Squid Rewrite Their Own Proteins on the Fly, and the Scale Is Staggering

Squid can reshape the proteins their cells build by editing genetic instructions after they are copied from DNA, and they appear to do it on a scale no other animal matches, according to a study published in the journal Cell. ScienceAlert reported that the work, led by bioscientists at the University of California, San Francisco (UCSF), maps what those edits actually do inside the longfin inshore squid.

The finding adds to a picture of cephalopods, the group that includes squid, octopus and cuttlefish, as animals with an unusually flexible biology.

What is RNA editing, and why is it unusual in squid?

Cells copy genes into RNA, which then serves as the instructions for building proteins. Humans and other animals can tweak that RNA through a process known as ADAR-mediated RNA editing, a reversible change that leaves the underlying DNA untouched. ScienceAlert compared it to changing raisins to chocolate chips in a recipe just before it reaches the baker.

Coleoid cephalopods, the group that includes squid, octopus and cuttlefish, may do this better than any other creatures, the outlet reported.

What did the researchers examine?

The team studied the proteome, the full set of proteins, of the longfin inshore squid, Doryteuthis pealeii, which the report put at approximately 24,000 proteins. They looked at nearly 8,000 sites where proteins were edited, spread across more than 2,000 different proteins, in two tissues: the optic lobe and the gills.

The optic lobe handles vision and the response to it, and it makes up a sizable part of the squid's central nervous system. It showed frequent and more complex editing than the gills, which ScienceAlert described as a more routine respiratory organ. The researchers suggest the most robust ADAR editing ability and the most complex nervous systems seen in invertebrates emerged together in cephalopods.

The edits fall in protein-coding sequences, not in the non-coding parts of the genome sometimes called junk DNA. Some of them alter the ADAR proteins themselves, which may offer a form of self-regulation.

What do the edits change?

First author Jack Moen, a cellular and molecular scientist at UCSF, told ScienceAlert that the team found effects on protein activity, stability, location in the cell and the way proteins interact with one another. He said the downstream effects reach as far as the health of organelles, the small working structures inside cells.

Edited proteins also shifted position, moving from the outskirts of cells toward the nucleus. The researchers found that recoding may make squid mitochondria, the cell's energy-producing structures, more similar to human mitochondria: more stable in changing environments and better able to recycle themselves. Recoding also appeared to affect the squid's creatine systems, which may supply bursts of energy for evasive movements or demanding brain activity.

The team also identified 5,000 short proteins that were missing from both the reference squid proteome and the Swiss-Prot database, a gold-standard collection covering 14,000 organisms. Moen said the potential to create new protein sequences was among the results that struck the team most.

How big is the potential variety?

Because each edit happens one base at a time, the number of possible combinations grows enormously. Moen told ScienceAlert that counting every site found in the RNA sequencing data brings the theoretical estimate closer to 10²⁴⁸ protein variants. ScienceAlert noted that figure far exceeds the number of atoms in the universe.

Moen cautioned that the number describes potential diversity, and how much of it the animals actually produce is unknown.

Why does it matter?

The work shows one way an animal can change its proteins without changing its DNA. Moen said this lets squid generate proteins with different properties while avoiding permanent changes to the genome that could pass on harmful mutations to offspring.

For readers, the result is a basic-science finding about how life can work, not a treatment or a product. It offers no direct health benefit for people. But it helps explain how cephalopods, which have some of the most sophisticated nervous systems among invertebrates, may adjust their cells to conditions such as temperature changes. Earlier research had linked these edits to communication in the central nervous system, the researchers say in the paper.

What is still unknown?

Why this editing is so widespread in cephalopods and not in other animals is not settled. Moen said the structure of the ADAR enzymes plays a part, along with other reasons that need more research. The study also looked at only two tissues in one squid species, so how far the findings extend to other cephalopods remains to be tested.

Around Prague, based on reporting by ScienceAlert