About this episode
The genetic secrets to extraordinary longevity, superhero-like healing and regeneration, and resistance to feeding disorders could be found hidden within the Earth. In underground caves in Dinaric Karst along the Adriatic Sea in the Western Balkans lives a cave salamander, the olm, whose remarkable adaptations mean its genome holds great promise for biomedical research. Dr Rok Kostanjšek and an international team of scientists at the Proteus Genome Research Consortium are tackling the challenge of sequencing the huge olm genome, to provide the basis for studying its unique genetic characteristics. More
Underground cave systems are a hostile and challenging environment. Animals calling these caves home must cope with constant darkness, chronic food scarcity, high humidity, and sometimes even a lack of oxygen.
It is little wonder that animals evolving to survive in these strange environments take on an alien appearance. A set of characteristic cave traits – called ‘troglomorphisms’ – are shared by most cave species. The olm – a cave-dwelling salamander whose natural populations can be found exclusively in Dinaric Karst in the Western Balkans – lost its eyes over more than 10 million years of perpetual darkness. Many other senses compensate for its blindness, such enhanced smell, taste, touch, and hearing, as well as the ability to sense electric currents and magnetic fields, and perceive the tiniest amounts of light with their skin cells.
The olm’s head and body have become bizarrely elongated. Its skin is pale – almost translucent. To survive the chronic food shortages of caves, the olm has a metabolism that can withstand up to eight years of starvation.
Additionally, olms possess some characteristics associated with their salamander heritage. Like their cousin – the axolotl – which are popular pets, olms retain their juvenile form throughout their very long lives. Olms may live for over 100 years, making them among the longest living animals known to science and the longest living amphibian by decades. Like other members of the salamander group, olms can fully regenerate damaged limbs and organs.
These remarkable abilities are encoded into its genome. By sequencing the enormous genomes of olms – comparable in size to the largest animal genomes ever sequenced – scientists at the Proteus Genome Research Consortium aim to provide the basis for effective protection of this endangered species. This knowledge would also advance biomedical research that could help us to live longer, heal faster, regenerate damaged body-parts, and potentially prevent metabolic and feeding disorders such as obesity, anorexia and diabetes.
Dr Rok Kostanjšek and Dr Nina Gunde-Cimerman from the University of Ljubljana coordinate the Slovenian part of this international consortium of genetics experts from Slovenia, Denmark, Germany and China, who are undertaking the immense task of deciphering the olm genome.
The scientists are using a combination of advanced tools and techniques to overcome the technical challenges of sequencing such a large genome. This approach has been used to successfully sequence other extremely large animal genomes, such as those of the lungfish and axolotl.
The newer techniques available may allow the team to investigate another mysterious characteristic of the olm’s genome. Like some other animals, the olm genome has large sections of repeating DNA sequences. Older genetic tools struggled to identify these repetitive sections of DNA. However, newer technologies can accurately determine the quantity and sequences of repetitive DNA within the genome. Theories suggest that rather than being redundant sections without any function, repetitive DNA could help other genes to function, provide structural integrity to the genome, and may be involved in the evolution of new traits.
Studying the olm genome requires access to high-quality tissue samples for obtaining DNA. However, because olm populations are highly vulnerable due to loss of their habitat, the team must pay special attention to sourcing their samples ethically to prevent any further impact on this endangered species. Olms are highly protected by both European Union legislation and national laws in Slovenia, where the sample population lives. This population was chosen in large part because it is stable, healthy, and resilient.
Once sequenced, the olm genes responsible for its remarkable characteristics can be determined. Identifying new genes takes place over a multi-stage process. First, the olm genome will be compared to other sequenced genomes. Regions of similar DNA could point towards genes that encode similar traits in different species, such as skin colouration, eye development and common mechanisms behind adaptation to cave environments. Then, focusing on coding regions within the remaining DNA could help the team to narrow down the search for novel genes.
This method of comparing known genes with unfamiliar genetic sequences has led to many important historical biomedical discoveries. For example, much progress towards understanding the genetic mechanisms behind resisting starvation and obesity has been made by studying the genome of cavefish. Cave species are capable of prolonged starvation, but can also feast when food is abundant without developing obesity or insulin resistance. The olm’s genome could also hold clues to how the human immune system functions during periods of starvation.
Studying the olm genome could provide an even better understanding of metabolic mechanisms, because it is more closely related to humans on the evolutionary tree than fish species. Since there are no fully cave-adapted mammals, the olm is arguably the most faithful mirror for some human medical conditions that share a genetic basis with cave traits.
Genes controlling loss of vision, skin pigmentation abnormalities, circadian rhythm disorders and a range of other medical conditions in humans provide the genetic basis for traits that are adaptive in the harsh underground environments.
But perhaps the most fascinating trait that may one day be harnessed in biomedicine is the extraordinary regenerative capabilities of salamanders. Olms, axolotls, and other salamander species can regrow fully functional limbs and organs that have been lost or damaged. Most of our understanding about the genetics behind this extraordinary ability are based on the axolotl genome. Investigating this ability in the olm genome could provide new insights that expand the possibility of applying the trait to biomedicine.
Perhaps the possibility of developing therapies to considerably shorten the healing process after surgeries or even regrow organs and limbs will not always be confined to the realms of science fiction.
Work on the olm genome by Dr Kostanjšek, Dr Gunde-Cimerman and their colleagues at the Proteus Genome Research Consortium could unlock the secrets for prolonging life, curing a range of medical conditions, and one day even regrowing limbs and organs.
Original Article Reference
This Audio is a summary of the paper ‘Toward the massive genome of Proteus anguinus – illuminating longevity, regeneration, convergent evolution, and metabolic disorders’, in Annals of the New York Academy of Sciences. doi.org/10.1111/nyas.14686
For further information, you can connect with Dr Rok Kostanjšek at [email protected]
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