Extinct rat shows limits of CRISPR to reviving species

Before the early 1900s, if it walked like a Christmas Island mouse and spoke like a Christmas Island mouse, it was likely a Christmas Island mouse. But if one of these now-extinct mice ever walked the earth again, it would in fact be a genetically modified Norwegian brown mouse. A new study has found that the rodents will not resemble a Christmas Island rat as some hope.

with advent Gene editing technology like CRISPRScientists have turned from cloning to genetic engineering as the most promising way to “eliminate extinction” or revive species that have become extinct (SN: 10/7/20). But unlike cloning, genetic engineering will not create an exact replica of an extinct species. Instead, this technology will modify the genome of an existing animal so that it resembles the genome of a desired extinct animal. The challenge is to make this agent as similar to an extinct species as possible.

To explore the limits of this method, the researchers attempted to recover the genome of the Christmas Island rat. By comparing parts of the extinct mouse’s genetic instructions book with the genome of a living relative, the Norwegian brown rat, the team was able to recover about 95% of the extinct genome. It sounds like a lot, but it means it 5% of genes are still missingincluding some important elements for smell and the immune system, scientists reported on April 11 current biology.

“You can only take back what you can find. Our view is we can’t find everything,” says Tom Gilbert, an evolutionary biologist at the University of Copenhagen.

To obtain the genome of the extinct rat, Gilbert and colleagues took ancient DNA from two rat skin samples preserved on Christmas Island. ancient DNAextracted from specimens that have died anywhere from a few decades to thousands of years, are far from perfect (SN: 5/19/08). Gilbert’s Genome of Extinct Species describes it as a book shredded. One way to rebuild this torn book is to scan the parts and compare them to a reference.

Using an intact copy of the original book, anyone could theoretically reconstruct the book perfectly. When identifying a reference genome, researchers look for species that diverged evolutionarily from recently extinct species—in other words, a very similar book. The genomes will match up closely, but not completely.

For this reason, the Christmas Island mouse (Ratus McCleary) was an obvious choice of analysis for scientists. diverged from its closest relative, the Norwegian brown rat (norwegian rat), only about 2.6 million years ago.

The team found that the genome of the Christmas Island rat has been mapped to about 95 percent of the genome of the brown rat in Norway. Additional analyzes showed that the approximately 5% missing could not be explained solely by a defect in the technique or an inappropriate reference genome. Instead, due to the evolutionary difference between the two species, most of that genetic information has simply been lost.

Moreover, the missing genes were not random. It tends to fall into two main areas that control rats’ immune responses and their sense of smell. So, if the genome of the Norwegian brown rat was modified to resemble a Christmas Island rat, the new creature would smell differently than the prototype. This could hinder the chance of the Christmas Island rats to survive if released into their former habitat.

Picture of two Norwegian brown mice in the grass
Norway brown rats (shown) and the extinct Christmas Island rats are close relatives. But the rodents still diverged evolutionarily enough to make using genetic engineering to eradicate the Christmas Island rat difficult.Dave Bevan / Alami Stock Photo

Gilbert doesn’t think anyone would likely attempt to eradicate mice. But he says what the team has shown may be useful to people working on more ambitious projects, such as bringing back woolly mammoths. The difference between the Norwegian brown rat and the extinct Christmas Island rat, for example, is similar to the divergence between the Asian elephant and the woolly mammoth.

“By doing these kinds of analyzes, which aren’t hard to do, you can at least come up with what you’re going to get, and what you won’t get, and you can use that to decide if it’s worth doing,” Gilbert says.

Despite the hurdles, using technology to bring back species is still something worth doing, says Ben Novak, chief scientist at Revive & Restore, a nonprofit that uses genetic engineering for conservation projects. He plans to apply Gilbert and colleagues’ analysis to his own work on the passenger pigeon, which became extinct in 1914. He adds that there are potential solutions for how to capture some of the missing data, but the fact that some of the data will always remain the same. The missing is one limitation that de-extinction scientists have already found.

“The problem of reference aggregation will always remain a barrier to eliminating extinction,” Novak says. “Anyone seeking de-extinction has to settle on the fact that we want to get as close as possible to something that is deceiving the environment.”

In other words, an extinct mammoth created using genetic editing, if such a thing happened, wouldn’t be quite a mammoth; It would be akin to an Asian hairy elephant that is adapted to survive in the cold. The new analysis suggests that the alternative animal version likely had enough differences that it would be difficult for the creature to repopulate its previous ecological niche. For some, this may be enough to defeat the purpose of the exercise.

“As a science, it’s cool,” Gilbert says. But “Is this the best use of money in a world where we can’t keep rhinos alive?”

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