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Dairying, diseases and the evolution of lactase persistence in Europe

  • Richard P. Evershed*
  • , George Davey Smith*
  • , Mélanie Roffet-Salque*
  • , Adrian Timpson
  • , Yoan Diekmann
  • , Matthew S. Lyon
  • , Lucy J. E. Cramp
  • , Emmanuelle Casanova
  • , Jessica Smyth
  • , Helen L. Whelton
  • , Julie Dunne
  • , Veronika Brychova
  • , Lucija Šoberl
  • , Pascale Gerbault
  • , Rosalind E. Gillis
  • , Volker Heyd
  • , Emily Johnson
  • , Iain Kendall
  • , Katie Manning
  • , Arkadiusz Marciniak
  • Alan K. Outram, Jean-Denis Vigne, Stephen Shennan, Andrew Bevan, Sue Colledge, Lyndsay Allason-Jones, Luc Amkreutz, Alexandra Anders, Rose-Marie Arbogast, Adrian Bălăşescu, Eszter Bánffy, Alistair Barclay, Anja Behrens, Peter Bogucki, Ángel Carrancho Alonso, José Miguel Carretero, Nigel Cavanagh, Erich Claßen, Hipolito Collado Giraldo, Matthias Conrad, Piroska Csengeri, Lech Czerniak, Maciej Dębiec, Anthony Denaire, László Domboróczki, Christina Donald, Julia Ebert, Christopher Evans, Marta Francés-Negro, Detlef Gronenborn, Fabian Haack, Matthias Halle, Caroline Hamon, Roman Hülshoff, Michael Ilett, Eneko Iriarte, János Jakucs, Christian Jeunesse, Melanie Johnson, Andy M. Jones, Necmi Karul, Dmytro Kiosak, Nadezhda Kotova, Rüdiger Krause, Saskia Kretschmer, Marta Krüger, Philippe Lefranc, Olivia Lelong, Eva Lenneis, Andrey Logvin, Friedrich Lüth, Tibor Marton, Jane Marley, Richard Mortimer, Luiz Oosterbeek, Krisztián Oross, Juraj Pavúk, Joachim Pechtl, Pierre Pétrequin, Joshua Pollard, Richard Pollard, Dominic Powlesland, Joanna Pyzel, Pál Raczky, Andrew Richardson, Peter Rowe, Stephen Rowland, Ian Rowlandson, Thomas Saile, Katalin Sebők, Wolfram Schier, Germo Schmalfuß, Svetlana Sharapova, Helen Sharp, Alison Sheridan, Irina Shevnina, Iwona Sobkowiak-Tabaka, Peter Stadler, Harald Stäuble, Astrid Stobbe, Darko Stojanovski, Nenad Tasić, Ivo van Wijk, Ivana Vostrovská, Jasna Vuković, Sabine Wolfram, Andrea Zeeb-Lanz, Mark G. Thomas*
*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

144 Citations (Scopus)
614 Downloads (Pure)

Abstract

In European and many African, Middle Eastern and Southern Asian populations lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the last 10,000 years. While LP selection and prehistoric milk consumption must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions. We provide detailed distributions of milk exploitation across Europe over the last 9k years using c. 7,000 pottery fat residues from >550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Surprisingly, comparison of model likelihoods indicates that LP selection varying with levels of prehistoric milk exploitation provides no better explanation of LP allele frequency trajectories than uniform selection since the Neolithic. In the UK Biobank cohort of ~500K contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests other hypotheses on the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available, but that under particular conditions and microbiological milieux this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation – proxies for these drivers – provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.
Original languageEnglish
Article number608
Pages (from-to)336-345
Number of pages10
JournalNature
Volume608
Issue number7922
Early online date27 Jul 2022
DOIs
Publication statusPublished - 11 Aug 2022

