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MBE Advance Access published online on June 1, 2009
Molecular Biology and Evolution, doi:10.1093/molbev/msp108
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

A natural history of FUT2 polymorphism in humans

Anna Ferrer-Admetlla1, Martin Sikora1, Hafid Laayouni1,2, Anna Esteve1, Francis Roubinet3, Antoine Blancher4, Francesc Calafell1,2, Jaume Bertranpetit1,2 and Ferran Casals1,5

1 Institut de Biologia Evolutiva (CSIC-UPF), CEXS-UPF-PRBB, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain
2 CIBER Epidemiología y Salud Pública (CIBERESP)
3 Etablissement Français du sang Centre Atlantique, BP 52009, 37020 Tours, Cedex 1, France
4 Laboratoire d'Immunogénétique Moléculaire (EA3034, IFR30); Faculté de Médecine de Rangueil; Bâtiment A2 ; Université Paul Sabatier (UPS); 31062 Toulouse Cedex 4, France
5 Present address: Centre de Recherche, CHU Sainte-Justine, Université de Montréal, Montréal, Québec H3T 1C5, Canada

Author for correspondence: Jaume Bertranpetit, IBE-Institut de Biologia Evolutiva (UPF-CSIC), CEXS-UPF-PRBB, Doctor Aiguader, 88, 08003 Barcelona, Catalonia, Spain, Telef. +34.93.316.08.40, Fax. +34.316.09.01, jaume.bertranpetit{at}upf.edu

Received for publication November 18, 2008. Revision received March 18, 2009. Revision received May 8, 2009. Accepted for publication May 17, 2009.

Because pathogens are powerful selective agents, host cell surface molecules used by pathogens as identification signals can reveal the signature of selection. Most of them are oligosaccharides, synthesized by glycosyltransferases. One known example is balancing selection shaping ABO evolution as a consequence of both, A and B antigens being recognized as receptors by some pathogens, and anti-A and/or anti-B natural antibodies produced by hosts conferring protection against the numerous infectious agents expressing A and B motifs. These antigens can also be found in tissues other than blood if there is activity of another enzyme, FUT2, a fucosyltransferase responsible for ABO biosynthesis in body fluids. Homozygotes for null variants at this locus present the non-secretor phenotype (se), since they can not express ABO antigens in secretions. Multiple independent mutations have been shown to be responsible for the non-secretor phenotype, which is coexisting with the secretor phenotype in most populations. In this study, we have resequenced the coding region of FUT2 in 732 individuals from 39 worldwide human populations. We report a complex pattern of natural selection acting on the gene. While frequencies of secretor and non-secretor phenotypes are similar in different populations, the point mutations at the base of the phenotypes are different, with some variants showing a long history of balancing selection among Eurasian and African populations, and one recent variant showing a fast spread in East Asia, likely due to positive selection. Thus a convergent phenotype composition has been achieved through different mutations with different evolutionary histories.

Key Words: FUT2 • balancing selection • secretor phenotype • non-secretor phenotype • humans • global diversity


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