There is a correlation between the brain size of an individual and their body size: a larger animal needs a larger a brain to take care of their basic bodily functions. However, some creatures deviate from this relationship and have a significantly bigger brain than would be expected given their body size. This is known as encephalisation.
Humans are highly encephalised with a brain volume of 1,350 cc. This is nearly three times the size of a chimp (450 cc) despite the fact we have nearly the same body mass as them. Given that our brain is energetically expensive and takes a long time to grow, increasing the length of infancy, it must have given our ancestors some pretty big benefits to make it worthwhile.
And we do indeed gain some great advantages from having a larger brain. In the beginning it would’ve allowed us to live in larger groups and adapt our behaviour to suit a variable environment. As it increased in size it would also allow us to make better tools and eventually engage in modern, complex behaviour.
Although we have a fairly good understanding of why our brains got bigger the “how” is still a bit of a mystery. What mutations were responsible for the change? How did these mutations alter protein production? Why does my big brain not stop exams being scary?
New research seems to have found an answer to at least a few of these questions (alas, it won’t help my revision), claiming to have identified the evolutionary history of SRGAP2, a gene responsible for the protein SsrGAP2.
Genes make proteins by making amino acids (the building blocks of proteins) line up in the right order, a process known as translation. SsrGAP2 is made by two copies of SRGAP2′s amino acids joining together. The resulting protein has two pretty key functions in brain development.
Firstly it controls how long the spine grows. Now, this isn’t the spine as in “the spine which runs down our back.” No, this controls the development of spines of neurons (i.e. dendrites). Secondly, it controls how fast neurons move from where they first form to where they are meant to go. It does this by making them grow branches in front of them, slowing down the rate they migrate.
The scientists studying SRGAP2 – the gene responsible for the amino acid incest – found that humans have four copies of this gene unlike other animals. We are lucky enough to have SRGAP2A, B, C and D whilst our ape relatives have just the one version. Further, SRGAP2 A-D aren’t identical. These genes have mutated since they appeared.
Since the gene is identical in chimps and orang-utans (both in terms of number of genes and the structure of that gene) the differences between apes and humans would have had to have arise on the human lineage, after we had diverged from chimps. This means some kind of duplication event(s) occurred between 5-7 million years ago and today.
So the researchers looked at the human genes to try and figure out which gene duplicated into which copy. Interestingly, they found duplicates B-D were incomplete. This means that SRGAP2A was the common ancestor, which was then partially duplicated at some point. You can’t have it the other way, with B-D duplicating stuff that didn’t exist in them!
But did each of B-D come from A? Or did A duplicate into B, which duplicated into C etc? To answer this, the researchers compared how similar these duplicates were to each other, with more similar genes being more related. They found that A duplicated in B, which in turn duplicated into both C and D.
As you can see from the above diagram, the scientists also tried to calculate when these duplication events occurred. Obviously the genes absence in apes indicates it was some time between 7 million years ago and now, but that is rather vague. So they looked at the number of genetic differences between each of the duplicates and worked out how long they would’ve taken to accrue.
The interesting thing about gene duplication is that new copies of the gene have less pressure to remain the same. The original gene is already there, working away, so the new copy can change as it wants and natural selection won’t stop it. Mutations won’t really be harmful since the original copy can act as a “backup” if something breaks the duplicate.
As such duplicates typically mutate at a faster rate, which could throw off their calculations somewhat. However, the researchers were able to identify how much faster these duplicates mutated. They did so by looking at a non-functional piece of DNA that had been duplicated along with the SRGAP2 genes and seeing how much it had changed.
Since natural selection wouldn’t remove any mutations these parts of the DNA act as a good molecular clock, recording all the mutations that have happened to it. As such the researcher could get an understanding of how many mutations have happened and sotake this into account, making their calculations more reliable.
The results they came up with were 3.4 million years ago for the first duplication, from SRGAP2A to B. Then 2.4 million years ago B duplicated into C and only 1 million years ago B also became D.
These dates means that both neanderthals and Denisovans should have had these mutations since they diverged after the duplications allegedly arose. So the scientists looked to see if they did and lo’ they were right, both groups had these duplicates. This lends further credibility to the age calculations.
So we know what mutated and we know when it mutated. But what was the result of this mutation? Well, as I mentioned the main function of this gene is to control the development of spines on neurons and how fast these neurons move around.
These mutations are incomplete meaning that if the product of SRGAP2A combined with SRGAP2B/C to form a protein (remember, this protein is formed by two copies of the amino acids produced by the gene fusing together) then that protein would have lost some functionality. This loss of functionality appears to stop the SsrGAP2 protein working properly.
This loss of function means it can’t regulate spine growth properly. As a result they grow for longer, resulting in much denser spines. Preliminary research suggests that thicker spines can receive information from more neurons. This would enable more neurons to connect to each other, enhancing brain connectivity and intelligence. However, this conclusion should be taken with a grain of salt since the results are, as I just said (pay attention), preliminary.
More rigorous tests have revealed that by loosing functionality SsrGAP2 makes neurons create fewer branches ahead of them. Since these branches slow the neurons down as they move around the brain, this mutation would result in faster migration. This would speed up the development of the brain.
As such, whilst this mutation would not have directly resulted in encephalisation it would’ve removed one of the hurdles in its way. This might explain why these mutations occurred around the same time humans started to become very encephalised.
|Charrier, Cécile, Kaumudi Joshi, Jaeda Coutinho-Budd, Ji-Eun Kim, Nelle Lambert, Jacqueline de Marchena, Wei-Lin Jin, et al. 2012. ‘Inhibition of SRGAP2 Function by Its Human-Specific Paralogs Induces Neoteny During Spine Maturation’. Cell 149(4):923–935|
|Dennis MY, Nuttle X, Sudmant PH, Antonacci F, Graves TA, Nefedov M, Rosenfeld JA, Sajjadian S, Malig M, Kotkiewicz H, Curry CJ, Shafer S, Shaffer LG, de Jong PJ, Wilson RK, & Eichler EE (2012). Evolution of Human-Specific Neural SRGAP2 Genes by Incomplete Segmental Duplication. Cell, 149 (4), 912-22 PMID: 22559943|
|Guerrier, Sabrice, Jaeda Coutinho-Budd, Takayuki Sassa, Aurélie Gresset, Nicole Vincent Jordan, Keng Chen, Wei-Lin Jin, Adam Frost, and Franck Polleux. 2009. ‘The F-BAR Domain of srGAP2 Induces Membrane Protrusions Required for Neuronal Migration and Morphogenesis’. Cell 138(5):990–1004.|
In retrospect the title of this post is kind of a “no duh.” Of course mutations helped the brain evolve, mutations are one of the driving forces of evolution!