The Christmas Island rat was abundant when Captain John Maclear anchored his ship Flying Fish in a bay off the Indian Ocean Island in 1887. His crew made a small collection of local fauna, among them the first specimen of the indigenous rat species. Phosphate mining operations began shortly thereafter on the Island, and the rats were not recorded again after 1905. Christmas Island rats were considered to be completely extinct by 1908, due to the accidental introduction of black rats (R. rattus) infested with fleas that carried the fatal disease typanosomiasis.
Having been extinct for just over 110 years, and with several museum specimens preserved for posterity, the Christmas Island rat makes an interesting candidate for de-extinction. This is a process whereby lost species are resurrected using one of several possible biotechnologies. In this case, a team of paleogeneticists considered the possibility of using genome editing to reconstruct the entire genome of the extinct rat species. Their findings are published today in the journal Current Biology, where they assess the chances of success and the limitations of this approach.
Usually, when sequencing the genome of an extinct species, scientists face the problem of fragmented and degraded DNA that does not reveal all the genetic information needed to reconstruct the entire genome. However, with the Christmas Island rat, evolutionary geneticist Tom Gilbert from the University of Copenhagen and his colleagues were able to obtain almost all of the rodent’s genome from the specimens housed in museums in the UK. In addition, since this species diverged relatively recently from other Rattus species that are still extant, it shares about 95 percent of its genome with living Norway brown rats.
“It was a quite a nice test model,” says Gilbert. “It’s the perfect case because when you sequence the genome, you have to compare it to a really good modern reference.”
Once the DNA of the extinct species had been sequenced, it was matched up with the genome of the living species for reference. This enabled the scientists to identify any parts of the extinct species’ genome that were missing. Indeed, they found that a few key genes were missing. These genes were related to olfaction in Christmas Island rats, meaning that a resurrected rat would likely be unable to process smells in the way it would originally have done.
In theory, CRISPR gene editing technology can be used to edit the DNA of the living species so that it matches that of the extinct species. If this was done on germ cells (sperm or ova) of brown rats, then they could become parents of offspring that contained the extinct species’ genome. However, this technology cannot be successful if there are missing genes that are unique to the extinct species. Unfortunately, the more degraded and old the tissue from the extinct species is, the more fragmented the resulting DNA will be, making genome assembly more challenging.
“With current technology, it may be completely impossible to ever recover the full sequence, and therefore it is impossible to ever generate a perfect replica of the Christmas Island rat,” said Gilbert.
This scenario is particularly pertinent to attempts to resurrect mammoths, which went extinct several thousand years ago. Although modern elephants are genetically similar to mammoths, the mammoth DNA has had thousands of years of degradation and will not contain a complete set of functional mammoth genes in the genome.
“It is very, very clear that we are never going to be able to get all the information to create a perfect recovered form of an extinct species,” said Gilbert. “There will always be some kind of hybrid.” Though a replica will never be perfect, the key is that scientists are able to edit for the DNA that makes the extinct animal functionally different from the living one.
Gilbert explained that in order to make an ecologically functional mammoth, for example, it might be enough to edit elephant DNA to make the animal hairy and able to live in the cold. “If you’re making a weird fuzzy elephant to live in a zoo, it probably doesn’t matter if it is missing some behavioral genes. But that brings up a whole lot of ethical questions.”
Gilbert plans to perform the actual gene editing on rats, but would like to start with species that are still living. He intends to begin by performing CRISPR edits on a black rat genome to change it to a Norway brown rat genome before attempting to resurrect the Christmas Island rat.
Though he is excited about this future research, the whole process still poses ethical questions. “I think it’s a fascinating idea in technology, but one has to wonder if that’s the best use of money as opposed to keeping the things alive that are still here.”