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NIH-Funded Scientists Publish Orangutan Genome Sequence

NIH-Funded Scientists Publish Orangutan Genome Sequence

NIH-Funded Scientists Publish Orangutan Genome Sequence

NIH-Funded Scientists Publish Orangutan Genome Sequence

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It is easy to feel a kinship with orangutans when looking into their soulful eyes and observing their socially complex behavior. Perhaps that's because orangutans and humans share 97 percent of their DNA sequence, according to an analysis of the great ape's genome published today by an international group of scientists.

Orangutans, known for their distinctive auburn hair, are primarily tree dwellers native to the Southeast Asian islands of Sumatra and Borneo. The DNA sequence published in the Jan. 27 issue of Nature is from a female Sumatran (Pongo abelii) orangutan. In addition, five Sumatran and five Bornean (Pongo pygmaeus) orangutan genomes were sequenced at a less detailed level. The orangutan is the third non-human primate to have its genome sequenced, after the chimp and rhesus macaque. Of the great apes, orangutans are the most distantly related to humans, while chimpanzees are the most closely related.

Funded in part by the National Human Genome Research Institute (NHGRI), a component of the National Institutes of Health (NIH), the study was led by scientists from the Washington University School of Medicine in St. Louis and Baylor College of Medicine, Houston.

Researchers can now leverage the orangutan genome sequence to learn more about the biology of this endangered species and to identify what has been added or deleted in the evolution of primate and human genomes that may have contributed to unique human characteristics.

"The unique evolutionary position of the orangutan can be leveraged to discover parts of the human genome that differ among primates," said NHGRI Director Eric D. Green, M.D., Ph.D. "Sequencing many primate genomes can help us define and understand the conserved DNA sequences that set humans apart from primates."

While humans and orangutans are similar at the DNA level, comparing available primate genome sequences revealed that the orangutan has evolved much more slowly than chimpanzees and humans. The orangutan genome has fewer large DNA sequence structural rearrangements than its chimpanzee and human counterparts. Large genome structural rearrangements are DNA mutations that result in large genomic segments being duplicated, deleted, inserted or inverted.
"In terms of evolution, the orangutan genome is quite special among great apes in that it has been extraordinarily stable over the past 15 million years," says senior author Richard K. Wilson, Ph.D., director of the Washington University Genome Center. "This compares with chimpanzees and humans, both of which have experienced large-scale structural rearrangements in their DNA that may have accelerated their evolution."

The researchers catalogued one type of large structural rearrangement called segmental duplications that have played a major role in restructuring other primate genomes. These large, almost identical copies of DNA are present in at least two locations of the genome and known to be associated with human diseases. Segmental duplications make up about 5 percent of human and chimpanzee genomes, but are present in only about 3.8 percent of the orangutan genome.

There are also many fewer Alu elements -- short stretches of DNA that insert themselves into a genome; these are associated with new mutations and gene recombination. The human genome possesses about 5,000 human-specific Alu elements, while the chimpanzee genome has about 2,000 chimp-specific Alu elements. Only 250 such elements were found in the orangutan genome.The lack of newer Alu elements could be one of the reasons that the orangutan genome does not have the degree of structural rearrangement found in other great apes.

Another structural oddity encountered is the presence of a neocentromere on orangutan chromosome 12. A neocentromere is a centromere that appears in a novel location. A centromere sits in the middle of and joins the two arms of a chromosome. It also helps to keep chromosomes properly aligned during the complex process of cell division. This is the first neocentromere discovered in a primate genome. One was previously found in the horse genome. Discovery of the neocentromere will help researchers understand how centromeres, and therefore chromosomes, change and evolve.

"This variant in the chromosome 12 centromere position appears in both populations of orangutan," said Kim Worley, Ph.D., an author of the study and associate professor of the Baylor College of Medicine Human Genome Sequencing Center. "It attracts centromeric proteins in the same way that a normal centromere does."  

The analysis also reveals the immense genetic diversity across and within Sumatran and Bornean orangutans. Diversity is important because it enhances the ability of populations to stay healthy and adapt to changes in the environment. The new research shows that the Sumatran and Bornean orangutans diverged some 400,000 years ago. Today, only about 50,000 Bornean and 7,000 Sumatran orangutans still live in the wild. But, in a finding that seems counter-intuitive, the scientists found the smaller population of Sumatran orangutans is genetically more diverse than the Bornean population.

"The average orangutan is still more diverse - genetically speaking - than the average human," says lead author Devin Locke, Ph.D., an evolutionary geneticist at Washington University's Genome Center. "We found deep diversity in both Bornean and Sumatran orangutans, but it's unclear whether this level of diversity can be maintained in light of continued widespread deforestation of their homes."

"It is our hope that the genome assembly and population variation data presented here provide a valuable resource to the community to aid the preservation of these precious species," according to the paper's conclusion.