An international team of researchers has sequenced the genome of the elephant shark, a curious-looking fish with a snout（鼻子） that resembles the end of an elephant's trunk. The elephant shark and its cousins the sharks, rays, skates and chimaeras are the world's oldest-living jawed¹ vertebrates. But their skeletons are made of cartilage rather than bone, making this group of vertebrates an oddity（古怪） on the evolutionary² tree.

 

Now, by comparing the genome of the elephant shark with human and other vertebrate genomes, researchers at Washington University School of Medicine in St. Louis and elsewhere have discovered why the skeleton of sharks is cartilaginous（软骨的）. An analysis of the creature's genome, published Jan. 9 in the journal Nature, offers new insights into the genetic³ basis of bone formation and the molecular⁵ origins of adaptive immunity⁶, which provides organisms with a more sophisticated immune response to pathogens.

 

Collectively, the findings have important implications for understanding bone diseases such as osteoporosis and for developing more effective therapies to treat these conditions. Findings related to the elephant shark's immune system provide new opportunities for studying adaptive immunity in humans and for formulating⁷ new strategies to fine-tune the immune response.

 

"We now have the genetic blueprint⁸ of a species that is considered a critical outlier for understanding the evolution and diversity of bony vertebrates, including humans," said senior author Wesley Warren, PhD, research associate professor of genetics at The Genome Institute at Washington University School of Medicine. "Although cartilaginous vertebrates and bony vertebrates diverged⁹ about 450 million years ago, with the elephant shark genome in hand, we can begin to identify key genetic adaptations in the evolutionary tree."

 

Among the cartilaginous fishes, the elephant shark was selected for sequencing because of its compact genome, which is one-third the size of the human genome. The fish lives in the waters off the southern coast of Australia and New Zealand, at depths of 200 to 500 meters, and uses its snout to dig for crustaceans¹⁰ at the bottom of the ocean floor.

 

By analyzing¹¹ the elephant shark genome and comparing it with other genomes, the scientists discovered a family of genes¹² that is absent in the elephant shark but present in all bony vertebrates, including the chicken, cow, mouse and human. When the researchers deleted a member of this gene⁴ family in zebrafish, they observed a reduction in bone formation, highlighting the gene family's significance in making bone.

 

In a surprise finding, the team found that the elephant shark appears to lack special types of immune cells that are essential to mounting a defense¹³ against viral and bacterial¹⁴ infections and for preventing autoimmune diseases such as diabetes¹⁵ and rheumatoid arthritis¹⁶（风湿性关节炎）.

 

However, despite possessing a relatively¹⁷ rudimentary immune system, sharks exhibit robust¹⁸ immune responses and live long lives. The new discovery opens up the possibility of developing new strategies to shape the immune response in humans.

 

The researchers also determined¹⁹ that the elephant shark genome is the slowest-evolving among all vertebrates, including the coelacanth, a prehistoric²⁰ fish popularly known as a "living fossil."

 

Furthermore, large chunks²¹ of elephant shark and human chromosomes²² were found to be highly similar, whereas the corresponding regions in fishes such as zebrafish and pufferfish（鸡泡鱼） were fragmented and scattered²³ on different chromosomes. The markedly slow-evolving feature of the elephant shark genome further underscores its importance as a reference genome for studies aimed at better understanding the human genome.

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