About eight to twelve million years ago, the evolutionary ancestor to humans, chimpanzees, and orangutans appears to have undergone a burst of evolution, driven by duplicated sequences of DNA. This mechanism of genetic change, which has only recently come under scientific scrutiny, may have endowed primates with an evolutionary flexibility that drove the development of different great ape species, including humans.
When a stretch of DNA is mistakenly duplicated, extra copies of the gene or genes within that region are added to the genome; those genes can then mutate separately. “Duplications are really important from an evolutionary perspective because they add a lot of variation to the genome,” says Tomas Marques-Bonet, a scientist in Evan Eichler’s lab at the University of Washington, in Seattle, who led the research. “These regions are rapidly evolving.”
Most estimates of genetic similarity between humans and other primates have focused on single-letter changes to the genome as the primary basis for evolutionary change. But scientists are now discovering the importance of structural changes to the genome, which include deletions or duplications of segments of DNA between 1,000 and 100,000 letters in length. These regions are flanked by repetitive stretches that are thought to trigger errors in the cells’ DNA replication process, resulting in duplicated genes.
“It’s only recently that we have had the sequence data and the genomic tools to study this and understand its role in evolutionary history,” says George Perry, a scientist at the University of Chicago, who was not involved in the research. The chimp genome was released in 2005, and the orangutan and macaque genome projects are ongoing. In addition, scientists can now create custom-designed gene microarrays to quickly detect a large number of specific duplications.
Marques-Bonet and his colleagues analyzed the genome sequence of four primate species: humans, chimpanzees, orangutans, and macaques. Humans, chimps, and orangutans descend from the African great ape lineage, sharing a common ancestor about 12 million years ago, while macaques, classified as old-world monkeys, split from the common primate lineage more than 25 million years ago. Comparing areas of DNA duplication in the genome sequence, researchers found a burst in the rate of duplications right before orangutans split from the tree, and a second burst before chimps and humans diverged, according to research published today in the journal Nature. This increase happened even as rates of single-letter changes decreased.
Scientists are hesitant to speculate about precisely how the acceleration in the rate of duplication arose in the human and chimp lineage, and how it affected human evolution. For example, it’s not yet clear whether the duplications that occurred during this time period conferred an evolutionary advantage on their bearers. “We think that duplications make the genome more dynamic,” says Marques-Bonet. “But having a dynamic genome creates both sides of the coin: these rearrangements can be beneficial, or they can be linked to disease.” Recent research shows that duplications in the human genome play a role in a variety of diseases, including autism, schizophrenia, and mental retardation.
It’s also unclear if the acceleration seen in the chimp and human ancestor is unique. “These basic kinds of mutations have been going on for at least 90 million years,” says Nick Patterson, a geneticist at the Broad Institute, in Cambridge, MA. “The question is whether there is something unusual in what happened in human lineage; I doubt we have enough data to answer that.” This type of comparison would require genome sequences for many related mammal species.
Duplications are likely to have very different evolutionary properties than single-letter changes. Both arise from mistakes at the molecular level, which can then either help, harm, or do nothing to the reproductive fitness of the organism. Most single-letter changes fall into the neutral category. But because duplicative changes often increase the number of copies of a gene and thus potentially increase the concentration of protein that gene produces, they are more likely to exert an effect on the carrier.
In addition, while single-letter changes may make a particular protein more or less effective by slightly tweaking its structure, duplications that create additional copies of specific genes free up the new copies to evolve an entirely new purpose. “You havetwo copies that can diverge from each other,” says Perry. “One copy can then experience mutation and attain a new function that could be important for the biology of that organism.” For example, color vision in primates arose thanks to the duplication of the gene for visual pigment. “With this kind of analysis,” says Perry, “we can begin to identify other genes specific to different lineages, and then study the potential effect they might have on the biology of these species.”
Most of the duplications analyzed in the study–more than 80 percent–are shared by humans, chimps, and gorillas. But the genes in duplicated regions unique to humans are largely ones that have not yet been characterized. “We found more than 30 genes that are duplicated only in humans,” says Marques-Bonet. “But we still don’t know what they do.”