Scientists believe the genes of virus-resistant and long-living wild bats might hold clues to treating cancer and infectious diseases in humans. The theory is that when bats started flying millions of years ago, something changed in their DNA that provides resistance to viruses and helps give them a relatively long life. The researchers hope a better understanding of bat evolution could lead to new treatments for disease and aging in humans.
An international team led by researchers from Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO) and the Beijing Genome Institute sequenced the genomes of two bat species – an Australian mega bat, the black flying fox, and a Chinese micro bat, David’s myotis. The team compared the genomes of these bats to the genomes of all other mammals, including humans, to examine similarities and differences. They found that bats can harbor deadly human viruses, such as Hendra, Nipah, Ebola and SARS, but they often don’t succumb to disease from these viruses.
Dr Chris Cowled, post-doctoral fellow at the CSIRO's Australian Animal Health Laboratory said the findings might shed light on the genetic changes associated with the evolution of flight. He said wild bats have unusual genes like P53, which is implicated in the suppression of human cancer tumors and the detection and repair of damaged DNA.
However, the scientists found that the P53 gene in bats, along with an accompanying gene, MDM2, had a unique mutation that could determine where the genes would be located in the cell. No other species had that.
"It's extraordinary that only bats have these unique changes out of all the animals we looked at and these particular genes are so important in pathways we know are really relevant in aging and a large range of viruses," Cowled said.
Bats are the only mammals that fly and they live a long time compared to other mammals of similar size. According to a study (PDF) from the University of Maryland, on average, the maximum recorded life span of a bat is 3.5 times greater than a non-flying placental mammal of roughly the same size.
Some fruit bats can fly hundreds of miles a night, expending vast amounts of energy. The energy generated can create free radicals which damage DNA. But Cowled said the scientists found that the bats had a unique ability to repair the damage. "They're either repairing the damage or blocking the worst case consequences,'' he said. The researchers believe this DNA-repairing capability relates to the bats evolving into flying creatures.
"Flying is a very energy intensive activity that produces toxic by-products but we can see that bats have some novel genes to deal with these toxins," he said. "What we found intriguing was that some of these genes also have secondary roles in the immune system. We're proposing that the evolution of flight led to a sort of spill over effect, influencing not only the immune system, but also things like aging and cancer."
Cowled pointed out that bats had evolved over millions of years. "They've been around since the time of the dinosaurs, at least 65 million years, and they're among the most abundant and widespread mammals on the earth. The bat genome holds over two billion pieces of information. Looking at it one piece at a time could take decades to find the right piece. By looking at the whole genome at once, we were able to focus on things that could one day give us new ways to combat infectious diseases, aging and cancer."
"We know they are producing high levels of toxic metabolic by-products, so when we discovered a concentration of evolutionary changes in the main pathway that deals with DNA damage, that to us was very suggestive of the types of adaptation that must have happened during the evolution of flight. The fact that those same genes are also involved in aging, anti-viral immunity and tumor genesis was really important."
The next step for the researchers would be to develop a greater genetic understanding of the animal. That in turn could lead to more targeted research and treatment of human diseases. Cowled said the scientists would be looking at the function of the genes to see whether they behave differently.
He said the "ground-level research" could lead to further insights in the treatment of cancer, aging and infectious disease.
"The majority of new diseases in humans come from animals and the viruses that come from bats are the most deadly of all,'' Dr Cowled said. "The more we can learn about bats, the better chance we have of protecting humans from disease. Medical science is always looking for new ways to treat cancer and infectious diseases and we think bats may be able to show us completely new ways of tackling human disease."
The findings were published in the journal Science.
Source: CSIRO
