A team led by University of Washington researchers has taken a second turn at sequencing the gorilla genome, putting together puzzle pieces that didn’t match up the first time around.
The results are likely to bring about revisions in the evolutionary tale of the western lowland gorilla, and where it fits in the primate family tree that includes us humans.
“I believe there is far more genetic variation than we had previously thought. The first step is finding it,” UW geneticist Evan Eichler, the senior author of a research paper on the project published by the journal Science, said in a news release.
One of the co-authors from UW, Christopher Hill, told GeekWire in an email that the new research is part of an effort to create a comprehensive catalog of the genetic differences between humans and other great apes.
“The differences between species may aid researchers in identifying regions of the human genome that are associated with cognition, behavior and neurological diseases,” Hill said. “Having complete and accurate reference genomes to compare allows researchers to uncover these differences.”
Western lowland gorillas live in West Africa, with the largest concentration in the Republic of Congo. The first version of the species’ genome was published four years ago and has served as a useful tool for comparative analysis. But the final genome consisted of 400,000 fragments of DNA, and some of the genetic information was lost in the process of matching up all those fragments.
Eichler and his colleagues sequenced a brand-new genome, using the DNA in a blood sample drawn from a gorilla named Susie while she was at Chicago’s Lincoln Park Zoo. (She now lives at the Columbus Zoo and Aquarium in Ohio.)
The researchers took advantage of improved genome-reading technologies, including a platform called SMRT and tools known as Falcon and QUIVER, to assemble “long-read” strings of DNA. The new approach reduced the number of fragments from 400,000 to a more manageable 1,700.
The effort turned up thousands of coding regions and regulatory elements that had been missed the first time around. The updated genome shows marked dissimilarities between humans and gorillas when it comes to functions such as sensory perception, insulin regulation, the immune system and reproduction.
The variations also suggest that 50,000 years ago, the species went through a population bottleneck that was more dramatic than previously thought. A closer look at genetic variations could provide new insights into how disease, climate change and human activity have been affecting lowland gorilla populations.
“I think the take-home message is that the new genome technology and assembly bring us back to the place we should have been 10 years ago,” Eichler said.
The results confirm that gorillas rate closely behind chimpanzees and bonobos in their genetic similarity to humans. But in order to get a better fix on the full range of genetic variation, the genomes of other species will have to be redone using the long-read techniques as well.
“We definitely expect many of the genomes already available will be resequenced with long-read technology someday,” Hill said. “The amount of previously unseen structural variation is staggering.”
The technology is still too expensive for routine use, however.
“At $80,000 a pop, the price is not yet right today for clinical sequencing of human genomes using the long reads,” Eichler said. “Given a few years of cost reduction and further advances in technology, I am willing to bet this is the way we will sequence human genomes to discover disease-causing mutations in the future.”
In addition to Eichler and Hill, the authors of “Long-Read Sequence Assembly of the Gorilla Genome” include David Gordon, John Huddleston, Mark Chaisson, Zev Kronenberg, Katherine Munson, Maika Malig, Archana Raja, Carl Baker and Jay Shendure from UW; Ian Fiddes, Joel Armstrong, Mark Diekhans, Benedict Paten and David Haussler from the University of California at Santa Cruz; LaDeana Hillier and Richard Wilson from Washington University School of Medicine in St. Louis; and Christopher Dunn and Chen-Shan Chin from Pacific Biosciences of California.