A “ZOMBIE” gene that scientists had long considered dead and inactive is in fact alive and well, according to research by Irish scientists.
The discovery has great potential for treating leukaemia but also for detecting women at high risk of having children with spina bifida. Scientists have known about these “zombie” or pseudogenes for decades but the genes were always considered dead and inactive, said Anne Parle-McDermott, lecturer in genetics in Dublin City University’s school of biotechnology.
Dr Parle-McDermott led a research group who discovered that at least one of these pseudogenes is in fact active and producing an important biochemical needed by cells. Details of the research are published this morning in the US Proceedings of the National Academy of Sciences.
Pseudogenes are an essential part of the evolutionary process, she said. Genes often make copies of themselves, but many of the copies have mutations that render them inactive. In other cases, the mutations modify what a gene makes. Having these copied genes is extremely important, however, Dr Parle-McDermott said. “As a species, we would not evolve if that didn’t happen.”
She and her team looked at four zombie genes associated with the famous gene DHFR. This is the gene targeted with chemotherapy when treating forms of the blood cancer leukaemia. Knocking it out with drugs makes leukaemia cells die. The researchers looked at the apparently “dead” copy gene DHFRL1 and, to their surprise, discovered it was not a zombie but very much alive.
Advances in DNA-analysis techniques made it possible for them to detect that the zombie gene was working. They identified what it produces and also how this substance is used to help regulate energy production inside cells.
The finding has huge implications, given many of the thousands of known pseudogenes may not be zombies at all, she said. “It is important for a number of reasons, in the cancer field for one. It represents a new target that people didn’t know about until now.”
A combination drug therapy could target both the primary gene DHFR but also its mutant copy. “We think this might be a better treatment for cancer,” Dr Parle-McDermott said.
The finding could also be important in spina bifida. DHFR is involved in how a person’s body processes folic acid, a B vitamin that helps to protect against spina bifida. The zombie gene might offer a way to warn if a woman is at higher risk of having a baby with the condition.