A gene's second coming

A long-defunct gene that is now involved in Crohn's disease was resurrected over the course of human evolution after being "dead" for millions of years, according to a linkurl:report;http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000403 published online today (Mar. 5) in __PLoS Genetics__. "This is probably the first example of a gene coming back from the dead after being gone for 25 million years," linkurl:Evan Eichler,;http://www.gs.washington.edu/faculty/eichler.htm a genome researcher at the University of Washington in Seattle who led the study, told __The Scientist__. "It's a rare but nonetheless very instructive incident of a dead copy of a gene being reactivated," said linkurl:Daniel Fairbanks,;http://lifesciences.byu.edu/old/FacStaff/default.aspx?ID=177 a geneticist at Utah Valley University in Orem who was not involved in the research. "It really documents something that's unusual." Eichler and his colleagues reconstructed the evolutionary history of an immune-related gene called __IRGM__ among humans and seven other primate species. They discovered that a cluster of related gene copies found in the lower primates -- which include lemurs, lorises, and tarsiers -- had contracted to a single copy in the lineage leading to apes and monkeys, some 40 to 50 million years ago. Further sequence analysis showed that a retrotransposon insertion knocked out the single __IRGM__ gene in the higher primates, rendering it non-operational. But while it stayed that way in both Old World and New World monkeys, humans and great apes experienced a genetic rebirth around 20 million years ago after a retrovirus jumped back into the gene and created a new functional promoter. "For all these types of events to have occurred, it's really quite remarkable," said Eichler. "We have this idea of a gene as being fairly sacrosanct, but here's something that has changed multiple times over the course of evolution with what appears to be different consequences. To me that's a big surprise." linkurl:Ramnik Xavier,;http://ccib.mgh.harvard.edu/founders-xavier.htm an immunologist at Massachusetts General Hospital in Boston who was not involved in the research, described the paper as "spectacular." "It tells us about how this particular __IRGM__ gene has undergone extensive regulation throughout evolution," he said. "This paper is going to have a very big impact," added Yale University bioinformatician linkurl:Mark Gerstein,;http://bioinfo.mbb.yale.edu/ who was also not involved in the study. "There's this emerging idea that the distinction between a dead genetic element and living genetic element is not an absolute." The __IRGM__ gene is also notable because it was recently implicated by Xavier, together with linkurl:Steven McCarroll;http://www.broad.mit.edu/news/1081 of the Broad Institute and Massachusetts General Hospital, as a risk factor for Crohn's disease. In their linkurl:study,;http://www.nature.com/ng/journal/v40/n9/abs/ng.215.html the researchers showed that two different forms of __IRGM__ segregate in human populations, one of which confers susceptibility to the inflammatory digestive disorder. "Our genomes are still figuring out whether to have this gene at all, and if they do have it what to do with it," said McCarroll. "[__IRGM__] is very much a work in progress as opposed to something that evolution worked out a long time ago." Eichler's team also compared the __IRGM__ gene sequence among 12 orangutan individuals and five different gibbon species; these ape species also showed a fairly high level of variation in the form of __IRGM__ they carried. It shows "how really fluid and plastic the genome is as it evolves," said Eichler. "I don't know many genes that have done as much as this gene has in terms of changes in expression and structure." The bottom line, Eichler added: "Don't count a gene out until it's totally gone from a genome." **__Related stories:__***linkurl:Restructuring human variation;http://www.the-scientist.com/blog/display/54856/ [August 2008]*linkurl:Transcription factors help distinguish humans;http://www.the-scientist.com/news/display/23219/ [9th March 2006]*linkurl:Gene linked to Crohn's disease;http://www.the-scientist.com/article/display/19676/ [22nd May 2001]

A gene's second coming

Interested in reading more?

Become a Member of