![\"Ahmet](\"https:\/\/www.salk.edu\/wp-content\/uploads\/2013\/01\/Gage646.jpg\")
<\/p>\nFrom left: Salk scientists Ahmet Denli, Carol Marchetto, I\u00f1igo Narvaiza and Fred Gage\n <\/p>\n
\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n
\n“Comparing human, chimpanzee and bonobo cells can give us clues to understand biological processes, such as infection, diseases, brain evolution, adaptation or genetic diversity,” says senior research associate I\u00f1igo Narvaiza, who led the study with senior staff scientist Carol Marchetto at the Salk Institute in La Jolla. “Until now, the sources for chimpanzee and bonobo cells were limited to postmortem tissue or blood. Now you could generate neurons, for example, from the three different species and compare them to test hypotheses.”\n <\/p>\n
\nIn the new study, published online October 23, 2013, in the journal Nature<\/a><\/em>, scientists found disparities in the regulation of jumping genes or transposons\u2014DNA elements that can copy and paste themselves into spots throughout the genome\u2014between humans and non-human primate cells. Jumping genes provide a means to rapidly shuffle DNA and might be shaping the evolution of our genomes, the scientists say.\n <\/p>\n \nWorking in the lab of Salk’s Fred Gage<\/a>, the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease, Narvaiza, Marchetto and their colleagues identified genes that are differentially expressed between iPSCs from humans and both chimpanzees and bonobos.\n <\/p>\n \nTo the group’s surprise, two of those genes code for proteins that restrict a jumping gene called long interspersed element-1 or L1, for short. Compared with non-human primate cells, human iPSCs expressed higher levels of these restrictors, called APOBEC3B and PIWIL2. “We weren’t expecting that,” Marchetto says. “Those genes caught our eyes, so they were the first targets we focused on.”\n <\/p>\n \nL1 and a handful of other jumping genes are abundant throughout our genomes. Where these bits of DNA insert themselves is hard to predict, and they can produce variable effects. For example, they might completely disrupt genes, modulate them, or cause them to be processed into entirely new proteins.\n <\/p>\n \nUsing L1 tagged with a fluorescent marker, the group observed higher numbers of fluorescent iPSCs from non-human primates compared with humans. In separate experiments, they produced iPSCs with too much or too little APOBEC3B and PIWIL2, finding\u2014as expected\u2014that an excess of the two proteins dampened the mobility and reduced the appearance of newly inserted DNA in the non-human primate cells.\n <\/p>\n This microscope image shows induced pluripotent stem cells (iPSCs) from our closest living relatives.\n <\/p>\n \nSkin cells from bonobos (pigmy chimps) were reprogrammed to pluripotent stem cells, an advance that allows scientists to study the differences between the neurons of humans and chimps. The colors show different aspects of the cells’ molecular components.\n <\/p>\n \nImage: Courtesy of Carol Marchetto, Salk Institute for Biological Studies\n<\/p>\n<\/div>\n \nThese results suggested that L1 elements insert themselves less often throughout our genomes. Indeed, looking at genomes of humans and chimpanzees that had already been sequenced, the researchers found that the primates had more copies of L1 sequences than did humans.\n <\/p>\n \nThe question that remains is what would be the impact of differences in L1 regulation? “It could mean that we have gone, as humans, through one or more bottlenecks in evolution that decrease the variability present in our genome,” says Marchetto, though the hypothesis is admittedly hard to prove. It is known, however, that humans’ genomes are less variable than chimpanzees’.\n <\/p>\n \nThe new study provides proof of concept that the iPSC technology can be used to understand some of the evolutionary differences between humans and non-human primates, says Narvaiza. The group plans to make technology, and all the data, available to the broader research community\u2014which is especially helpful now that great ape research is severely restricted in the United States and abroad\u2014so that other scientists can learn about primates using non-invasive, ethically sound methods.\n <\/p>\n \nThe team plans to differentiate the stem cells into other tissues, such as neurons, and compare how the cells from different species behave. They will also use the iPSC technology to investigate how chimpanzees might differ from people in susceptibility to \u764c\u75c7<\/a>, genetic diseases<\/a> and viral infection.\n <\/p>\n \nOther researchers on the study were Ahmet Denli, Christopher Benner, Thomas Lazzarini, and Apu\u00e3 Paquola of the Salk Institute for Biological Studies; Jason Nathanson \nThe work was supported by the National Institutes of Health<\/a>, the G. Harold & Leila Y. Mathers Foundation<\/a> and the Leona M. and Harry B. Helmsley Charitable Trust<\/a>.\n<\/p>\n \nFaculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[76],"disease-research":[],"class_list":["post-2457","disclosure","type-disclosure","status-publish","hentry","faculty-rusty-gage"],"acf":[],"yoast_head":"\n![\"pluripotent](\"https:\/\/www.salk.edu\/wp-content\/uploads\/2013\/01\/646.jpg\")
<\/p>\n
\nand Gene Yeo of the University of California San Diego, Department of Cellular and Molecular Medicine; Keval Desai of the University of California San Diego, Division of Biological Sciences; Roberto Herai and Alysson Muotri of the University of California San Diego, School of Medicine; Matthew Weitzman of the Department of Pathology and Laboratory Medicine at the University of Pennsylvania Perelman School of Medicine; and senior and corresponding author Fred H. Gage of the Salk Institute and Center for Academic Research and Training in Anthropogeny.\n<\/p>\n
\nAbout the Salk Institute for Biological Studies:<\/strong>
\nThe Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.\n<\/p>\n