New research suggests that microRNAs play a crucial role in the advanced development of the brain, including in humans.
Octopuses have fascinated scientists and the public with their remarkable intelligence, from using tools to engaging in creative play, problem-solving, and even escaping from aquariums. Now, their cognitive abilities may provide significant insight into understanding the evolution of complex life and cognition, including the human brain.
An international team of researchers from Dartmouth College and the Max Delbrück Center (MDC) in Germany has published a study in the journal Science Advances, revealing that octopuses are the first known invertebrates to contain a high number of gene-regulating microRNAs. The genes of two octopus species were found to have an increase in microRNAs, which are associated with the development of advanced cells with specific functions, over evolutionary time, a finding that has previously only been observed in humans, mammals, and other vertebrates.
When combined with the known intelligence of octopuses, the findings provide crucial support for the theory that microRNAs are key to the evolution of intelligent life, said co-corresponding author Kevin Peterson, a Dartmouth professor of biological sciences. The nervous systems of octopuses and squids — which both belong to a type of mollusk known as cephalopods — evolved independently of vertebrates. Yet, the prevalence of microRNAs in both octopuses and vertebrates suggests a common role for the molecules in advanced cognition.
“MicroRNAs are known as the ‘dark matter’ of the animal genome — they don’t make protein, but they regulate the expression of proteins,” Peterson said, referring to the hypothetical form of matter thought to constitute most of the universe.
“This is the only instance in all of the invertebrates of dramatic microRNA increase and those genes are all expressed in the brain,” he said. “This was always a big test for the hypothesis, that it is not specific to vertebrates. This was a big moment — we discovered the secret to complex life, and the secret to complex life is microRNAs.”
MicroRNAs were first reported in 1993 by Victor Ambros, a professor at Dartmouth from 1992-2007 who is now a professor at the University of Massachusetts Medical School. For nearly 15 years, Peterson and his research group have sequenced the genes of various animal species in order to link microRNAs to complex tissue development and brain evolution.
For the latest paper, Peterson’s group worked with the lab of co-corresponding author Nikolaus Rajewsky, professor of systems biology at MDC, which had a wealth of RNA data on octopus species, particularly the common octopus (Octopus vulgaris). Peterson and co-author Peter Chabot, of Dartmouth’s Class of 2022, worked through raw data of microRNAs sequenced from octopus species and identified specific sequences that were either new or already found in these animals. Their work provided an organized and annotated data set that was essential to the paper’s findings, Chabot said.
Peterson’s research has shown that creatures such as placental mammals whose genes have increased in number and complexity over evolutionary time also exhibit increasing concentrations of microRNAs. On the other hand, organisms such as parasites have lost ancestral genes — and microRNAs — as they have become less complex.
“In order to have new cognitive abilities and behaviors requires new cell types,” Peterson said. “The two places you get this — in placental mammals and cephalopods — is also where we see these microRNA-expressed genes. Animals that don’t seem to have changed very much in the past 500 million years don’t have very many microRNAs.
“Every time we’ve tested this hypothesis, we’ve found it very viable, and we’ve not been able to refute it yet. That’s what made this paper particularly exciting,” he said.
Octopuses possess an uncommon intelligence. In 2016, an octopus named Inky made international headlines after escaping from the National Aquarium of New Zealand by slipping through a gap in his tank and pulling himself several feet across the floor to a nearly 150-foot drainpipe leading to the sea — and his freedom. Octopuses also have been observed collecting and building shelters from discarded coconut shells and using water currents to play catch with various objects.
This kind of intelligence potentially stems from microRNAs’ role in diversifying cell function, said study co-author Bastian Fromm, a research group leader at the University of Tromsø in Norway who collaborates with the Peterson lab on its research and building the online microRNA database, MirGeneDB.
Cells in complex organisms perform specialized tasks, which means surrounding cells need to be calibrated to carry out additional functions, Fromm said.
“MicroRNAs are like light switches or dimmers that can turn on and regulate the expression of thousands of proteins in a cell and specify what the cell can do,” Fromm said. “This is a numbers game. Oysters and slugs have microRNAs, but in cephalopods — and especially the octopus — there is an explosion of them that correlates with their intelligence.”
Reference: “MicroRNAs are deeply linked to the emergence of the complex octopus brain” by Grygoriy Zolotarov, Bastian Fromm, Ivano Legnini, Salah Ayoub, Gianluca Polese, Valeria Maselli, Peter J. Chabot, Jakob Vinther, Ruth Styfhals, Eve Seuntjens, Anna Di Cosmo, Kevin J. Peterson and Nikolaus Rajewsky, 25 November 2022, Science Advances.
The study was funded by the DFG, German Research Foundation; the National Science Foundation; NASA’s Ames Research Center; Dartmouth College; the Carlsberg Foundation; the Tromsø Research Foundation the Swedish Research Council’s Strategic Research Area through Stockholm University; and the Italian Ministry of Education, Universities and Research.