche pour le Développement UMR 208, Muséum National d’Histoire Naturelle, Paris, France

    • Alain Froment
  7. Departments of Anthropology and Biology, Pennsylvania State University, University Park, PA, USA

    • George H. Perry
  8. Université de Montréal, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, Canada

    • Luis B. Barreiro
  9. Centre National de la Recherche Scientifique UMR 7206, Muséum National d’Histoire Naturelle, Université Paris Diderot, Sorbonne Paris Cité, Paris, France

    • Paul Verdu


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A.K. and M.L. designed the analytical approach and performed the analyses with input from E.P. and L.Q.-M. H.Q. and C.H. performed the experiments. P.M.-D., J.-M.H., A.F., G.H.P., L.B.B. and P.V. collected the samples. L.Q.-M. conceived the study with input from E.P. and obtained funding. The manuscript was written by A.K., M.L., E.P. and L.Q.-M. with input from all authors.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Athanasios Kousathanas or Lluís Quintana-Murci.

Supplementary information

  1. Supplementary Information

    Supplementary notes, figures, tables (1–9) and references

  2. Life Sciences Reporting Summary

  3. Supplementary Table 10

    Clinically relevant variants identified in the exome of African hunter-gathering and farming populations. List of variants annotated with the highest clinical significance in ClinVar database and their frequencies in each of the examined populations

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