It’s a Lefty! Welcome to the World’s First Crispr Snail Baby

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Science|It’s a Lefty! Welcome to the World’s First Crispr Snail Baby

Trilobites

Most snails are righties. Now scientists have found genes that make some of them born with shells coiling the other way.

ImageIt’s a Lefty! Welcome to the World’s First Crispr Snail Baby
A garden snail, the same type of snail as Jeremy, the left-coiled snail who made headlines in recent years as he searched for a same-spiraled mate.CreditCreditBecky Jones/University of Nottingham

The overwhelming majority of snails live in shells that coil to the right. But occasionally some are born with shells that turn the other way.

And then there was Jeremy, the garden snail with a left-coiled shell. His struggle to find a left-coiled mate made him famous. Just before dying in 2017, he was finally paired up, leaving behind a litter that was born all right.

How Jeremy and other chiral or mirror-image snails — including a few species that are all-left — turn out like this has long baffled scientists. Studying these snails offers clues to the evolution of body plans in many animals. It also could be important for understanding why approximately 1 in 10,000 people are born with situs inversus, a condition where their internal organs are flipped like a lefty snail’s shell.

Now scientists are turning to Crispr — the powerful gene editing tool — to figure out why some snails turn out this way. A team in Japan led by Reiko Kuroda, a chemist and biologist, has successfully used the technique to manipulate a single gene responsible for shell direction in a species of great pond snail. The research, published last week in the journal Development, offers definitive proof of the genetic underpinnings of handedness in this species, and could lead to clues about left- and right-handed mysteries in other organisms.

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“Ten years ago you might not imagine there were any similarities in the left/right asymmetry of a snail and the left/right asymmetry of humans. But it’s becoming increasingly obvious that is the case,” said Angus Davison, an evolutionary geneticist who has studied Jeremy the lefty snail as well as chiral pond snails, but was not a part of Dr. Kuroda’s study.

Video
Dividing of embryonic snail cells that underwent gene editing. Video by Masanori Abe and Reiko KurodaCredit

A few years ago, Dr. Kuroda and Dr. Davison’s groups independently stumbled upon Lsdia1, a gene that might explain shell direction. But lefties had one less copy of the gene than righties, and compensated with a nearly identical gene, Lsdia2. Which one caused the handedness?

In the current study, Dr. Kuroda and Masanori Abe used Crispr to edit out the Lsdia1 gene, and then raised the resulting mutant snails. Confirming previous work, they showed that even in the first embryonic cell, genetic information started picking sides. And by the third cleavage, when four cells become eight, the mutant cells were rotating in the opposite direction of what is expected.

These snails grew into lefties, and so did their offspring. Without two working copies of Lsdia1, snails can survive with Lsdia2 — but their shells won’t coil to the right.

Dr. Kuroda still wants to know how the genes work together and whether lefty pond snails could one day become their own species like the few all-left snail species that exist now.

Dr. Davison says this is unlikely: Only about half of lefty pond snails ever hatch. And though most can’t, a few lefty snails can manage to mate with righties.

Still, the genetics behind pond snails becoming lefties or righties conjures questions about why it developed and evolved in so many organisms.

“Chirality is pretty universal. Most organisms have left/right asymmetry,” said Nipam Patel, a cell biologist who found that humans, other vertebrates and snails share some similar roads on the genetic map to mirror-image bodies. These organisms initially break symmetry in different ways, but eventually they likely merge onto the same path, taken by a common ancestor long ago.

“There is likely no universal molecule gene that switches asymmetry,” Dr. Davison said. “But it is possible that there is a universal pathway that is involved in setting up an asymmetric cellular architecture in all animals.”

As for Jeremy, Dr. Davison will be studying the lefty garden snail’s great-grand-snails for clues to what made their progenitor’s unusual coil.

“We’ve got a lab full of snails, lots and lots of them, but we’re still working to try and understand what it was that made Jeremy a lefty,” said Dr. Davison. “Unfortunately, snail research doesn’t move quickly.”

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Correction: 

An earlier version of this article misstated the number of people who have the condition known as situs inversus. It is approximately 1 in 10,000 people, not up to 10 percent.