MBE Advance Access originally published online on June 1, 2009
Molecular Biology and Evolution 2009 26(9):1993-2003; doi:10.1093/molbev/msp108
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Research Articles |
A Natural History of FUT2 Polymorphism in Humans
* Institut de Biologia Evolutiva (CSIC-UPF), CEXS-UPF-PRBB, Barcelona, Catalonia, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain
Etablissement Français du sang Centre Atlantique, Tours, Cedex 1, France
Laboratoire d‘Immunogénétique Moléculaire (EA3034, IFR30), Faculté de Médecine de Rangueil, Université Paul Sabatier (UPS), Toulouse Cedex 4, France
E-mail: jaume.bertranpetit{at}upf.edu.
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 nonsecretor phenotype (se), because they cannot express ABO antigens in secretions. Multiple independent mutations have been shown to be responsible for the nonsecretor 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. Although frequencies of secretor and nonsecretor 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 • nonsecretor phenotype • humans • global diversity
1 Present address: Centre de Recherche, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.