Lineus longissimus is not only long, it is also extremely slimy. The toxic mucus of nemertean worms was first described in 1555 by Swedish archbishop and naturalist, Olaus Magnus. Despite his work detailing giants, unicorns, and sea monsters, researchers think he was describing Lineus longissimus when he wrote, “The worm is entirely harmless, unless touched by a human hand. In that case, the fingers will swell when the animal comes into contact with the skin of the hand”.1
In the 1960s researchers started to define toxins in the mucus of a range of nemertean species. Many are neurotoxins that affect a wide range of animals and may function to defend the worms from predators.
It was not until 2018 that toxins from Lineus longissimus mucus were extracted and fully described2, when Swedish researchers characterised α-nemertide toxins. These paralyse and kill green crabs by affecting sodium channels in the crab nervous system. Because the toxins also kill cockroaches, but have limited effects on mammalian cells, they are potential new insecticides.
An early illustration of a ribbon worm (possibly L. longissimus) is seen in William Borlase’s Natural History of Cornwall (1758). It was denoted a “Sea long worm” and then categorized as belonging to the “less perfect kind of sea-animals”. (Image and caption from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410017/#B29-toxins-11-00120 Licence: https://creativecommons.org/licenses/by/4.0/)
The toxins characterised in the 2018 study came from just 17 species of nemertean. Thousands of other chemicals have been identified from a relatively small number of marine plants, animals, and microbes. There are likely to be many more, waiting to be discovered. Several compounds have been successfully developed by the pharmaceutical industry – drugs to treat leukaemia and HIV were based on findings in sea sponges3.
And looking beyond the oceans, almost a third of all small-molecule drugs approved by the U.S. Food and Drug Administration between 1981 and 2014 were either natural products or compounds derived from natural products.4 With an estimated 90 per cent of eukaryotic species on Earth yet to be discovered5, there is huge potential to uncover new anti-fungal, anti-bacterial or anti-viral compounds.
Working with worms
The sample of Lineus longissimus was collected by Sanger Institute staff on the island of Cumbrae in Scotland, during a field trip based at the Field Studies Council Millport centre6. It was found tangled in the holdfast of seaweeds in the intertidal zone. Described as a ‘relative tiddler’ at a resting length of 20 cm, the specimen did reach about a metre when questing around its tank, secreting mucus all the while. It was formally identified then snap frozen in liquid nitrogen to preserve it, and shipped to the Tree of Life laboratory at the Sanger Institute. Other marine species in the Darwin Tree of Life project will come from a range of partner organisations, including the Marine Biological Association, who have a major role in sampling aquatic species - from phytoplankton to fish.
The Sanger team collecting samples on Cumbrae, Scotland. Image credit: Mark Blaxter
Caroline Howard, lead at the Tree of Life lab at the Sanger Institute, commented on the difficulties of working with Lineus longissimus. “No-one had attempted a nemertean genome before. Getting DNA out of a worm that makes so much slime was a challenge, but we were able to use techniques we had been using on snails to do a good job. Now we’ve done one nemertean species, we can build a system to do the many others.”
The genome was deciphered using the Sanger Institute’s new fleet of long-read sequencers. Scientists and bioinformaticians analysed the data to determine the genome sequence of Lineus longissimus and the sequencing data have been released openly for anyone to use. Importantly, the resulting genome has been reconstructed as whole chromosomes, and is effectively complete. This means that researchers studying the toxins, and other features of this active predator, can be sure that they have all the information they need for their work.
“Collecting species for the Darwin Tree of Life project is helping us understand the biodiversity on our shores and in our waters. It’s a huge collaborative effort, including researchers and naturalists with expertise in a range of areas,” said Patrick.
Mark Blaxter, Head of the Tree of Life Programme at the Sanger Institute, said: “The genome sequences of animals like Lineus longissimus will aid a whole new generation of research – including the discovery of new active molecules for medicine and other applications. There are many groups of creatures, like nemerteans, where we know very little beyond the fact that they exist, and the Tree of Life genomics programme aims to use genomes to understand each and every one.”