As mist lingers over a Swedish fjord lined with towering, forested cliffs, a group of scientists collect mud from the bottom of the turquoise-colored waters. Theyâ€re after brittle stars—marine animals with long, slender, serpent-like arms—to peek into the genes that give them distinct characteristics, including the power of regeneration.
Brittle stars belong to the phylum Echinodermata, which includes sea stars, sea urchins, sea cucumbers, and sea lilies. While the genomes of these other echinoderm classes have been characterized, Ferdinand Marlétaz, an evolutionary biologist at University College London, noted, “Surprisingly, there was no genome available [for brittle stars].â€1-4
To study this intriguing creature, Marlétazâ€s team collected hundreds of brittle stars from a fjord in Sweden and returned to the lab to sequence the genome of the marine animal, which belongs to the species Amphiura filiformis.5 The results, published in Nature Ecology & Evolution, shed light on how animals in the Amphiuridae family have evolved, and provide insights into the genes involved in limb regeneration.
“This is a huge resource,†said Mansi Srivastava, an evolutionary developmental biologist at Harvard University who was not involved in the study. “It’s going to advance questions that many people in evolutionary developmental biology are asking.â€
Marlétazâ€s team extracted and sequenced the DNA they collected from the brittle stars and assembled the genome. To map how brittle stars have evolved since they diverged from other echinoderms about 500 million years ago, the team compared the A. filiformis genome with those of sea urchins, sea stars, and sea cucumbers. They observed that the brittle star genome had undergone more major genetic changes, such as shuffling of genes across chromosomes, relative to the other echinoderms. Among the rearranged genes were those in the Hox cluster, which shape the animalâ€s body plan. These genes occur in the same order on the same chromosome across evolutionarily distant animals.6 While genes in the Hox cluster of other echinoderm classes showed this expected order, those in the brittle star genome broke this pattern.
“[This was] striking, because we know that the Hox cluster is very conservative in terms of gene order,†said Elise Parey, an evolutionary biologist at University College London and a study coauthor.
Srivastava noted that studying this rearrangement can provide important insights about the role of this gene cluster in echinoderms. “Hox genes seem to have a lot of constraint across evolution,†said Srivastava. “Now here’s an animal that has played with that constraint. So, studying something that deviates from the rules can actually tell you something more about the rules,†she explained.
With the brittle star genome in hand, Marlétaz and his team investigated another important feature of the animal: their ability to regenerate. Like many other echinoderms, brittle stars can regenerate their limbs following amputation.7 “The brittle star can regenerate the arm in just a month, which is very, very fast,†said Parey. In comparison, sea stars take up to a few months to regrow a lost arm, making brittle stars an important model to study genes involved in regeneration.
Marlétaz and his team sought to identify the genes that underlie such regenerative powers. They cut the arms off almost 3,500 animals and assessed gene expression as the arms regrew. As regeneration progressed, different genes emerged as important mediators. Genes involved in wound response, including immunity- and cell migration-related functions, are activated during the early phases of regeneration while later stages are marked by increased activity of genes associated with tissue differentiation and limb shaping.
Mapping the ancestry of these genes revealed that arm regeneration largely involved the expression of ancient genes, indicating shared genetic roots between other regenerating animals. To investigate whether similar genes were involved in regenerating limbs in other animals, the team looked at the genes expressed during regeneration across distantly related species. They compared their brittle star gene profiles with previously published data from two other regenerative animals—axolotls (Ambystoma mexicanum) and marine crustaceans (Parhyale hawaiensis). They observed that all three animals expressed similar genes during limb regeneration, validating a shared ancestral origin for regeneration.
“Our paper is probably one of the few that tried to compare the genes that are involved in regenerative process across lineages,†said Marlétaz.
“This is a paper thatâ€s a call for us to study more species in this comparative way,†agreed Srivastava. However, according to her, identifying genes in brittle stars is a first step. “To actually ask what they are doing, you have to do functional work at the bench.â€
Paray agreed. “The [next steps] would be biological validation experiments to dissect the role of a given gene.â€
