Mutation helped human brain evolve

ResearchBlogging.orgThere 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.

Brain growth graph

Anything above the line is encephalised. Humans, as you can see, are epic

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.

SRGAP2 locations

Chromosome 1 with the location of SRGAP2 copies highlighted in red (SRGAPD is excluded because it has no real function)

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.

SRGAP2 evolution

The evolution of SRGAP2, with the products of each of the genes shown above. Not how not all of SRFAP2A is duplicated.

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.

Science says “yeah” to these results

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!

About these ads

23 responses on “Mutation helped human brain evolve

  1. This is an awesome post man! Super informative and full of stuff I had no idea it was even possible to know.


    I infer from this that we have the genetic code for neanderthals. Is that right? How?

    Perhaps you could point me in the direction of an answer to that old Creationist chestnut, “There is no known mechanism by which information can be added to a gene.” Where’s a good response to that?


      If Adam knows…he knows something Dawkins does not.

      • Outside of theoretical biology (and common, non-scientific discussion) the notion of information rarely comes up because it has many definitions, making it too vague to be useful. Some define information as the number of unique sequences, others by sheer quantity of data represented etc. Instead most genetecists and biologists talk about “function” which is much more strictly defined. Does this gene do something new? Does it do something old better/worse? etc.

        The article I was discussing, for example, only uses the word information twice. Once in reference to patient information (when discussing medical case studies) and the other in the heading supplementary information (where the equipment used was discussed).

        Changes to functionality, such as improvements to existing function or something brand spanking new, can be produced via mutations. These could occur in the gene itself, or in the gene which controls other genes, or even in genes which control the development of an organism. The field of evolutuionary development (whose nickname, evodevo, is what I was attempting to copy with the title of my blog) looks at how mutations that change small aspects of how a foetus grows can have a relatively big impact on the end product.

        Duplication, such as what happened here, is often an important part of this process whichever area it influences. By making a copy of a gene then it doesn’t matter if any resulting changes have a bad effect since the original copy can take over functionality if the new version fails. This significantly decreases negative selection pressures allowing the gene to change in whatever way it wants.

        It’s worth noting that Dawkins is aware of all of this. The pause arises because this is the moment where he figured out that his interviewers were secretly creationists and he was trying to figure out how best to deal with them.

        Now I was faced with a dilemma. I was almost certain that these people had gained admittance to my house under false pretences — in other words, I had been set up. On the other hand, I am a naturally courteous person, especially in my own house, and these were guests from overseas. What should I do? I paused for a long time, trying to decide whether to throw them out, and, I have to admit, struggling not to lose my temper. Finally, I decided that I would ask them to leave, but I would do it in a polite way, explaining to them why. I then asked them to stop the tape, which they did.

      • I am not familiar with this organization, nor have I ever heard of them. If they obtained entry into Dawkin’s home under false pretenses, that is low, crass and most importantly, UN-Christ-like.

        That being said, and contrary to your assessment, he still did not have an answer to the question asked him, even after the pause and stopping of the tape and re-filming. He went on to explain that apes and humans are both modern creatures who share a common ancestor, but he could not furnish one example of the complexity of the genome increasing which was the question posed.

      • The lie appears to be more of one of omission, not mentioning they were creationists in order to get an interview with Dawkins (since he makes a point of not appearing on creationist programs). Whether that counts as unchristian or not I’ll leave for the Christians to decide.

        From what I can gather there was a conversation during whilst the tape was stopped in which Dawkins confronted them about his concerns and asked them to leave. Before they did they asked for just one last soundbite about evolution, so their trip will not have been for nought. Dawkins, being courteous, obliged. Hence the change in subject is not an evasion but of because of a change in context.

        As he himself writes

        “As it happens, my forthcoming book, Unweaving the Rainbow, has an entire chapter (‘The Genetic Book of the Dead’) devoted to a much more interesting version of the idea that natural selection gathers up information from the environment, and builds it into the genome. At the time of the interview, the book was almost finished (it is to be published in November, 1998). That chapter would have been in the forefront of my mind, and it is

        Having not read that book I can’t say whether it is as interesting as he claims it is, or whether it would’ve answered the question. However, he certainly does have the capacity to at least speak on the topic.

    • The ability to garner genetic information from neanderthal remains was simply the result of increasing technological ability. Whilst the remains they were obtained from were well preserved, there was nothing special about them. They didn’t discover a frozen neanderthal or something like that!

      As for the information question I think my response to Sepetjian’s Dawkins video covers it pretty well. However, if you want any more information (pardon the pun) on the subject I’d be happy to answer any further questions you have to the best of my ability.

      • Thanks Adam. I read your reply and did some googling and feel like I have a reasonable grip on the subject now. Well, reasonable for someone with huge gaps in my general knowledge of biology. That’s a fundy education for ya…

      • I once considered writing a few posts on basic evolutionary concepts but everybody seemed to already have a fairly good idea on how it works. I was going to finish this point with a moral of the story. I don’t know…don’t assume your audience knows what you do? But if you do assume that, why bother writing?

