Contact: dkenney@mbl.edu; 508-685-33525

WOODS HOLE, Mass. -- How did the monstrous giant squid – reaching school-bus size, with eyes as big as dinner plates and tentacles that can snatch prey 10 yards away -- get so scarily big?

The giant squid has long been a subject of horror lore. In this original illustration from Jules Verne’s “20,000 Leagues Under the Sea,” a giant squid grasps a helpless sailor. Credit: Alphonse de Neuville

Today, important clues about the anatomy and evolution of the mysterious giant squid (Architeuthis dux) are revealed through publication of its full genome sequence by a University of Copenhagen-led team that includes scientist Caroline Albertin of the Marine Biological Laboratory (MBL), Woods Hole.

Giant squid are rarely sighted and have never been caught and kept alive, meaning their biology (even how they reproduce) is still largely a mystery. The genome sequence can provide important insight.

“In terms of their genes, we found the giant squid look a lot like other animals. This means we can study these truly bizarre animals to learn more about ourselves,” says Albertin, who in 2015 led the team that sequenced the first genome of a cephalopod (the group that includes squid, octopus, cuttlefish, and nautilus).

Led by Rute da Fonseca at University of Copenhagen, the team discovered that the giant squid genome is big: with an estimated 2.7 billion DNA base pairs, it’s about 90 percent the size of the human genome.

Albertin analyzed several ancient, well-known gene families in the giant squid, drawing comparisons with the four other cephalopod species that have been sequenced and with the human genome.

She found that important developmental genes in almost all animals (Hox and Wnt) were present in single copies only in the giant squid genome. That means this gigantic, invertebrate creature – long a source of sea-monster lore – did NOT get so big through whole-genome duplication, a strategy that evolution took long ago to increase the size of vertebrates.

So, knowing how this squid species got so giant awaits further probing of its genome.

“A genome is a first step for answering a lot of questions about the biology of these very weird animals,” Albertin said, such as how they acquired the largest brain among the invertebrates, their sophisticated behaviors and agility, and their incredible skill at instantaneous camouflage.

“While cephalopods have many complex and elaborate features, they are thought to have evolved independently of the vertebrates. By comparing their genomes we can ask, ‘Are cephalopods and vertebrates built the same way or are they built differently?’” Albertin says.

Albertin also identified more than 100 genes in the protocadherin family -- typically not found in abundance in invertebrates --  in the giant squid genome.

“Protocadherins are thought to be important in wiring up a complicated brain correctly,” she says. “They were thought to be a vertebrate innovation, so we were really surprised when we found more than 100 of them in the octopus genome (in 2015). That seemed like a smoking gun to how you make a complicated brain. And we have found a similar expansion of protocadherins in the giant squid, as well.”

Lastly, she analyzed a gene family that (so far) is unique to cephalopods, called reflectins. “Reflectins encode a protein that is involved in making iridescence. Color is an important part of camouflage, so we are trying to understand what this gene family is doing and how it works," Albertin says.

In a rare event, a live giant squid (Architeuthis dux) is hauled to the surface on a baited hook in Japan. The giant squid can be 40 feet long tip-to-tail and weigh nearly a ton. Credit: Tsunemi Kubodera

“Having this giant squid genome is an important node in helping us understand what makes a cephalopod a cephalopod. And it also can help us understand how new and novel genes arise in evolution and development,” she says.

Citation: Rute R. da Fonseca, et al (2020) A draft genome sequence of the elusive giant squid, Architeuthis dux. GigaScience, DOI: 10.1093/gigascience/giz152

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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery – exploring fundamental biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago

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By Raleigh McElvery

A juvenile crab looks at its reflection. Credit: Virginia Garcia.

WOODS HOLE, Mass. – A longstanding goal in neuroscience is to classify the brain’s many cells into discrete categories according to their function. Such categories can help researchers understand the complex neural circuits that ultimately give rise to behavior and disease. However, there’s little consensus about what metrics should define a cell’s identity.

In a new study, a collaboration born in part from the Neural Systems & Behavior (NS&B) course at the Marine Biological Laboratory tests the notion that a cell’s identity can be described solely by the genes it expresses. The study, published in Proceedings of the National Academy of Sciences, advocates a more “multimodal” approach to defining cell identity.

By using popular and powerful RNA sequencing techniques, researchers can take a snapshot of all the genes that are currently turned on inside a cell. But it’s becoming increasingly clear that such strategies may be limited in their ability to give a complete picture of cell identity, or represent changes over time.

Along with their collaborators, NS&B instructors Hans Hofmann, David Schulz, and Eve Marder put two popular RNA-based methods to the test: single-cell RNA sequencing and quantitative RT-PCR. They applied these techniques to two well-studied nerve clusters in the crab Cancer borealis — the stomatogastric and cardiac ganglia —which allowed them to compare the results from the RNA-based approaches to other known metrics of cell identity.

The stomatogastric ganglion, which helps the crab chew and filter food, tagged with green fluorescent proteins. Credit: Adam Northcutt

They found that the cell identities generated by the complete RNA profiles, or “transcriptomes,” did not match the existing cell identities they had compiled over years of observation. In fact, categorizing cells based on their entire transcriptome ultimately yielded “scrambled” identities.

However, as the researchers further refined their selection of key genes to input into their analysis, the RNA profiles began to more closely resemble the identities gleaned from other attributes, such as innervation patterns, morphology, and physiology. Thus, this multimodal approach has the potential to reveal a more accurate portrayal of cell identity than RNA sequencing alone.

According to Hofmann, most studies don’t bother to validate transcriptomic data with other metrics of cell identity like morphology and physiology. “Classification and characterization of cell types is often performed within the context of specific studies, and not based on a systematic approach,” he says. “We really have to collect a lot of additional data, even across species, to come up with a robust taxonomy of cell types.”

“RNA sequencing is tremendously promising and powerful, but this study provides a valuable and necessary check,” Schulz adds. “Rather than relying entirely on analytics applied blindly to cell type, whenever possible it’s important to consider multiple modalities of information as well.”

The trick, Hofmann and Schulz agree, is knowing which data are indicative of cell identity, and which are simply noise that will interfere with accurate classification.

Researchers must also eventually agree on a definition of “cell identity.” Drawing firm boundaries between cell types is useful in many ways, but may ultimately be problematic.

“Soon,” Schulz says, “we'll start to see the limitations of trying to impose very discrete categories on the spectrum of cell types within and across individuals.”

Citation:

Northcutt, A.J. et al (2019) Molecular profiling of single neurons of known identity in two ganglia from the crab Cancer borealis. Proc. Natl. Acad. Sci., DOI: 10.1073/pnas.1911413116

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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery – exploring fundamental biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the MBL is a private, nonprofit institution and an affiliate of the University of Chicago.