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Sea Cucumber Genome Imparts Insight on Genes Linked to Organ Regeneration

NEW YORK (GenomeWeb) – Researchers have sequenced the sea cucumber genome, gaining insight into its ability to regenerate its internal organs.

As they reported today in PLOS Biology, researchers led by the Chinese Academy of Sciences' Jianhai Xiang have sequenced the Japanese sea cucumber, Apostichopus japonicus. They homed in on genes that may account for the sea cucumber's soft body, as compared to spinier echinoderms, as well as ones that appear to enable it to regrow its organs.

"The sea cucumber is a particularly promising model animal for regenerative medicine," Xiang said in a statement.

The researchers relied on a combination of Illumina shotgun and Pacific Biosciences long-read sequencing to generate an A. japonicus assembly some 805 megabases in size. That covers some 91 percent of the genome size estimated through flow cytometry. They also developed models of 30,350 protein-coding genes, 93 percent of which were supported by transcriptomic data.

A phylogenetic analysis of the newly assembled A. japonicus genome and 17 other animals — from water fleas to crown-of-thorns starfish to people — placed the sea cucumber among the Echinodermata. This placement also supports the notion that Echinodermata and Hemichordata are sister groups, the researchers said, placing their separation at 533 million years ago, around the time of the Cambrian explosion.

They also uncovered more than 49,000 homologous gene families among these metazoans, including about 450 gene families shared by both sea cucumbers and the purple sea urchin. Some 13,000 sea cucumber genes, however, couldn't be placed with those found in the other animals the team analyzed.

Unlike other echinoderms like sea urchins and starfish that have calcareous endoskeletons, sea cucumbers are rather fleshy. Even so, the researchers found that sea cucumbers share many of the parts of the skeletogenic regulatory system with those other echinoderms. They did report, though, that instead of having 31 biomineralization genes like the purple sea urchin does, the sea cucumber only has seven. Transcriptome data likewise revealed that these biomineralization genes are highly expressed in the purple sea urchin from the larval to pupal stages, while they are less abundant at those developmental stages in sea cucumbers.

Most interesting to the researchers from the standpoint of regenerative medicine studies was the sea cucumber's ability to spew out its viscera, which it does to scare off predators, and to then regrow them in a matter of weeks.

In this study, Xiang and his colleagues uncovered a cluster of tandemly duplicated genes that are very highly upregulated in sea cucumbers undergoing organ regeneration. These genes had no homologs in other species and encoded proteins that harbored conserved cysteine residues, suggesting to the researchers that they belong to an A. japonicus-specific gene family. Further protein analysis indicated that they also included a domain similar to that of PSP94, leading the researchers to call them PSP94-like genes.

The researchers similarly noted that a cluster of 21 tandem duplicated FREP genes were active during organ regeneration.

Additionally, they found that A. japonicus harbored orthologs of mammalian pluripotency factors like Sox2, c-Myc, Oct4, and Klf4, some of which were upregulated shortly after the sea cucumbers shed their viscera. This further hinted to the researchers that regenerative mechanisms in sea cucumbers have similarities to those of vertebrates.

"This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications," the authors wrote.