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A Natural History of FUT2 Polymorphism in Humans

AuthorsFerrer Admetlla, Anna; Sikora, Martin; Laayouni, Hafid CSIC ORCID; Esteve, Anna; Roubinet, Francis; Blancher, Antoine; Calafell, Francesc CSIC ORCID ; Bertranpetit, Jaume CSIC ORCID ; Casals, Ferran CSIC ORCID
Balancing selection
Secretor phenotype
Nonsecretor phenotype
Global diversity
Issue DateSep-2009
PublisherOxford University Press
CitationMolecular Biology and Evolution 26(9): 1993-2003 (2009)
AbstractBecause 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.
Description11 páginas, 2 figuras, 3 tablas.
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