        Just assume I said something very deep there.

    • Those Creationists got me as well on their loony Creationist anti-abortion programme! But then I remembered that mutations can add information to a gene. So there you go :)

      • A creationist anti-abortion programme? That sounds fascinating. Whilst I know a bunch of them tend to be run by fundamentalist Christians (who also happen to be creationists) I wasn’t aware of any explicitly creationist anti-abortion material. What would it say “don’t have an abortion because you don’t have to worry about your child being some half ape/half human evolved abomination!”

      • It was actually quite depressing…it was abortion and cloning are wrong because Genesis gave us dominion over animals but not humans. Also, Rebekah’s unborn children were described as ‘children’ not fetuses, and some other stuff that is nothing to do with cloning/abortion and other arguments that had logic steps missing…I did a blog post on this because it was just ridiculous, it even made an analogy between slavery and abortion. And the creationism wasn’t really connected very well with the anti-abortion stuff. The programme might not have anti-abortion in every episode. It’s made by the Creationist Ministry (who make which is a misinformation conspiracy that propagates lies). Usually it’s fun to watch though, because they make so many mistakes in evolution theory and also in logic. So it’s good to chillax to. It’s on Revelations channel, I can’t remember what it’s called.

      • We don’t have dominion over mankind which is why you always see Christians oppose people being put in prison and having other liberties removed.

      • The first origin of life is still a murky area since these early forms leave next to no physical remains. Current thinking based off experimentation would suggest that out of proteins and DNA, proteins came first.

        RNA is a molecule similar to DNA but without the need for proteins – it can replicated by itself. It also has the potential to code for proteins, which would then enable the development for DNA.

        As such this RNA probably came first, it started to make proteins and then those proteins permitted the development of DNA proper.

      • The fact that you are furnishing one of them as the answer suggests that you do not realize you have a “chicken and an egg” problem here. You cannot produce DNA without protein and you cannot have protein unless you start with DNA.

        This is exactly the same conundrum we see with the termite. Termites chew on wood and they swallow it, but termites can’t digest it. It goes into their stomach and there’s little tiny critters in their intestines that actually digest the cellulose. Now those little critters can’t live without the termites and the termites can’t live without those critters. Which one evolved first?

        We see countless of observable examples of this in symbiotic relationships between flora and fauna the world over. Since they require and rely on each other for survival in perfect biological harmony, how could they have evolved separately?

      • Well like I said, RNA (or an RNA type molecule) could be what came before DNA, being able to code for stuff (including perhaps proteins) but not being reliant upon protein to reproduce. As such it removes the need for protein, knocking down the “x needs y which needs x” loop.

        Other similar situations may have similar answers. Like RNA not needing protein, so termites may not have originally needed their bacterial flora. Whilst I’m no termite expert, it doesn’t seem unreasonable to suggest that there was a point at which termites ate something they were capable of digesting and their bacteria existing neutrally within them, like our bacteria exists within us.

        Perhaps the termite changed to be able to consume the waste product of this bacteria, or the bacteria changed to produce a water product that the termite could consume. Either way, it would then have become beneficial for the termite to not wipe out that bacteria, instead allowing it to flourish.

        With this symbiotic, but not dependent, relationship in progress the potential for it to change further is there. Perhaps the bacteria was already capable of digesting wood, so immediately the termite could start moving onto it. Or maybe it was a more gradual process, with the bacteria opening up new dietary options slowly until it was the sole source of nutrition.

  2. So Lucy and Ardi wouldn’t have had the duplicates, I guess. But Homo Erectus would have. I saw once that there’s a theory that when humans didn’t need the huge jaw muscle that chimps have, the loss of this very thick muscle allowed the brain to grow in size.

    • Australopithecus afarensis (Lucy’s species) lived from 3.8-3 million years ago so the first duplication would’ve happened in them, provided they are our ancestors. Ardi lived >4 mya so would have lacked all the duplications.

      MHY16 is a gene responsible for developing strong jaw muscles. Humans have an inactivated copy leading to weaker muscles which, as you say, would seem to allow for larger brains. This mutation happened ~2.4 mya placing it during the time of early Homo.

      • Oh, so that would mean we got weaker jaw muscles quite late in our development, then, when we were already very estranged from chimps. So obviously the jaw muscle mutation was not the initiating factor in the development of our brains, or maybe not even that important, as it ocurred when our brains were already quite big and developed.

      • Actually the vast majority of our brain growth occurred in Homo erectus which lived after this jaw mutation. In the 4 my prior to H. erectus our brain had grown by ~200cc. However after they emerged (~1.9 mya) it grew by >400cc in only 1 my.

        Despite occurring relatively late in our evolutionary history the mutation for smaller jaw muscles likely still played an important role, although it was obviously not the only factor involved.

What do you think?


You are commenting using your account. Log Out / Change )

Twitter picture


Facebook photo


Connecting to %s