Olm genome analyses to step up medical breakthroughs
Ljubljana, 14 October - Due to its unusual characteristics the olm has been the subject of research for more than 100 years. There is great biomedical potential waiting to be unlocked through researching the amphibian's longevity, its ability to regenerate and other survival mechanisms, argues biologist Rok Kostanjšek, who has been analysing the animal's genome.
The olm or Proteus anguinus is endemic to the Dinaric karst region. Its home is the underground waters of a vast area that spans from the Soča estuary near Trieste, Italy, all the way to Montenegro. In Slovenia, it can be found in caves in the south.
Its natural habitat is an area of the greatest underground biodiversity in the world that is in the league of coral reefs or tropical rainforests, Kostanjšek, an expert from the Ljubljana Biotechnical Faculty, told the Slovenian Press Agency.
"The olm is an umbrella predator, which means that its presence shows that there is enough food for it, that the whole ecosystem is stable, and that the water in which it is found is drinkable." It is no wonder then that the olm has been dubbed the guardian of underground drinking water.
Extreme living conditions in caves have led the amphibian to develop unique characteristics and adaptations to the subterranean environment.
It is pale-skinned, with eyes that are covered with skin, as they serve no purpose in the dark environment. As a result its sense of smell and sensory organs are much more developed.
Modern research has identified some additional features of the largest cave vertebrate, such as exceptional longevity, an interesting ability to starve and an extreme ability to regenerate.
"For example, it can survive without food for many years and reach an enviable age of over 100 years, with the ability to reproduce in its 80s. It also has, same as some other tailed amphibians, the ability to regenerate damaged organs and tissue without scarring."
Project analysing olm genome
Precisely because of the olm's unusual and extraordinary characteristics the Biotechnical Faculty launched together with the Danish Aarhus University and the Chinese institute BGI Research a project in 2020 to identify its genome to gain a better understanding of the animal's features.
Funded by the Slovenian research and innovation agency, the project Genomic and Transcriptomic Insights into the Unique Biology of Proteus ended in late August.
"The genome has been analysed and its pieces put together to a large extent; all that is missing is a few final analyses," Kostanjšek said.
There were some challenges during the research, he noted, a key obstacle being the sheer size of the genome and the limited availability of analysis equipment during the Covid pandemic.
"Like other tailed amphibians, the olm has an extremely large genome, roughly estimated to be 15 times larger than the human genome, which meant a huge amount of data had to be processed," he explained.
They found that the genome is so large because it contains repetitive sequences that carry no genetic information, but merely act as a kind of a filler.
"Similarly, the human genome has a huge amount of non-coding parts, the biological role of which is not yet fully understood," he said. The amount of genes in the olm is comparable to other eukaryotes.
According to the biologist, research of such large genomes could provide answers to key questions in biology, such as why a significant part of the human genome contains non-coding regions or what their biological function is.
The olm's unusual features and their great biomedical potential
The findings about the unusual characteristics of the olm could be transferred to the field of human medicine.
Kostanjšek highlights the potential of the animal's unusual longevity. "The amphibian is extremely long-lived given its small size, which is an interesting peculiarity. Large organisms, such as turtles, elephants and humans too, are known to be long-lived.
"Small animals, on the other hand, are generally short-lived, but the olm has a lifespan comparable to men's despite its small size," he said.
Since the olm's amphibian relatives are short-lived, comparisons of their genomes are needed in the future. This will help scientists to identify where the differences in longevity genes are, and to identify which genes are more important for longevity.
By confirming their presence in humans, they would then be able to identify key genes among the known longevity-related genes and focus research on them.
"However, we need to be aware that identifying these genes alone will not answer the question of why certain organisms, including humans, are long-lived. This depends on a wider set of circumstances, such as lifestyle and the organism's state of health."
Another fascinating feature worth looking into is the regeneration ability.
By learning about the olm's mechanisms of effective regeneration scientists are not going to make human arms grow back, but it will help them better understand and improve healing processes and reduce a hospital stay after surgery.
By unravelling the mystery of the genome, they will also be able to better understand how the olm manages to survive years of starvation and then overeating without any negative effects on the organism.
Getting to know the amphibian's metabolic processes could also have great biomedical potential, Kostanjšek said.
"In humans, starvation leads to anorexia, and intense feeding after starvation triggers insulin intolerance, which leads to diabetes, whereas this does not happen in the olm," he explained.
The findings could therefore also make an important contribution to better understanding the origins of diseases such as diabetes and provide more effective treatment.
Proteus remains a mystery
Even though at first glance it might seem that people know a lot about the olm, there are still a lot of things shrouded in mystery.
"We still don't known enough about this extraordinary animal. We've found it in Slovenia, we used to have its image on coins, we issue stamps dedicated to it, but we don't know where exactly it lives and how many of them are out there, what is the population composition, and we cannot, for example, determine its sex as it is usually indeterminable based on external features and chromosome patterns.
"As a result we do not have a national strategy to protect this cave amphibian and its natural habitat, and for now we do not know how to breed them in a controlled way in laboratory conditions. We also do not know their threat level or to what extent they are threatened by agricultural fertilisers, other pollutants and the loss of habitat."
It is precisely these gaps in knowledge that are a great challenge in olm protection and research plans, Kostanjšek said.
Genome analyses will help answer these questions. "Nothing is simple when it comes to the olm. Any finding, no matter how tiny, is a step closer and that is why research in this area is of the utmost importance and will continue. Analysing the olm's genome is just the first step on this path."