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Searching for differences. Researchers have discovered three human genes that help distinguish us from chimps.

RIA Novosti/Alamy

Genes That Make Us Human

Finding genes that have evolved in humans among our genome's 3 billion bases is no easy feat. But now, a team has pinpointed three genes that arose from noncoding DNA and may help make our species unique.

Most genes have deep histories, with ancestors that reach down into the tree of life, sometimes all the way back to bacteria. The gradual increase from the few thousand genes in a bacterium to the tens of thousands of genes in a person came primarily through genome- and gene-duplication events, which created extra sets of genes free to evolve new sequences and new functions. Much of this duplication happened long before humans evolved, though some duplications occurred in the human lineage to create exclusively human twins of existing genes.

But in 2006, geneticists showed for the first time that they could identify truly novel genes. In fruit flies, they came across five young genes that were derived from "noncoding" DNA between existing genes and not from preexisting genes. As a result, other researchers started looking for novel genes in other species.

Meanwhile, while looking for gene duplications in humans, geneticists Aoife McLysaght and David Knowles of Trinity College Dublin kept coming across genes that seemed to have no counterparts in other primates, suggesting that new genes arose in us as well. To determine which of these genes with no counterparts were de novo genes, McLysaght and Knowles first used a computer to compare the human, chimp, and other genomes. They eliminated all but three of the 644 candidates because their sequence in the database was not complete--or they had equivalents in other species.

Next, they searched the chimp genome for signs of each gene's birth. "We strove hard to identify the noncoding DNA that gave rise to the gene," McLysaght says. Only by finding that DNA could they be sure that the gene wasn't already present in the chimp genome but was somehow unrecognizable to gene-finding programs. At three locations where the chimp and human genomes were almost identical, telltale mutations indicated that it was impossible to get a viable protein from the chimp DNA sequence. In contrast, the human version of each sequence had mutations that made it a working gene, the researchers report online tomorrow in Genome Research.

The researchers were able to verify that the genes worked by checking messenger RNA databases and protein surveys done by other scientists. They are now using antibodies to find out where in the cells these proteins are active and are trying to disable the genes in cells to tease out their functions.

The researchers analyzed only a subset of the human genome. Extrapolating to the full genome, they think humans have evolved at least 18 new genes. That's a small number compared to our total of 24,000 but nonetheless an important one. "The distinction between humans and other apes must lie somewhere in the small genetic differences between the species," says McLysaght.

Unlike duplicated genes, these are genes that "they really knew are human-specific," says Laurent Duret, a molecular evolutionary biologist at the University of Lyon in France. When he first heard about this project, he was skeptical, but not anymore. "It's the first convincing evidence of a real innovation in humans."

These three young genes join several hundred other uniquely human genomic features, including gene duplications, that provide tantalizing hints of what makes us human. But, says evolutionary biologist Gregory Wray of Duke University in Durham, North Carolina, researchers still have no clue what most of these genes do.