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Research Article

Death and Resurrection of the Human IRGM Gene

  • Cemalettin Bekpen,

    Affiliations: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America, Howard Hughes Medical Institute, Seattle, Washington, United States of America

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  • Tomas Marques-Bonet,

    Affiliations: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America, Institut de Biologia Evolutiva (UPF-CSIC), Barcelona, Spain

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  • Can Alkan,

    Affiliations: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America, Howard Hughes Medical Institute, Seattle, Washington, United States of America

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  • Francesca Antonacci,

    Affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America

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  • Maria Bruna Leogrande,

    Affiliation: Universita' degli Studi di Bari, Bari, Italy

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  • Mario Ventura,

    Affiliation: Universita' degli Studi di Bari, Bari, Italy

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  • Jeffrey M. Kidd,

    Affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America

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  • Priscillia Siswara,

    Affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America

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  • Jonathan C. Howard,

    Affiliation: Institute of Genetics, University of Cologne, Cologne, Germany

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  • Evan E. Eichler mail

    eee@gs.washington.edu

    Affiliations: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America, Howard Hughes Medical Institute, Seattle, Washington, United States of America

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  • Published: March 06, 2009
  • DOI: 10.1371/journal.pgen.1000403

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Copy of the press release originally distributed on March 2, 2009

Posted by PLoS_Genetics on 31 Mar 2009 at 14:38 GMT

A dead gene comes back to life in humans

Researchers have discovered that a long-defunct gene was resurrected during the course of human evolution. This is believed to be the first evidence of a doomed gene – infection-fighting human IRGM – making a comeback in the human/great ape lineage. The study, led by Evan Eichler's genome science laboratory at the University of Washington and the Howard Hughes Medical Institute, is published March 6 in the open-access journal PLoS Genetics.

The truncated IRGM gene is one of only two genes of its type remaining in humans. The genes are Immune-Related GTPases, a kind of gene that helps mammals resist germs like tuberculosis and salmonella that try to invade cells. Unlike humans, most other mammals have several genes of this type. Mice, for example, have 21 Immune-Related GTPases. Medical interest in this gene ignited recently, when scientists associated specific IRGM mutations with the risk of Crohn's disease, an inflammatory digestive disorder.

In this latest study, the researchers reconstructed the evolutionary history of the IRGM locus within primates. They found that most of the gene cluster was eliminated by going from multiple copies to a sole copy early in primate evolution, approximately 50 million years ago. Comparisons of Old World and New World monkey species suggest that the remaining copy died in their common ancestor.

The gene remnant continued to be inherited through millions of years of evolution. Then, in the common ancestor of humans and great apes, something unexpected happened. Once again the gene could be read to produce proteins. Evidence suggests that this change coincided with a retrovirus insertion in the ancestral genome.

"The IRGM gene was dead and later resurrected through a complex series of structural events,” Eichler said. "These findings tell us that we shouldn't count a gene out until it is completely deleted."

The structural analysis, he added, also suggests a remarkable functional plasticity in genes that experience a variety of evolutionary pressures over time. Such malleability may be especially useful for genes that help in the fight against new or newly resistant infectious agents.


No competing interests declared.

RE: Copy of the press release originally distributed on March 2, 2009

PLoS_Genetics replied to PLoS_Genetics on 31 Mar 2009 at 14:46 GMT

The following links provide access to some of the news/blog coverage since publication. The journal is not responsible for the content of external sites; some external sites may require registration to view the full article; readers are welcome to judge the merits of each piece, considered in conjunction with the open-access article (http://www.plosgenetics.o...) for themselves.

- Nature News: http://www.nature.com/new...

- Science Now: http://sciencenow.science...

- New Scientist: http://www.newscientist.c...

- The Scientist: http://www.the-scientist....

- io9: http://io9.com/5165457/ar...

No competing interests declared.