A team led by Oregon Health & Science University 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. Tomàs Marquès-Bonet, ICREA Research Professor and leader of the Comparative Genomics team at the CNAG and the Institut de Biologia Evolutiva (IBE) has led the Spanish contribution to the study.

The team's work, published in 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. 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.

Finally, like the DNA sequencing of other apes and non-human primates, 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.

“This is the last ape to be sequenced and the end of an era in human comparative genomics,” said Tomàs Marquès-Bonet. “Now we have tools — the genomes — for all the closest species to humans.”

Next Generation Sequencing of gibbon genomes
As part of the project, the CNAG carried out the sequencing of several whole genomes of 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 four million years ago. That prevents scientists from determining the order in which they separated from each other.

“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,” said Lucia Carbone, fist author of the paper and 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.

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.”

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.”

The intriguing role of "LAVA"
In particular, the analysis of the gibbon genome exposed an intriguing role for a new repetitive DNA sequence that emerged exclusively in the gibbon genome. It’s called the “LAVA” element and more than one thousand copies have been found in the gibbon genome. Several LAVA elements have been inserted in a group of genes that are important for guaranteeing the correct separation of chromosomes when cells divide.
“The LAVA element is an evolutionary novelty that is only present in the DNA of gibbon species,” Carbone said. “We think that it played a major role by increasing the ‘errors’ during cell division and chance for chromosomal rearrangements.”

Interestingly, many of the genes impacted by the LAVA element in gibbons are mutated in some types of tumors in human. The gibbon genome project shows that by understanding how evolution experiments with genomic rearrangement, we might then be able to apply that knowledge to human health.

“Reading the gibbon DNA is a milestone in the field of genetic sequencing because it is a species with extraordinary features that will give us the keys to understanding genomic rearrangements and translate this knowledge into clinics.” said **Ivo Gut**, director of the CNAG and co-author on the paper.

Besides the contribution of the CNAG and the Institut de Biologia Evolutiva (UPF/CSIC) and the leadership of the Oregon Health & Science University, other collaborators on the project included international labs from Italy and Germany, the Human Genome Sequencing Center at Baylor College of Medicine the Genome Institute at Washington University and scientists from the University of Arizona and the University of Washington.

Work of reference:

Gibbon genome and the fast karyotype evolution of small apes.

Photo by Heather Angel / Natural Visions: Female white-cheeked gibbon with 2 week baby