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Hillsboro-based team leads DNA breakthrough

A team led by a Hillsboro-based Oregon Health & Science University researcher has sequenced and annotated the genome of the only ape whose DNA had yet to be sequenced — the gibbon, an endangered small ape that inhabits the tropical forests of Southeast Asia.Photo Credit: COURTESY PHOTO - Lucia Carbone, Ph.D., an assistant professor of behavioral neuroscience in the OHSU School of Medicine has been working on a genome sequencing project at OHSUs Oregon National Primate Research Center in Hillsboro.

The team’s work, published in the Sept. 11 edition of Nature, gives scientists new insight into the evolution of the gibbon genome and its extraordinary number of chromosomal rearrangements. Chromosomal rearrangements are structural changes in the DNA that are often problematic in other species — including causing cancer in humans — but seem to have happened in gibbons at a very high frequency. The genome sequencing work also provides new details on the family tree and evolutionary history of the gibbon lineage that has been a longstanding source of debate. Photo Credit: COURTESY PHOTO - Because apes -- such as these gibbons from Southeast Asia -- are genetically similar to humans, studying them helps researchers understand genetic factors in human health and disease.

“We do this work to learn as much as we can about gibbons, which are some of the rarest species on the planet,” said Lucia Carbone, Ph.D., assistant professor of behavioral neuroscience in the OHSU School of Medicine and an assistant scientist in the Division of Neuroscience at OHSU’s Oregon National Primate Research Center on Northwest 185th Avenue in Hillsboro. “But we also do this work to better understand our own evolution and get some clues on the origin of human diseases.”

Additionally, the team uncovered some genetic clues on how gibbon species over millions of years developed longer arms and powerful shoulder and arm tendons — important for these tree-dwelling primates whose main mode of locomotion is swinging from tree to tree in the dense tropical forest.

The team’s work gives science new insight into the human genome — since apes are so genetically similar to humans. Unraveling primate genomes is vitally important as researchers try to understand the genetic factors in human health and disease.

Carbone worked on the project for more than two years, in collaboration with scientists at the Human Genome Sequencing Center at Baylor College of Medicine in Houston, Texas, and The Genome Institute at Washington University in St. Louis, Mo. Other collaborators on the project included scientists from the University of Arizona, the University of Washington and international labs from Spain, Italy and Germany.

Gibbons, together with the other apes — orangutans, gorillas, chimpanzees and bonobos — are the closest relatives to humans. Humans and these apes all belong to the “superfamily” called Hominoidea. But unlike other apes and humans, gibbons have undergone a high number of chromosomal rearrangements as they have evolved.

“You might think about chromosomes as constructions made of different plastic toy bricks. In the rearrangement, one or more toy pieces separate from the others and reattach in a different orientation or location. Or, they might get lost or duplicated,” said Carbone. “We know that these types of events have been occurring in the other apes, including humans, but gibbons show a much higher frequency. One of our goals while analyzing the genome was to try to identify the cause of this instability.”

Cancer in humans

Such chromosomal rearrangements can cause major problems in cells, and can contribute to birth defects and cancer in humans — but they seem to have been well tolerated by gibbons. The gibbon genome will now be a tool to better understand the mechanisms behind these “errors.”

“This is the last ape to be sequenced and the end of an era in human comparative genomics,” said Tomas Marques-Bonet, evolutionary geneticist at Institut de Biologia Evolutiva and the National Center of Genomic Analysis in Barcelona, Catalonia, Spain, and co-author on the paper. “Now we have tools — the genomes — for all the closest species to humans.”

As part of the project, the team sequenced the whole genome of eight different gibbon species using next-generation sequencing and revealed more about the order in which the four different gibbon genera — or a group of species — diverged from each other. While in most cases it is possible to determine the order in which different species diverged from each other, this is not the case for gibbons.

Evolutionary biologists within the team found that the four gibbon genera diverged almost instantaneously about 4 million years ago. That prevents scientists from determining the order in which they separated from each other.

Around that time, there were major changes in the tropical and subtropical forests and significant shifts in sea levels in the territory occupied by the gibbons. Those geographical changes likely contributed to the rapid divergence of the gibbon genera by generating isolation between groups. Isolation is one of the major forces to drive the rise of new species.

“We hope that by learning more about the genome of these species we will also be able to implement better strategies for their conservation — as some of these species are critically endangered and about to disappear,” Carbone said.

— Todd Murphy is a senior communications specialist for Oregon Health & Science

University in Portland and the former managing editor of the Portland Tribune.


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