Researchers at the Carnegie Institution have been researching genetic features called transposons or jumping genes since Barbara McClintock discovered them, which got her the Nobel Prize in 1983. Since then, scientists have found that they comprise around 44 percent of our DNA (though it does not seem these areas are all active). They can disrupt the genome significantly as they insert themselves within the genomes of egg or sperm cells, and can cause death depending on where they land. It’s thought that organisms have tolerated huge numbers of genetic invasions by these damaging elements over many generations. New research has indicated that stem cells react to the changes transposons induce.
Carnegie scientists found that when stem cells sense transposon activity, they increase the levels of a non-coding genetic material, piRNA (piwi-interacting RNA). That acts to suppress the activity of jumping genes and initiates a DNA repair mechanism; egg cells can then develop normally. These findings, which show how organisms may have survived many rounds of jumping gene invasions, have been reported in Developmental Cell.
The investigators used a common genetic research model, the fruit fly, for this work. It’s been established that temperature influences the sperm and egg cells of fruit flies. When it’s 77 degrees Fahrenheit, fruit fly offspring have sterile ovaries. At a temperature of 64 degrees Fahrenheit, ovaries are fertile and normally developed. Temperature also influenced the severity of the jumping gene effect.
"Because temperature had been widely known to affect sterility, we decided to quantify the rates of this jumping gene's activity at different temperatures. We discovered that the rate of jumping gene mobilization was seven times greater at 77 degrees F in ovarian stem cells, which means we can simply use temperature to control the invasion intensity from jumping genes," explained the first author of the report, Sungjin Moon.
The team was used the adult fly ovary to model the effect of jumping genes. They found that reproductive stem cells can respond to invading genetic elements by starting up a DNA damage checkpoint. Damaged DNA can then be fixed before cells divide and incorporate the damage. One component, Chk2, was found to be a critical part of the process.
DNA repair pauses while piRNA production is ramped up, so the jumping genes can be stopped. The researchers determined that the pause is essential; it can permanently silence the transposons. Normal egg production was found to resume within four days.
"Jumping gene invasion triggers catastrophic genomic instability in all organisms," added Zhao Zhang. "They greatly reduce the viability or fertility of the invaded animals and can lead to a population crisis. We believe that the ability of reproductive stem cells to rapidly adapt and restore fertility in this manner allows species to resist such a population crash. This mechanism is a lynchpin to species survival."