First study hints at insights to come from genes unique to humans

When Stahl and colleagues determined in 2006 that the TBC1D3 gene is only found in hominoids, their curiosity was piqued. Evolution, Stahl notes, naturally tends to retain genes involved in the most important components of metabolism. If one of these genes mutated too dramatically, that would lead to an organism so sickly that it wouldn't survive long enough to perpetuate the mutation in its descendants. So evolution "conserves" these genes, retaining them largely unchanged as one species evolves into another.

Therefore, if the genome is compared to an automobile, human-only genes are unlikely to be adding new wheels. But they could, for example, be contributing a new anti-lock braking system: a regulatory function that fine-tunes essential processes originally established millennia ago in other species.

Stahl found evidence that this is the case in TBC1D3. Human DNA has eight copies or paralogs of the TBC1D3 gene. His lab showed that the increased levels of the protein made by one of the paralogs makes human cells grow more rapidly. When they transplanted the gene for the protein into mouse cells, it had the same effect.

A closer look showed that the protein from the TBC1D3 paralog delays a process that labels growth factor receptors for breakdown, prolonging the time that their signal is active.

He also found evidence that the protein was helping to activate RAS, another gene whose protein is commonly found in human cancers.

Stahl and his colleagues plan additional research to learn whether the other paralogs of TBC1D3 have different roles. He also has several ideas for learning more about the functions of human-only genes.

"We might try an organ-by-organ approach, looking to see if any genes specific to a particular organs, such as fat, are specific to humans," he says. "We also should probably look at crystallizing the proteins from some of these genes, which can tell us more about what they interact with."

There may be human diseases where these genes are mutated or missing, Stahl speculates. The effects of such conditions could provide important clues to what the humans-only genes do.

"It's also going to be very interesting for evolutionary biologists to try to develop a sense for where these humans-only genes come from," Stahl says. "The building blocks of these genes may be present but not active in earlier species."

Wainszelbaum MJ, Charron AJ, Kong C, Kirkpatrick DS, Srikanth P, Barbieri MA, Gygi SP, Stahl PD. The hominoid-specific oncogene TBC1D3 activates RAS and modulates EGF receptor signaling and trafficking. Journal of Biological Chemistry, online publication.