October 24, 2013
Stem Cells Reveal Key Differences Between Apes And Humans
redOrbit Staff & Wire Reports - Your Universe Online
For the first time, scientists from the Salk Institute for Biological Studies have taken stem cells from chimpanzees and bonobos and turned them into induced pluripotent stem cells (iPSCs), and their work has helped to highlight some of the differences between humans and non-human primates.
This type of cell, which has the ability to form any other type of cell or tissue in the body, can be used to model diseases that would normally be difficult to obtain from a living person or animal, the researchers said. The Salk Institute team, however, is using the iPSCs to compare and contrast the cells of humans with those of our closest living relatives – the great apes with whom we share about 99 percent of our genome.
“Comparing human, chimpanzee and bonobo cells can give us clues to understand biological processes, such as infection, diseases, brain evolution, adaptation or genetic diversity,” senior research associate Iñigo Narvaiza explained. “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.”
Narvaiza and senior staff scientist Carol Marchetto studied the iPSCs obtained from the great ape species. After comparing them to human stem cells, they discovered disparities in the regulation of so-called 'jumping genes' or transposons - DNA elements that can essentially copy and paste themselves into various locations in the genome - between the two types of creatures.
These so-called jumping genes give scientists a way to quickly shuffle DNA, and could possibly be shaping the way in which our genomes evolve, the study authors said. They found genes that are differentially expressed between human iPSCs and similar cells from both chimpanzees and bonobos.
“To 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,” the researchers reported. “Compared with non-human primate cells, human iPSCs expressed higher levels of these restrictors, called APOBEC3B and PIWIL2.”
“L1 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,” they added.
Using L1 that was tagged with a fluorescent marker, Narvaiza, Marchetto and their associates observed lower numbers of fluorescent iPSCs from humans than from non-human primates. In further research, the team produced iPSCs that had either too much or too little APOBEC3B and PIWIL2, and as they expected, elevated levels of those proteins hampered the mobility and reduced the appearance of DNA that had just been inserted into the ape cells.
“These 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,” the Institute explained. “The 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,” Marchetto said. However, the researchers admit that this hypothesis would be difficult to prove, though it has been established that the chimpanzee genomes is more variable than our own.
Narvaiza said that their research serves as proof-of-concept that iPSC technology can be used to understand evolutionary differences between human and non-human primates. They plan to make their technology and data available to the research community at large, and also plan to differentiate the stem cells into different types of tissues for cross-species comparison.