An international consortium of scientists has completed a draft sequence of the genome of the rhesus macaque, a species of non-human primate that is widely used for creating models of human diseases and infections. The study paves the way for researchers to watch disease progression at the genetic level in macaques, a close relative of humans. The findings, which appear in the April 13 issue of Science, will also teach us more about how humans and other primates evolved into distinct species.
The rhesus macaque genome is the product of a deliberate effort by scientists to bring macaque biology research into the 21st century. Several years ago, University of Washington microbiologist Dr. Michael Katze and his colleague, Dr. Jeffrey Rogers, a researcher at the Southwest Foundation for Biomedical Research in San Antonio, Texas, publicly called for the sequencing project and hosted a research symposium in Seattle to discuss how to improve the understanding of macaque biology. Unlocking the rhesus macaque genome, they argued, would give researchers more powerful tools in understanding the processes of disease and infection in an animal model that is much more closely related to humans than other disease-model organisms, like mice.
“This increases dramatically the sorts of studies that we’ll be able to do,” explained Katze, a professor of microbiology at the UW and researcher in the Washington National Primate Research Center’s Functional Genomics and Infectious Disease division. He also assisted in the sequencing project. “This will allow us to analyze in a genetic microarray what’s going on at the genetic level in tissue affected by disease. For the first time, you’ll be able to do everything in non-human primates that you can only do in humans and mice now.”
The genome sequence will also help scientists conduct functional genomics research, in which they monitor how much particular genes are activated, or expressed, during the progression of a disease or infection. Proteomics researchers will also benefit from this, as they will now be able to learn a great deal more about biologically and medically significant proteins, added Dr. Robert Palermo, a research scientist in Katze’s lab. They will be able to study particular proteins involved in the macaque’s immune-system response to an infection of the pandemic influenza virus, for example, which may help us understand why the virus makes the immune system overreact and harm the infected host.
Another UW faculty member, genome scientist Dr. Evan Eichler, was also involved in the sequence analysis effort. Eichler and his colleagues looked at the large-scale structural organization of the macaque genome, and how that structure differs from that of humans and other primates. They found that compared to humans and chimpanzees, macaques seem to have fewer so-called genome segmental duplications, where a particular chunk of genetic code is repeated over and over again for a large section of the genome.
They also found that the pattern of macaque segmental duplications differed significantly from that of the human genome, and that many of these regions contained genes related to immune system response. The findings could have significant implications in microbiology and virology research, as the rhesus macaque is widely used as a model organism for studying immune response to viral infections, like influenza and HIV.
“The rhesus macaque will still be a model organism of choice for studying immune system response, but this means that we need to have a better understanding of how differences in macaque immune system genes and genome organization translate into functional differences in immune response,” said Eichler, associate professor of genome sciences at the UW and a Howard Hughes Medical Institute investigator. “The important part of this finding is that we know now where to focus our efforts — these segments of the genome with duplications and structural changes need to be studied further and resolved to a higher standard of quality. Hopefully, by studying these areas of the genome we can learn more about how a macaque may respond differently to an infection than a human.”
The rhesus macaque project also gives researchers another primate genome with which to study the evolution of humans and other primates. In 2005, scientists sequenced the genome of the chimp, our closest genetic relative. Having two close relatives — chimps and humans — and one that is further away — the rhesus macaque — will give researchers a better chance to learn more about the evolution of the primate genome.
Since the species split from each other millions of years ago, they can compare the genomes of the different species to see similarities and differences, and see which portions of the genome were conserved across the different species. Such research will help us learn what parts of the human genome are unique to humans and may have given us an evolutionary advantage over other primates.
The rhesus macaque genome project included nearly 200 scientists at more than 30 institutions around the world. It took about 2 1/2 years to sequence and assemble the genome, analyze results, and publish the findings. The study is featured in five research articles in a special issue of the journal Science.