Death and resurrection of the human IRGM gene

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• dc.contributor.author Bekpen, Cemalettinca
• dc.contributor.author Marquès i Bonet, Tomàs, 1975-ca
• dc.contributor.author Alkan, Canca
• dc.contributor.author Antonacci, Francescaca
• dc.contributor.author Leogrande, Maria Brunaca
• dc.contributor.author Ventura, Marioca
• dc.contributor.author Kidd, Jeffrey M.ca
• dc.contributor.author Siswara, Priscilliaca
• dc.contributor.author Howard, Jonathan C.ca
• dc.contributor.author Eichler, Evan E.ca
• dc.date.accessioned 2013-04-03T09:17:43Z
• dc.date.available 2013-04-03T09:17:43Z
• dc.date.issued 2009ca
• dc.description.abstract Immunity-related GTPases (IRG) play an important role in defense against intracellular pathogens. One member of this gene family in humans, IRGM, has been recently implicated as a risk factor for Crohn's disease. We analyzed the detailed structure of this gene family among primates and showed that most of the IRG gene cluster was deleted early in primate evolution, after the divergence of the anthropoids from prosimians ( about 50 million years ago). Comparative sequence analysis of New World and Old World monkey species shows that the single-copy IRGM gene became pseudogenized as a result of an Alu retrotransposition event in the anthropoid common ancestor that disrupted the open reading frame (ORF). We find that the ORF was reestablished as a part of a polymorphic stop codon in the common ancestor of humans and great apes. Expression analysis suggests that this change occurred in conjunction with the insertion of an endogenous retrovirus, which altered the transcription initiation, splicing, and expression profile of IRGM. These data argue that the gene became pseudogenized and was then resurrected through a series of complex structural events and suggest remarkable functional plasticity where alleles experience diverse evolutionary pressures over time. Such dynamism in structure and evolution may be critical for a gene family locked in an arms race with an ever-changing repertoire of intracellular parasites.
• dc.description.sponsorship This work was supported by a Marie Curie fellowship
• dc.description.sponsorship This work was supported in part by Deutsche Forschungsgemeinschaft grant SFB680 to JCH and by NIH grants GM058815 and HG002385 to EEE. TM-B is supported by a Marie Curie fellowship. EEE is an investigator of the Howard Hughes Medical Institute. The funders had no role in study design, data co/nllection and analysis, decision to publish, or preparation of the manuscript.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Bekpen C, Marques-Bonet T, Alkan C, Antonacci F, Leogrande MB, Ventura M et al. Death and resurrection of the human IRGM gene. PLoS Genet. 2009;5(3):e1000403. DOI: 10.1371/journal.pgen.1000403ca
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1000403
• dc.identifier.issn 1553-7390ca
• dc.identifier.uri http://hdl.handle.net/10230/20530
• dc.language.iso engca
• dc.publisher Public Library of Science (PLoS)ca
• dc.relation.ispartof PLOS Genetics. 2009;5(3):e1000403
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/220278
• dc.rights © Bekpen C et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution...(CC BY) (http://creativecommons.org/licenses/by/2.5/).ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/2.5/
• dc.subject.other Evolució molecular
• dc.subject.other Primats -- Genètica
• dc.subject.other Genètica humana
• dc.title Death and resurrection of the human IRGM geneca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca