A dead gene comes back to life in humans

March 6, 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: Cinnamon turns up the heat on fat cells

Related Stories

Cinnamon turns up the heat on fat cells

November 21, 2017
New research from the University of Michigan Life Sciences Institute has determined how a common holiday spice—cinnamon—might be enlisted in the fight against obesity.

NeuroExpresso: Web app enables exploration of brain cell types

November 20, 2017
An online database of gene expression profiles for 36 major types of brain cells from 12 brain regions, based on mouse data from multiple laboratories, is reported in a new paper published in eNeuro. The tool is provided ...

Researchers reveal new details on aged brain, Alzheimer's and dementia

November 21, 2017
In a comprehensive analysis of samples from 107 aged human brains, researchers at the Allen Institute for Brain Science, UW Medicine and Kaiser Permanente Washington Health Research Institute have discovered details that ...

Researchers identify a potential molecular trigger for invasiveness in prostate cancer cells

November 21, 2017
A small protein modification can trigger the aggressive migratory and invasive properties of prostate cancer cells, according to new research published on the cover of Oncotarget. The findings give greater insight into how ...

Preclinical study demonstrates promising treatment for rare bone disease

November 20, 2017
Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have led a preclinical study demonstrating that the drug palovarotene suppresses the formation of bony tumors (osteochondromas) in models of multiple ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

Recommended for you

New approach to studying chromosomes' centers may reveal link to Down syndrome and more

November 20, 2017
Some scientists call it the "final frontier" of our DNA—even though it lies at the center of every X-shaped chromosome in nearly every one of our cells.

Genome editing enhances T-cells for cancer immunotherapy

November 20, 2017
Researchers at Cardiff University have found a way to boost the cancer-destroying ability of the immune system's T-cells, offering new hope in the fight against a wide range of cancers.

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

1 comment

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.