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Dead Gene Comes Back To Life In Humans

Date:
March 11, 2009
Source:
Public Library of Science
Summary:
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.
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FISH analysis of IRGM. The figure shows examples of FISH experiments on Hs (Homo sapiens), Rh (Macaca mulatta), Cja (Callithrix jacchus) and Lca (Lemur catta), with the use of human fosmid clone WIBR2-3607H18 (A, B, C) and lemur species-specific BAC clone LB2-77B23 (D).
Credit: Bekpen et al. Death and Resurrection of the Human IRGM Gene. PLoS Genet, 5(3): e1000403 DOI: 10.1371/journal.pgen.1000403

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.


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The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Bekpen C, Marques-Bonet T, Alkan C, Antonacci F, Leogrande MB, et al. Death and Resurrection of the Human IRGM Gene. PLoS Genet, 5(3): e1000403 DOI: 10.1371/journal.pgen.1000403

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Public Library of Science. "Dead Gene Comes Back To Life In Humans." ScienceDaily. ScienceDaily, 11 March 2009. <www.sciencedaily.com/releases/2009/03/090305204321.htm>.
Public Library of Science. (2009, March 11). Dead Gene Comes Back To Life In Humans. ScienceDaily. Retrieved May 23, 2015 from www.sciencedaily.com/releases/2009/03/090305204321.htm
Public Library of Science. "Dead Gene Comes Back To Life In Humans." ScienceDaily. www.sciencedaily.com/releases/2009/03/090305204321.htm (accessed May 23, 2015).

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