Squids are highly intelligent animals with complex nervous systems. But why the brains of these cephalopods have reached this level of development, which is unusual for invertebrates, has only been partially explained so far. Researchers may now have discovered an important factor in this. According to this, an unusually large number of microRNAs are active in the nervous tissue of the squid - small RNA snippets that can regulate the production of proteins. The repertoire of these microRNAs in cephalopods is the third largest in the animal kingdom and the largest in an invertebrate, the scientists found. That could explain the intelligence of these animals.
Squid are unique - no other invertebrate has developed such a complex nervous system and such high intelligence. These cephalopods have a central brain, but also a peripheral nervous system that can act partially independently: if they lose a tentacle, it remains sensitive to touch and can still wriggle. Octopus, squid and co are also enormously capable of learning, curious and have strong memories. They can even count and use tools to open shells, for example. "They say if you want to meet an alien, go diving and make friends with an octopus," says senior author Nikolaus Rajewsky of the Max Delbrück Center for Molecular Medicine in Berlin. Studies show that the large, complex brains of cephalopods rival the number of neurons and connections between brain cells in the brains of dogs and other vertebrates.
Look at the squid's RNA
But why the brains of squid are so much more developed than those of other invertebrates has only been partially explained. In search of an answer, Rajewsky, his colleague Grygoriy Zolotarov and their team studied RNA activity in 18 different tissues of the common octopus (Octopus vulgaris) and the California two-spotted octopus (Octopus bimaculoides). It turned out that the messenger RNA, which is responsible for transporting the genetic building instructions to the protein factories of the cell, is not particularly abnormal in the octopuses. However, a special feature was found in another type of RNA: In the tissues of the octopuses - and especially in the nerve tissue and brain - an unusually large number of microRNAs are active, as the researchers found.
These small pieces of ribonucleic acid do not contain any protein-coding genes. However, they can dock onto the messenger RNA and thus regulate the extent to which its code is converted into proteins. According to Zolotarov and his colleagues, 90 previously unknown families of such microRNAs were active in the two octopus species. To find out which of these are typical of all cephalopods and which are unique to advanced squid, the scientists compared the microRNA repertoires of the two octopuses, the pygmy squid Euprymna scolopes and the primitive cephalopod Nautilus. It turned out: "Of the 90 new microRNA families, twelve were found in the nautilus and the dwarf squid - they therefore represent the basic equipment of the cephalopods," the researchers report. In contrast, 43 microRNA families were only found in the octopus and the dwarf squid, and another 35 only in the octopus.
Explosive expansion of the miRNA repertoire
Accordingly, the number of microRNAs increased drastically in the course of the evolution from simple cephalopods like Nautilus to the intelligent, large-brained squid. "This is the third largest expansion of microRNA families in the animal kingdom and the largest beyond vertebrates," says Zolotarov. No other invertebrate has such a large number of microRNAs. With a total of 138 microRNA families, squid have even more than, for example, chickens, which are vertebrates. Next, Zolotarov and his colleagues investigated where and to what extent the octopus microRNAs are active. "Of the 43 microRNAs unique to the octopus, 34 were active in one or more neuronal tissues," they report. "On average, they were expressed 13 times more strongly in these tissues than in non-neuronal tissues."
The team concludes that this expansion in the repertoire of regulatory RNA fragments was crucial for the development of complex brains and nervous systems in both invertebrates and vertebrates. "The remarkable explosion of microRNA repertoires in squid could indicate that microRNAs and their specialized neuronal functions are closely linked to the development of complex brains in animals - they are probably even necessary for it," the researchers state. How exactly the small pieces of RNA drive brain development in detail must now be clarified by further studies.
Source: Grygoriy Zolotarov (Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin) et al., Science Advances, doi: 10.1126/sciadv.add9938