Ants give away the secrets of human brain processes

Through their work on the brains of ants, a team of researchers at the University of Copenhagen has identified fundamental DNA networks which, with all likelihood, control brain activity. The discovery was recently published in the scientific journal Nature Ecology and Evolution. The method can be used to explore correlations between general brain functions and social behaviour.

Which genes need to be switched on and off to keep the human brain going – and which proteins are involved in the process? This is both the key question and one of the great enigmas facing brain research.

And, according to Guojie Zhang, Professor and Lundbeck Foundation Fellow at the Centre for Social Evolution at the University of Copenhagen (UCPH), studying this issue poses both technical and ethical challenges:

“You can’t just insert measuring apparatus into a human brain. So, when we researchers want to try to understand the fundamental DNA-controlled processes and networks responsible for human brain activity, we mostly have to work with other organisms. We have to find organisms which are both eligible for the studies from an ethical point of view and suitable based on a technical, biological assessment.”

Ants are highly useful for this purpose. This is proven by an article recently published in the scientific journal Nature Ecology and Evolution by Guojie Zhang, Rasmus Stenbak Larsen, Bitao Qiu and Head of the Centre for Social Evolution Professor Jacobus Boomsma.

The article was written in collaboration between the UCPH team and colleagues from research centres in China and Taiwan, and one of its main points is to show that it is actually possible, by studying ants, to identify the fundamental DNA networks that control brain activity.

This paves the way for the use of ants as model animals in trials to improve our understanding of the way in which similar functions are regulated in a human brain. And this is the research for which Guojie Zhang, who headed the studies on which the Nature Ecology and Evolution article is based, received a five-year grant when the Lundbeck Foundation made him a Fellow in 2015.

Common social features
But why choose to work with ants as model organisms if you ultimately want to try to identify DNA networks behind fundamental human brain functions?

The answer is a combination of several factors. For instance, both ants and human beings establish and live in sophisticated social structures – and this results in a number of common social features. In principle, it must be assumed that this makes the demands biology imposes on the respective brain functions more comparable.

That said, according to Professor Jacobus Boomsma, who has researched social insects since the 1970s, it is also important to emphasise that, in more general terms, we cannot make direct comparisons between the human brain and an ant’s brain:

“Of course, there are huge differences between the brain of a mammal such as a human being and that of an insect such as an ant – and the social stereotypes we see in ants, in the form of queens and workers, are extreme. But with respect to a number of fundamental brain processes, there are genes we have in common with ants – and they with us. It is these genes, and the networks to which they belong, we’re trying to understand.”

Removing the ant’s brain
A powerful microscope is essential if you want to work with the brains of ants, as they do at the Centre for Social Evolution at the University of Copenhagen, because an ant’s brain measures only 0.5 millimetres and it must be removed in one piece.

“We cut open the skull with a razor blade and then lift out the brain using tiny tweezers. There’s no room for a shaky hand,” says Lisa Brandenborg. Lisa is a Masters student in biology and is helping Guojie Zhang with this part of the research project.

By the time Lisa Brandenborg takes out her razor blade, the ant is well and truly dead – killed swiftly and observing all the rules, using liquid nitrogen at -196oC. The exposed brain of the ant, which to the naked eye looks like an insignificant dot, almost like a pin head, is then subjected to a wide range of extremely complex DNA analyses.

These analyses are conducted in China, at the Beijing Genomics Institute (BGI) in Shenzen. They register how certain networks of genes in the ant’s brain are switched on and off, and which proteins are produced.

And Professors Zhang and Boomsma explain that another reason why ants are so good as model organisms for this branch of brain research is their organisation of division of labour.

Ants make use of many different types of social model when procuring food or defending the nest, but the great majority of the world’s approximately 15,000 species of ant have a queen and a large number of workers – different castes, each with their own specific duties throughout their lives.

If we compare the queen’s personal DNA with the DNA of her sister ants from the worker caste, there will be a high level of convergence. The same will be the case if we compare the DNA of two sisters of our own species – homo sapiens, human beings. But, according to Professor Guojie Zhang, special conditions apply to the ants:

“The queen is many times larger than her sister worker, and they’re unnaturally different in general. If two human sisters were this different, one would be three metres tall, weigh 500 kilograms and be a pure zombie breeding machine; the other would only be one metre tall and weigh 14 kilograms, all of her sexual organs would be switched off and, in reality, she would merely be a socially programmed robot, taking care of household duties.”

Since, for the most part, the queen ant and her sister worker have the same DNA, the explanation for this huge divergence in their development must be connected to the way in which these genes are switched on and off – as their brains regulate growth. “And if we can begin to understand this, we’ll be able to see the contours of some of the fundamental brain networks at the heart of expression of complex behaviour patterns,” says Bitao Qiu, PhD student at the Centre for Social Evolution and first author of the scientific article.