Bibliographical note

Funding Information:
This study was funded by the European Research Council (ERC) Advanced Grant ‘NeoMilk’ FP7-IDEAS-ERC/324202. M.R.-S. thanks the Royal Society for funding her Dorothy Hodgkin Fellowship (DHF\R1\180064 and RGF\EA\181067). The Natural Environment Research Council (NERC) are thanked for partial funding of the National Environmental Isotope Facility (NEIF; NE/V003917/1). We wish to thank the NERC (NE/V003917/1), the ERC (FP7-IDEAS-ERC/340923) and the University of Bristol for funding GC–MS and GC–IRMS capabilities used for this work. Y.D. and M.G.T. received funding from the ERC Horizon 2020 research and innovation programme (grant agreement no. 788616 YMPACT) and A.T. and M.G.T. received funding from the ERC Horizon 2020 research and innovation programme (grant agreement no. 951385 COREX). G.D.S. and M.S.L. work in the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/1). P. Bickle (University of York, UK) and D. Altoft are acknowledged for the sampling of some potsherds from this study. We thank S. Kalieva and V. Logvin (Kostanay State University, Kazakhstan), C. Lohr (Leibniz Research Institute for Archaeology, Mainz, Germany), J. Lüning (Johann Wolfgang Goethe-Universität, Frankfurt, Germany), I. Pavlů (Institute of Archaeology of the Academy of Sciences of the Czech Republic) and R. W. Schmitz (LVR-LandesMuseum, Bonn, Germany) for providing some of the sherds presented in this study. We are grateful to K. Dwyer, teaching fellow in English grammar and research methodology at University College London (UCL), for clarifying lactase non-persistence as the correct usage over non-lactase persistence, on the basis that ‘non’ qualifies persistence, even if lactase persistence is considered a compound noun. We are also grateful to L. Howe, Senior Research Associate at the MRC IEU for providing derived spousal pairs in UK Biobank. We acknowledge the use of the UCL Computer Science ECON High-Performance Computing (HPC) Cluster (ECON@UCL) and associated support services, in the completion of this work. This study was also supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Funding Information:
This study was funded by the European Research Council (ERC) Advanced Grant ‘NeoMilk’ FP7-IDEAS-ERC/324202. M.R.-S. thanks the Royal Society for funding her Dorothy Hodgkin Fellowship (DHF\R1\180064 and RGF\EA\181067). The Natural Environment Research Council (NERC) are thanked for partial funding of the National Environmental Isotope Facility (NEIF; NE/V003917/1). We wish to thank the NERC (NE/V003917/1), the ERC (FP7-IDEAS-ERC/340923) and the University of Bristol for funding GC–MS and GC–IRMS capabilities used for this work. Y.D. and M.G.T. received funding from the ERC Horizon 2020 research and innovation programme (grant agreement no. 788616 YMPACT) and A.T. and M.G.T. received funding from the ERC Horizon 2020 research and innovation programme (grant agreement no. 951385 COREX). G.D.S. and M.S.L. work in the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/1). P. Bickle (University of York, UK) and D. Altoft are acknowledged for the sampling of some potsherds from this study. We thank S. Kalieva and V. Logvin (Kostanay State University, Kazakhstan), C. Lohr (Leibniz Research Institute for Archaeology, Mainz, Germany), J. Lüning (Johann Wolfgang Goethe-Universität, Frankfurt, Germany), I. Pavlů (Institute of Archaeology of the Academy of Sciences of the Czech Republic) and R. W. Schmitz (LVR-LandesMuseum, Bonn, Germany) for providing some of the sherds presented in this study. We are grateful to K. Dwyer, teaching fellow in English grammar and research methodology at University College London (UCL), for clarifying lactase non-persistence as the correct usage over non-lactase persistence, on the basis that ‘non’ qualifies persistence, even if lactase persistence is considered a compound noun. We are also grateful to L. Howe, Senior Research Associate at the MRC IEU for providing derived spousal pairs in UK Biobank. We acknowledge the use of the UCL Computer Science ECON High-Performance Computing (HPC) Cluster (ECON@UCL) and associated support services, in the completion of this work. This study was also supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

Research Groups and Themes

  • Bristol Population Health Science Institute
  • Organic & Biological

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