A dead gene comes back to life in humans

Mar 06, 2009
The figure summarizes the death and resurrection of Human IRGM gene. The functional gene (green) and the non-functional dead copy (red) are shown within the context of the generally accepted primate phylogeny. Genetic analyses suggest that that gene died approximately 50 million years ago as a result of genetic changes that disrupted its expression and function. In all Old World and New World monkeys, the gene is non-functional. However, in the ancestor of the apes and humans, mutations occurred to restore its function. This restoration of the protein's reading frame was gradual and some species such as gibbon and orangutan carry a living and dead copy.

(PhysOrg.com) -- 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 sciences laboratory at the University of Washington and the Howard Hughes Institute, is published March 6 in the open access journal PLoS Genetics, in the article, "Death and Resurrection of the Human IRGM Gene." The first author of the study is Cemalettin Bekpen, a UW senior fellow in genome sciences.

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.

More information: Bekpen C, Marques-Bonet T, Alkan C, Antonacci F, Leogrande MB, et al. (2009) Death and Resurrection of the Human IRGM Gene. PLoS Genet 5(3): e1000403. doi:10.1371/journal.pgen.1000403, www.plosgenetics.org/article/i… journal.pgen.1000403

Provided by University of Washington

Explore further: Could ibuprofen be an anti-aging medicine? Popular over-the counter drug extends lifespan in yeast, worms and flies

add to favorites email to friend print save as pdf

Related Stories

Genes tell story of birdsong and human speech

Dec 11, 2014

His office is filled with all sorts of bird books, but Duke neuroscientist Erich Jarvis didn't become an expert on the avian family tree because of any particular interest in our feathered friends. Rather, ...

How fast you age depends on your parents

Dec 11, 2014

In the hunt for better knowledge on the aging process, researchers from Lund University have now enlisted the help of small birds. A new study investigates various factors which affect whether chicks are ...

Recommended for you

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Sepp
4 / 5 (1) Mar 07, 2009
Any chance of bringing back to life the gene that lets humans manufacture vitamin C as part of normal metabolism, as is the case with most animals?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.