“The on-off patterns we see in ants with regard to genes are actually the result of the effects of interaction between heredity and environment. And, since the evolutionary history of the ant is extremely long – all 15,000 species are descendants of a single ant which existed around 130 million years ago – we can say with confidence that we’re dealing with something very original. It’s fascinating.”

Five species in the laboratory
In recent years, various research teams around the world have studied DNA networks in the ant brain. However, the study led by Guojie Zhang is the first to explore these networks in several ant species simultaneously.

The advantage of this approach is that if we find the same DNA networks and on-off characteristics in several ant species, we can see that it is something fundamental – something that applies to all ant species.

“We studied five different species of ant, including the black garden ant, which is the ant most of us are familiar with. And, although there are around 15,000 ant species worldwide, we can say that we’ve found DNA networks which are seemingly at work in all ant brains. This is what we prove in the scientific article – and we do it using a range of sophisticated, statistical tools to analyse extremely large volumes of data,” Professor Guojie Zhang explains.

The researchers at the Centre for Social Evolution took 30 workers and 30 queens from each of the five species – 300 ants in all. All were killed and had their brain removed. The brains of each worker and each queen were then examined.

Professor Jacobus Boomsma explains that including even more ant species will enable them to refine this type of study over time – and, by studying certain factors in ants and other social insects, it should be possible to gain a better understanding of how DNA networks and environmental factors work together in connection with brain-related social conditions.

“These days, neuroscientists are increasingly focusing on the genetic factors underlying mental disorders, but it’s a difficult field to get into – precisely because, in addition to the genetic factors, there are many environmental effects at play. In this context, research will also be able to benefit from social insects other than ants, such as honey bees,” says Guojie Zhang, and he mentions a scientific report published by American researchers in 2017.

The report describes an experiment in which scientists deactivated – or knocked out – a gene in worker bees. This particular gene is associated with level of social function in bees, and when the gene was not active, the worker bees showed signs of social withdrawal and impaired performance. This is also a characteristic of many psychological disorders in humans.

Professor Jacobus Boomsma believes that the scientific understanding of social behaviour will be enhanced by a research field currently in rapid development:

“It concerns gut bacteria which, in many species, have proven to be able to communicate with the brain. And we can use ants as experimental model systems to investigate this further. They’ll be brilliantly suited to this, as they were in the current study.”

We can use studies of this kind to gain an understanding of which brain genes play key roles when social organisms regulate their behavioural patterns in active cooperation with both external and internal environmental effects – and to try to understand the ‘conversations’ between a brain and ‘its’ gut bacteria.

 

Ancient ant research

The Chinese wanted to keep their citrus fruit safe – so they teamed up with ants.

Chinese botanist Ji Han is the brains behind one of international ant research’s truly spectacular articles. The article can be found in Nan Fang Cao Mu Zhang (Plants and Trees in the Southern Regions), which was published by Ji Han in AD 304.

In his article about the Asian weaver ant (Oecophylla smaragdina), Ji Han describes how fruit growers in what was then the Jiao-zhi Province discovered a way to protect their citrus trees from insect pests. They placed colonies of weaver ants in the treetops and the ants then killed and sucked the nourishment from the various pests which had colonised the trees.

Later sources reveal that the Chinese fruit growers eventually refined their method of insect control by laying long bamboo canes between the tops of the fruit trees. This created a kind of walkway, enabling the weaver ants to travel freely throughout the plantation and establish new nests in all of the trees.

But are weaver ants effective when it comes to killing insect pests?

Current studies indicate that they are highly effective – and, once they have done their job, the Asian weaver ants can be ‘harvested’ and provide human beings with a valuable source of protein. Weaver ants, which are considered a delicacy in Thai cuisine, actually contain as much protein as pork.

When Ji Han wrote about Oecophylla smaragdina in AD 304, he also noted that fruit growers in Chinese provinces which had not adopted this method of insect control regularly faced “insect pest attacks so massive that not a single piece of fruit could be harvested in perfect condition”.

Facts: Colonies of ants
Ants live in complex societies – in colonies. The individual ants communicate with the help of chemical substances which are used to create a colony odour.

The colony odour is due to hydrocarbon molecules located on the exterior of the insect, and each colony has its own specific odour. If an ant strays into another colony, which has different colony odour, it will smell wrong – and will be killed.

This colony odour can be compared with a bar code. Within one ant species there will be a number of similarities between the bar codes of the individual colonies, but each colony will have its own specific code. And the differences between the bar codes of different species of ant will be much more pronounced.

For further details please contact:

Jacobus Boomsma, tel. +45 3532 1340

Guojie Zhang, tel. +45 9185 5431

Henrik Larsen, science journalist at the Lundbeck Foundation, tel. +45 2118 6377 or hl@lundbeckfonden.com

 

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