CRISPR's limits for resurrecting species are demonstrated by an extinct rat.

A study reveals that even a few missing genes in animals' re-created genomes could be an issue. 

In the early 1900s, the Christmas Island rat (shown) became extinct. According to a study, editing the DNA of a surviving relative of the rat could result in a creature that looks like an extinct rodent but lacks several key genes.
In the early 1900s, the Christmas Island rat (shown) became extinct. According to a study, editing the DNA of a surviving relative of the rat could result in a creature that looks like an extinct rodent but lacks several key genes.

Prior to the early 1900s, if it walked and talked like a Christmas Island rat, it was undoubtedly a Christmas Island rat. If one of these now-extinct rats ever resurfaces, it will most likely be a genetically engineered Norway brown rat. And, according to popular belief, the rodent will not be as identical to the Christmas Island rat as some would like.

Scientists have turned from cloning to genetic engineering as the most promising option for "de-extinction," or the revival of extinct species, with the development of gene-editing technology such as CRISPR (SN: 10/7/20). Genetic engineering, unlike cloning, would not produce an exact clone of an extinct species. Instead, the approach would modify the genome of a living animal to resemble that of the targeted extinct animal. The task is to make that proxy as close to the extinct species as possible.

To test the method's boundaries, researchers attempted to recover the genome of the Christmas Island rat. The researchers were able to retrieve around 95 percent of the extinct rat's genome by comparing bits of the ancient rat's genetic instruction book with the genome of a surviving relative, the Norway brown rat. That may sound like a lot, but it implies that 5% of the genome was still missing, including certain sections important for scent and the immune system, according to a study published in Current Biology on April 11.

"You can only bring what you find back." "Our point is that we can't find everything," explains Tom Gilbert, an evolutionary biologist at the University of Copenhagen.

Gilbert and his colleagues extracted ancient DNA from two preserved skin samples of the Christmas Island rat to obtain the genome of the extinct rat. Ancient DNA is far from perfect, having been taken from specimens that died anywhere from a few decades to thousands of years ago (SN: 5/19/08). Gilbert compares an extinct species' genome to a shredded book. One method for reassembling this torn book is to scan the shards and compare them to a reference.

Someone could possibly rebuild the book perfectly if they had an intact copy of the original. When searching for a reference genome, scientists aim for a species that diverged from the extinct species relatively recently — in other words, a very comparable book. The genomes will be similar but not identical.

As a result, the Christmas Island rat (Rattus clear) was an easy candidate for the scientists to study. Only about 2.6 million years ago did it divide from a close relative, the Norway brown rat (Rattus norvegicus).

The Christmas Island rat genome aligned to almost 95% of the Norway brown rat genome, according to the researchers. Further analysis revealed that the missing 5% could not be explained only by a defect in the technology or an inadequate reference genome. Rather, most of the genetic material was simply lost due to evolutionary divergence between the two species.

Furthermore, the missing information was not haphazard. Genes that were partially or fully absent tended to be found in two major areas that governed the rat's immunological responses and sense of smell. So, if the genome of a Norway brown rat was modified to resemble the Christmas Island rat, the resulting critter would smell differently than its prototype. This could reduce a proxy Christmas Island rat's chances of survival if released back into its natural home.

Gilbert does not believe that anyone will attempt to exterminate a rat. However, he believes that what the team has proven could be valuable for individuals working on even more ambitious undertakings, such as resurrecting the woolly mammoth. For example, the divergence between the Norway brown rat and the extinct Christmas Island rat is comparable to that between the Asian elephant and the woolly mammoth.

"The reference assembly problem will always be a barrier to extinction," adds Novak. "Anyone attempting de-extinction must accept that we want to get as near to something that tricks the environment as possible."

In other words, a de-extinct mammoth made through gene editing, if such a thing ever exists, will look more like a hairy Asian elephant suited to thrive in the cold. According to the new research, the proxy animal form will most likely have enough differences to make it difficult for the species to fill its previous ecological niche. For others, this may be sufficient to defeat the exercise's objective.

"It's amazing as a science," Gilbert says. However, "is this the wisest use of money in a world where we can't even keep our rhinos alive?"


J. Lin et al. Probing the genomic limits of de-extinction in the Christmas Island Rat. Current Biology. Vol. 32, April 11, 2022, p. 1. DOI: 10.1016/j.cub.2022.02.027.


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