Glycobiology Advance Access originally published online on February 13, 2009
Glycobiology 2009 19(6):583-591; doi:10.1093/glycob/cwp017
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Human pseudogenes of the ABO family show a complex evolutionary dynamics and loss of function
3 Institut de Biologia Evolutiva (CSIC-UPF), CEXS-UPF-PRBB, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain
4 Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
5 Laboratoire d’Immunogénétique Moléculaire, Faculté de Médecine de Rangueil, Université Paul Sabatier, Bâtiment A2, 31062 Toulouse Cedex 4, France
6 Etablissement Français du sang Centre Atlantique, 50 avenue Marcel Dassault, BP 40661, 37206 Tours cedex 3, France
7 CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
1 To whom correspondence should be addressed: Tel: +34 933160845; Fax: +34 933160901; e-mail: jaume.bertranpetit{at}upf.edu
Received on December 27, 2008; revised on February 5, 2009; accepted on February 5, 2009
The GT6 glycosyltransferases gene family, that includes the ABO blood group, shows a complex evolution pattern, with multiple events of gain and loss in different mammal species. In humans the ABO gene is considered the sole functional member although the O allele is null and is fixed in certain populations. Here, we analyze the human GT6 pseudogene sequences (Forssman, IGB3, GGTA1, GT6m5, GT6m6, and GT6m7) from an evolutionary perspective, by the study of (i) their diversity levels in populations through the resequencing analysis of European and African individuals; (ii) the interpopulation differentiation, with genotyping data from a survey of populations covering most of human genetic diversity; and (iii) the interespecific divergence, by the comparison of the human and some other primate species sequences. Since pseudogenes are expected to evolve under neutrality, they should show an evolutionary pattern different to that of functional sequences, with higher levels of diversity as well as a ratio of nonsynonymous to synonymous changes close to 1. We describe some departures from these expectations, including selection for inactivation in IGB3, GGTA1, and the interesting case of FS (Forssman) with a probable shift of its initial function in the primate lineage, which put it apart from a pure neutral pseudogene. These results suggest that some of these GT6 human pseudogenes may still be functional and retain some valuable unknown function in humans, in some case even at the protein level. The evolutionary analysis of all members of the GT6 family in humans allows an insight into their functional history, a process likely due to the interaction of the host glycans that they synthesize with pathogens; the past process that can be unraveled through the footprints left by natural selection in the extant genome variation.
Key words: ABO blood group / glycosyltransferase / GT6 gene family / natural selection / pseudogene
2 Present address: Ste Justine Hospital Research Centre, Department of Pediatric, Faculty of Medicine, University of Montreal, Montreal, Quebec H3T 1C5, Canada.