Bigger brains may allow greater cognitive ability, but they also come with a significant cost: they are extremely energy hungry organs, and it takes a lot to build and maintain a big one. Attempting to strike a balance between these pros and cons is why researchers believe such incredible variation in brain size exists among vertebrates. And while these size differences are well documented, little is known about the underlying genetic mechanisms.
But it seems scientists are slowly beginning to piece together this puzzle. A few months ago, scientists found that a human gene, when inserted into mice, boosted their brain size to a greater extent than the same stretch of DNA from chimps. Now, researchers have discovered that a single gene may underpin both brain size and cognitive ability in fish.
In two different fish species, those who were smarter and had bigger brains were found to boast ramped up expression of this gene, called Angiopoietin-1 (Ang-1). And when the researchers quietened it down experimentally, a decrease in brain size was also observed. Because the same patterns were found in two distinct species, the researchers think that the same genetic architecture is probably at play in others.
“Other genes may be involved in brain growth in young, developing fish but no other genes were found to vary in their expression in adult fish other than Ang-1,” study author Niclas Kolm from Stockholm University said in a statement. “Future studies will aim to investigate the role of Ang-1 and possibly other genes in the formation of differently sized brains in developing embryos.”
For the study, published in Proceedings of the Royal Society B, the researchers began by artificially selecting for big or small brained guppies with associated variations in cognitive ability. Those at the lower end of the spectrum had brains 10% smaller than those at the other end. After examining patterns of gene expression, the researchers found that only one displayed significant differences between these populations: Ang-1.
“We were surprised to see that only a single gene was up-regulated in the large-brained guppies,” study author Judith Mank from University College London said in a statement. “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.”
To further explore this apparent link, the researchers modified the genomes of zebra fish so that expression of Ang-1 was decreased, but not abolished. Supporting the previous findings, these fish developed significantly smaller brains than control fish.
Angiogenesis is the process of forming new blood vessels in the body, so as you’ve probably gathered, Ang-1 is critical to this, not just in fish but in humans also. Because bigger brains will require more vasculature than smaller ones to ensure a sufficient supply of blood, it’s possible that the observed expression differences in Ang-1 indirectly influence brain size by changing angiogenesis. However, it’s been demonstrated in mice that Ang-1 contributes to the formation of new brain cells, which could indicate that it also plays a direct role in determining brain size.
It’s unclear at this stage whether similar mechanisms are at play in humans, and Ang-1 had not previously been considered as a candidate involved in determining human brain size. But the researchers hope to delve into this further by examining its expression in other vertebrates.