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A Genetic Tryst in the Testes

Stitching together bits and pieces didn't work out for Dr. Frankenstein, but that hasn't stopped primate genomes from trying the same approach. Every once in a while, the pieces fall into place. New work shows that a gene unique to humans and great apes arose through the joining of two unrelated genes.

About 5% of the human genome consists of segments of DNA that have been copied and, sometimes, moved. These duplications seem to have occurred during the last 35 million years, after the primate branch of the evolutionary tree split from that of other mammals. Biologists believe that the duplicate often remains adjacent to the original gene, gradually accumulating mutations and diverging until the two acquire different functions. Less common is a scenario in which part of one gene jumps into another gene. Rarer still is such a combined gene that, by some lucky alignment, happens to produce a functional protein.

Sifting through the human genome for cancer-related genes, or oncogenes, cancer biologists Daniel Haber and Charles Paulding of Harvard Medical School and their colleagues noticed a gene, USP32, whose DNA sequence looked remarkably similar to one they'd seen before: an oncogene called Tre2. Yet only half of Tre2 resembled USP32; the other half looked like a gene called TBC1D3, which codes for a poorly understood signaling protein, that itself arose by duplication. Each half encodes a functional domain, but researchers don't yet know exactly what Tre2 does, just that it causes tumors when added to mouse cells.

Unlike either of its two "parent" genes, Tre2 produces protein only in the testes. This exclusive expression in reproductive tissue, the researchers suggest, means that the protein could have contributed to the formation of new species by helping prevent hominoids from reproducing with other primates. Indeed, Tre2 seems to have arisen after mice and humans diverged: The team found that Tre2 is more similar to human USP32 than to mouse USP32. The work appears online this week in the Proceedings of the National Academy of Sciences.

The paper's strength, says evolutionary geneticist Evan Eichler of Case Western Reserve University in Cleveland, Ohio, is that it demonstrates that such a genomic rearrangement occurred recently, in evolutionary terms. Also, "the really cool thing is that you can form a gene that has a function by juxtaposing two pieces together," Eichler says.

Related sites
Daniel Haber's Web site
Evan Eichler's Web site