Inside Stories

What’s in a genome?

SOSF Shark Research Center

Mahmood Shivji

Words by Mahmood Shivji

As part of the Shark Research Center’s ongoing work in the field of comparative genomics of sharks, the complete set of white shark Carcharodon carcharias genes – known as the genome – have been sequenced and the findings were published in the journal Proceedings of the National Academy of Sciences. The research paper, titled ‘White shark genome reveals ancient elasmobranch adaptations associated with wound healing and the maintenance of genome stability’, gives new insights into why sharks are so well adapted to their environment, why they are able to heal quickly from wounds and why they seem to suffer less than humans do from age-related diseases and cancers. The paper’s lead author, Nicholas Marra, worked with a host of co-authors to look at how the white shark has been adapted right from the molecular level of its DNA to its ocean environment. This work forms part of a much bigger body of research that we are still conducting – and a busy year it appears lined up to be!

Our current focus lies in three areas. Firstly, we’re interested in the conservation genetics of sharks, which involves identifying genetically unique elasmobranch populations and understanding their dynamics, deciphering elasmobranch breeding behaviour and developing genetic tools to investigate the trade in shark body parts. All this research contributes to how we better manage dwindling or threatened shark populations, using a host of genetic tools as a way to add to the current arsenal of scientific methods.

Secondly, we are investigating comparative genomics, which involves studying how elasmobranchs function at their most fundamental biological level; that is, their whole genomes, especially with regard to the genetic basis of their ability to heal from wounds efficiently and their apparent higher resistance to cancers. The white shark study formed part of this line of investigation. Lastly, we’re looking into the movement ecology of sharks, which is the study of shark migration patterns and their interaction with commercial fishing.

Follow-up genomics research for this year includes digging deeper into the genome sequences of the white shark to gain more insight into its population trends, as well as advancing our work on assembling and characterising the genome of the endangered great hammerhead shark. This research is an extension of the previous work we did on sequencing a subset of white and great hammerhead shark genomes; that is, the transcriptomes, which represent only the sequences of the shark genes that are expressed.

Mahmood Shivji Director of the SOSF Shark Research Center

A white shark skirts the edge of a shoal of fish off the coast of Massachusetts.
Photo by Brian J. Skerry | National Geographic Image Collection

The publication of the white shark’s entire collection of genes is interesting to us at the SOSF Shark Research Center for several notable features in white shark biology that are particularly illuminating and were revealed by sequencing the species’ entire genome. Given the word limits for scientific journals, when it came to writing our paper we focused on reporting three unexpected, but major findings.

Firstly, the white shark genome is large – 1.5 times the size of the human genome, in fact! We believe this is, in part, the result of a high proportion of a particular type of DNA sequence motif known as LINEs. These LINEs (also known as ‘jumping genes’) are prone to making copies of themselves and then inserting the copies in various places around the genome, which requires first breaking the DNA at the insertion site. Although such breaks are fixed, mistakes do occur in the fixing process, resulting in the genome becoming unstable. This genome instability is well known to cause diseases (such as cancers) in vertebrates (including humans), which have been well studied at the genome level. The finding of such a high proportion of LINEs in the white shark raises the question, did their genomes have a higher susceptibility to becoming unstable?

Our second major finding is related to this genome instability issue and is also unexpected but quite interesting. The white shark has a large number of genes involved in the maintenance of genome stability that have undergone a type of natural selection known as ‘positive selection’. This selection can be thought of as changes in the gene sequence that confer biological advantages. Notably, many of these positively selected genes are involved in repairing sequence mistakes in the DNA and suppressing tumour formation. This finding suggests that the white shark has evolved superior genetic abilities to keep its genomes stable, despite the fact that it has such a large proportion of LINEs.

Finally, the third novel finding we focused on was that several genes known to play key roles in vertebrate wound healing pathways have also undergone positive selection. This finding fits in nicely with the well-known observation that sharks can heal from wounds quite quickly. The positive selection in woundhealing genes could explain the genetic basis underlying the efficient wound healing observed in sharks.

Sharks in general represent an ancient vertebrate lineage. Their evolutionary success probably stems from having acquired key adaptations to their environment, including the ones we found by decoding the white shark genome and analysing the whale shark genome. We have just scratched the surface when it comes to discovering how finely tuned sharks are to their complex, three-dimensional environments. I’m sure we will discover many more novel adaptations as we dig further into the genome and specific genes and their functions. These findings highlight what evolutionary marvels sharks are and provide yet another compelling and urgent reason to conserve these animals before we lose them to overfishing.

A white shark skirts the edge of a shoal of fish off the coast of Massachusetts.
Photo by Brian J. Skerry | National Geographic Image Collection