Rotifers are ancient asexual oddities: these tiny freshwater animals have survived for an estimated 1,000 years or more without sex and the evolutionary advantages that it provides. 25 million yearsA new study reveals how this resilient lineage of aquatic organisms managed to survive for so long and spread across the globe, from damp moss to Antarctic ice sheets, without sexual gene exchange. Curiously, the discovery could help scientists target better antibiotic treatments for humans.
The tiny, multicellular aquatic rotifers likely manufacture their own antibiotics using genetic material stolen from plants, fungi and bacteria. the study Published in the Journal on July 18th Nature CommunicationsBy stealing genes from non-animals, rotifers can produce compounds that are not normally available to them. The results suggest that the borrowed genes help some rotifers survive infection with a virulent fungal pathogen, complementing the standard animal immune system.
“We never thought that animals could make these chemicals,” says Chris Wilson, a biologist at the University of Oxford in the UK and lead author of the study. “Bacteria and fungi are really good at this. [type of] “Humans are chemists. Animals aren’t.” But among the many rotifer gene sequences that Wislon and his colleagues examined, they found instructions for building miniature antibiotic factories—basically recipes stolen from bacterial and fungal cookbooks.
Not having sex
Genetic exchange through sexual reproduction is one of the main ways multicellular organisms evolve resistance to diseases: by mixing and sharing genetic information from generation to generation, animals are more likely to encounter particularly beneficial combinations. But in centuries of observation, scientists have never found a male rotifer, suggesting that the microscopic animals reproduce exclusively by parthenogenesis.
The phenomenon of reproducing without fertilization is well documented among animals, from insects to reptiles to birds. But it is usually rare and most often combined with bouts of sexual reproduction, and pure parthenogenetic species tend not to stand the test of evolutionary time. Rotifers defy all three of these trends, making their success a long-standing mystery. The new discovery helps to solve this mystery.
Previous genetic studies have demonstrated that rotifers possess large amounts of DNA of non-animal origin. About 11 percent Most of their genomes were brought over from elsewhere through a process called “horizontal gene transfer,” usually via viruses, but this is the first time that a horizontally acquired gene has been linked to survival of the infection.
The rate of horizontal gene transfer in rotifers is still much lower than the evolutionary rate in sexually reproducing species, but the study suggests that even these slowly acquired bits of DNA may be important for rotifers’ evolutionary durability.
“It’s becoming increasingly understood that horizontal gene transfer is rare. [animals]”It’s certainly happening, and it seems to have an effect,” says Maria Rosa Domingo Sananes, a microbiologist at Nottingham Trent University in the UK, who was not involved in the new study. She says the work sheds light on the functional mystery of what these genes do. “There are always questions like, ‘Is it genetic drift?’, ‘Is it genetic parasitism?’, ‘Is it actually beneficial?’ and this is a first step towards the answers.”
Tracking genetic contraband
To figure out the purpose of the plundered rotifer genes, the scientists first had to make the rotifers sick. They exposed two strains of rotifers to a particularly nasty fungal infection. The Last of UsWilson says Popular Science. “If the rotifers are successfully infected, they will eventually explode into a mass of bacteria. Not a very good ending.”
One Bedelloid species was highly susceptible to the fungus, with over 70% mortality after three days, while the other was much more resistant, with only 18% dying in the same period.
The biologists tracked gene expression throughout the course of disease in each species. They found that in both lineages, exposure to the pathogen activated a disproportionate number of the stolen gene sequences — 23 to 32 percent of all expressed genes. There was a lot of overlap among these activated sequences. But in the resistant species, a set of genes that catalyzes the formation of antibacterial chemicals in the bacteria was overactive, 10 times more so than in the susceptible species.
“This really caught our eye, and when we looked at how the genes worked, this was the clearest pattern,” Wilson says. “Putting these two facts together, we suggested that these genes are one of the main defenses that rotifers have against this pathogen.”
The researchers modeled what the specific products of these cellular chemical factories might be and predicted that the final compounds would resemble known, powerful, broad-spectrum antibiotics and antifungals. Although the rotifers made some tweaks to their genes and the sequences were not an exact match for non-animal sources, their utility would likely be similar.
Solution to illness
Antibiotic resistance is a growing problem as more microbes evolve to evade the drugs we rely on, but finding new, reliable antibacterial drugs is hard, Wilson notes: Many of the compounds that kill pathogens have also been found to harm human cells.
Discovering drugs made by rotifers could be useful. Because rotifers are animals, the compounds they make have to be at least tolerable to animals. “They can’t be too toxic, otherwise they can’t make the compounds in their own cells,” Wilson says. “We think rotifers might be a useful lead, or a shortcut, in the search for human-compatible antibacterial chemicals.”
“It’s an interesting idea and a good discussion,” agrees Domingo Sananes. When it comes to antibiotic resistance, “we need to try everything we can,” he says. “If there’s underutilized diversity in these rotifers, why not explore it?”
But just because rotifers can tolerate a compound doesn’t mean it will work in humans: Mice are much more closely related to humans than rotifers are to humans, she points out, and treatments that prove safe and effective in rodents often don’t meet the same standards in human clinical trials.
Both Wilson and Domingo-Sananes caution that much more research is needed before this work can be translated into humans. The next big step will be to actually isolate the chemicals produced by the disease-resistant rotifers and confirm that the compounds are antibacterial. Domingo-Sananes also wants to do follow-up studies evaluating other rotifer strains and pathogens to see if different types of infections trigger different genetic responses.
For now, Wilson remains pleasantly surprised and optimistic. And, at the very least, he sees his discovery as a reason to keep exploring strange biology. “When I started this research, I never thought there’d be any relevance to antibacterials,” he says. “It’s one of those things that just happens to be discovered by chance, in the same way that antibiotics themselves were discovered by chance in the first place.”
“If you take a good look at the totally unknown – the tiny animals that live in the soil that nobody has ever heard of – you might find something unexpectedly useful.”
