Building bigger brains

Bottlenose dolphins have an average brain mass of 1.6 kg, slightly greater than that of humans, and about four times the size of chimpanzee brains.

Although you couldn’t really imagine a dolphin writing poetry, dolphins demonstrate high levels of intelligence and social behaviour. For example, they display mirror self-recognition, as well as an understanding of symbol-based communication systems.

Research into the differing brain sizes and intellectual capabilities within the animal kingdom is fascinating.

Why have some species evolved to be more intelligent than others? Does brain size affect cognitive ability?

Some studies say yes, but some insist otherwise. It really depends which species we are talking about.

In humans, for example, larger brains do not indicate higher intelligence – otherwise Einstein, who had an average-sized brain, may have not been quite as successful in his career. (Yes, that link was to a 23-pager on the analysis of Einstein’s brain. It makes for great bedtime reading.) Most neuroscientists now believe that it is the structure of the brain on a cellular and molecular level that determines its computational capacity.

Within certain animal species however, a larger brain offers evolutionary advantage. For example, large-brained female guppies are better survivors and demonstrate greater cognitive strengths than their smaller-brained counterparts.

Although the relationship between brain size and cognitive abilities of vertebrates has been widely studied, the mechanisms underlying how many species have evolved larger brains have proven difficult to decipher.

A group of evolutionary biologists from UCL, Stockholm University and the

University of Helsinki set out to explore this unknown, aiming to determine the genetic architecture underlying the evolution of brain size variation in guppies and zebrafish.

Animal modelling careers: Zebrafish and guppies make the cut

Why did the researchers choose zebrafish and guppies? Well, these fish species make good model organisms for neural development because their genetic makeup as well as the genetic pathways controlling their development are highly similar to those of humans. And although the brain structure of the zebrafish does differ to the human brain in certain regions, their overall organisation is also similar. Guppies, a species of freshwater aquarium fish, are often used in research because of their short life span and therefore short generation time, in addition to their ease of breeding and high reproductive capacity.

The researchers carried out their experiment to mimic evolutionary change in fish over a short period of time. First, they selectively bred guppies to have either small or large brains, creating a 9% difference in brain size between two groups of fish. This variation saw significant distinctions in cognitive abilities between the two fish populations.

Then, to identify the genes underlying these differences in brain size, the researchers did a full genome expression analysis of the large- and small-brained guppies. They found one gene that stood out: Angiopoietin-1 (Ang-1) expression was much greater in the larger brained guppies.

Ang-1 is not a gene that is typically studied for its contribution towards determining brain size. However, the protein encoded by Ang-1 is known for its importance in the development of blood vessels (angiogenesis) in humans.

Ang-1 has also recently been found to play a role in the growth and development of neurons – making it a potential key player in the shaping of brain size and cognitive evolution in vertebrates.

To explore the significance of Ang-1 in brain size variation, the researchers next did ‘knock-out’ experiments in zebrafish embryos. They deleted the expression of Ang-1 in zebrafish and then looked for any effects on brain size. Interestingly, the knock-out caused morphant zebrafish to have significantly smaller brains than those of the controls.

 Brain morphology of a zebrafish Ang-1 morphant. <br><br>Knockdown of Ang-1 expression caused a small brain in the Ang-1 <br> morphant (right) compared with the control brain (left). <br><br>Dashed lines illustrate the brain area.
 Brain morphology of a zebrafish Ang-1 morphant. Knockdown of Ang-1 expression caused a small brain in the Ang-1 morphant (right) compared with the control brain (left). Dashed lines illustrate the brain area.

That a single gene can have such an effect on brain growth suggests that the genetic architecture affecting brain size may be much simpler than anticipated. One of the authors, Judith Mank from UCL Biosciences, said, “We were surprised to see that only a single gene was up-regulated in the large-brained guppies. Given the complexity of the brain, we expected that the genetics would be very intricate, but this suggests that changes in brain size are underpinned by relatively simple genetic mechanisms.”

Directly and indirectly growing brains

Mank and her co-workers propose that Ang-1 is a key gene underlying evolutionary changes in vertebrate brain size and cognitive abilities. However, there are still many questions to answer. For example, does modifying Ang-1 expression directly alter brain size via neural growth, or indirectly – through stimulating angiogenesis?

Larger brained guppies may have a higher expression of Ang-1 because they need more blood vessels to ensure an adequate blood supply for these big brains. This may also be why zebrafish Ang-1 morphants grew smaller brains – the fish could not grow enough blood vessels to sustain such a large brain. Future studies focusing on the pathways that Ang-1 stimulates will be needed to gain a better understanding into this brain growth gene’s mechanism of action.

This study represents quite a swim in the direction towards outlining the growth patterns characterising fish brain-volution (as I like to call it). The authors are now interested in how modifying Ang-1 levels affects other aspects of a fish’s lifetime.

Future experiments investigating Ang-1 in different species will help determine whether this role of Ang-1 extends to other species, including its relevance to human brain development.


This article was originally posted on the Guardian Online.

Chen YC, et al. 2015 Expression change in Angiopoietin-1 underlies change in relative brain size in fish.
Proc. R. Soc. B 282:20150872.



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