By sequencing the elephant shark genome, researchers have gained a window not only into the genetic basis of bone formation, but the molecular origins of adaptive immunity - a key to a more sophisticated immune response to pathogens.
The elephant shark was selected because of its compact genome, which is one-third the size of a human's. By comparing it to other genomes, the researchers identified a family of genes lacking in the elephant shark but present in all bony vertebrates. Notably, when one of the members of the gene family was deleted in zebrafish, the animal saw a reduction in bone formation, according to the study published in the journal Nature.
"We now have the genetic blueprint of a species that is considered a critical outlier for understanding the evolution and diversity of bony vertebrates, including humans," Wesley Warren, a research associate professor of genetics at The Genome Institute of Washington School of Medicine. "Although cartilaginous vertebrates and bony vertebrates diverged about 450 million years ago, with the elephant shark genome in hand, we can begin to identify key genetic adaptations in the evolutionary tree."
The researchers were surprised to find that the shark does not possess special types of immune cells used to fight viral and bacterial infections and prevent autoimmune disease like diabetes and rheumatoid arthritis. This was unexpected given that sharks have a particularly strong immune response.
The findings, according to the researchers, could have major implications for understanding and developing treatments for bone diseases, such as osteoporosis, as well as for new strategies to shape the human immune response. They also revealed that the elephant shark is the slowest-evolving among all vertebrates.
"The slow-evolving genome of the elephant shark is probably the best proxy for the ancestor of all jawed vertebrates that became extinct a long time ago," said lead author Byrappa Venkatesh, the research director at the Institute of Molecular and Cell Biology at the Agency for Science, Technology and Research. "It is a cornerstone for improving our understanding of the development and physiology of human and other vertebrates as illustrated by our analysis of the skeletal system and immune system genes."
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