Human Evolution and Frameshift Mutations

How did humans evolve from early primates? How did “human like” traits such as a smaller jaw relative to apes and hairlessness pop up when they don’t appear in the wild in any real frequency? The typical explanation for why humans have smaller jaws than early primates is that our diets changed and our brains got bigger, pressures that caused a smaller jaw. But there’s another way to look at this – what if our diets changed and our brains got bigger due to proto-human society dealing and adapting to an increasingly frequent and nearly catastrophic mutation of the jaw?

Myosin Heavy Chain 16

The human and chimpanzee genomes have both been mapped, so we are able to make comparisons between them. This is extremely useful, as chimpanzees and humans shared a common ancestor, but genetic lines split apart approximately 7 million years ago. So examining the differences may tell us something about how humans evolved.

myosin

There is a protein called myosin heavy chain 16 (aka MYH16) which in chimpanzees and other non-human primates is expressed almost exclusively in their powerful jaw muscles. These strong jaws are an adult trait – a logically complex one that would be more sensitive to random mutations.

And that’s exactly what seems to have happened. Non-human primates have DNA that codes for the complete MYH16 protein. The corresponding part of human DNA is missing a random chunk – which causes a frameshift mutation.

Frameshift Mutations

What is a frameshift mutation? Well, first let’s find out how we build proteins. We have a strand of messenger RNA (imagine a long tape with letters on it) which a ribosome (hell, imagine a tiny elf) uses to produce proteins. The critical thing to consider is that a ribosome builds a protein by reading three nucleotides at a time, and these three nucleotides code for a certain amino acid. These amino acids are chained together to produce proteins. Some combinations of three nucleotides can also act as “punctuation marks”.

"Wait, did you say there's three million more pages after this?"

So our wee elf looks closely at the long tape of letters, and starts off with the first three. His “frame”, the little chunk he works on, is three letters long. This frame is an instruction to build a certain amino acid, which he makes. He then goes along the tape, three letters at a time, making an amino acid each time that he sticks onto the last. This will eventually create a long chain of amino acids that we call a protein. But each frame doesn’t need to code for just an amino acid – it can also code for other instructions (those “punctuation marks”) starting or stopping this chaining process.

Now you may have guessed what a frameshift mutation is by now – it’s where a single letter in our tape disappears, or a new random one gets thrown in, causing our frame to get shifted slightly. This means that the resulting triplets after this error will be horribly wrong. It’s like the difference between

HEY MAN HOW ARE YOU BRO and
HEY MAN HWA REY OUB RO_ or HEY MAN HOQ WAR EYO UBR O__

if one were to speak in sentences containing only three letter words. The first sentence makes sense if we parse three letters at a time. The two others have a random letter removed, and a random letter added in. If we parse them three letters at a time, the sentence turns into garbage halfway through! The resulting nonsense (or malformed protein) is a result of a random insertion or deletion of information (nucleotides) and our “frame”, the manner in which we interpret it.

Consequences

So a frameshift mutation occured in early humans that affected the production of the protein MYH16. This protein is involved in the strong powerful jaws that primates have, but not humans. We often think of mutations as a simple little “blip” in the genetic code, but the way our bodies parse this code can cause cascading effects. Instead of MYH16 having a slightly different amino acid in a random spot from a random mutation, the specified amino acids after the mutation will change completely!

So you might think that we’ll have some odd protein that’s mostly normal, and the parts after the mutation affected by the frameshift will be wonky. But – and this is an important but – the triplets code for “punctuation marks” too, remember? In this MYH16 mutation, it turns out that this frameshift caused a punctuation mark (aka a stop codon) to just pop up – so the protein is cut off far sooner than it should be! Not too good for any traits relying on that protein.

Look at the differences between these gorilla and human skulls below. The large bony ridges on the gorilla skull on the left are where the larger jaw muscles attach – otherwise they would literally tear off of the skull. You can also see how the gorilla skull seems “empty” on the sides – that’s because it is filled with large jaw muscles, reducing space available for the brain. The red tinted parts are where the jaw muscles attach – you can see how much more “anchoring” a gorilla’s jaw muscle requires.

human_gorilla_skulls

And this is where it gets interesting. This mutation in our human ancestors happened approximately 2.4 million years ago. Right before our ancestors stopped looking like primates and started looking like us. If you lacked the protein that operated a powerful jaw muscle, you could not carry a large jawbone around and use it effectively. If you can’t carry a large jawbone around, there is strong selection pressure for those with smaller jaws to survive. If your jaw gets smaller, then the loading of the jaw on the skull decreases – bony ridges disappear, and the skull can get larger and lighter since it doesn’t need to be as strong. A larger and lighter skull can accommodate a bigger brain.

It appears that a random mutation, flipping a single bit of genetic information, has beautifully complex cascading results. Viewing the world as a hostile agent of noise and fury, winding down to an eventual death by entropy is wrong. You can fold a piece of paper, give it to a child, and have them cut crude holes in it with cheap scissors – and when you unfold it, the snowflake is beautiful.

So too can randomness be folded and twisted by logical structures in biology and physics – and the result is our amazing world.

Chimpanzees and Neoteny

One of the biggest “human” questions is “where did we come from?”. While the mechanisms of evolution are well established, the route humanity took to get to its present state is not as well detemined. It’s the difference between knowing the rules of chess and being able to figure out the personality and play style of a grandmaster from a few snapshots of a very long game in progress.

One proposed mechanism for the evolution of humans from primates is neoteny, where juvenile traits are retained and adult adaptations lost. This has been observed in foxes subject to behavioural selection. For instance, look at this young chimpanzee.

naef_fig4_baby

This picture is from a 1926 study by the German anthropologist Adolf Naef. He describes it as “the the most human-like picture of an animal, of any that is known to me.” The little guy does seem to have a rather regal and refined air about him, but we can’t just wave our hands and call it case closed at this point. Can we look at the development of a chimpanzee and see if there are any quantifiable parallels?

Bone structure is a great place to start. Chimpanzees, like humans, have a skeleton that changes shape and size as the organism matures.

chimp_human_compare

The two skulls on the far left are those of an infant chimpanzee (top) and an infant human (bottom). Bone structure and shape are very similar, with the classic huge head and tiny cute face we seem programmed to love. The two skulls in the middle are of a adolescent chimpanzee (top) and an adult human (bottom). We can see the jaw start to lengthen in both, and their overall similarity. The final picture on the top right is of an adult chimpanzee, who has a significantly larger and more powerful bite than any adult human.

So what does this show us? Well, humans and chimpanzees appear to have very similar development in terms of bone structure as they grow up, except that humans just seem to… stop at a certain point. There are a multitude of theories as to why this happens, but they all seem to follow the pattern of certain behaviours being selected for which affect the balance of hormones in the body that control the development of adult features. This is called neoteny.

Now neoteny doesn’t mean that every single part of the entire animal becomes more juvenile, or that the animal becomes less complex overall. It’s a selective reduction in complexity – traits that appear later in the animals development (ie adolescence) become less likely to appear.

So how did humans get their unique features? It’s very difficult to select for traits like a bigger brain or hairlessness when those traits don’t appear in the wild in any real frequency to begin with. Viewing human evolution through this lens seems to indicate that change would be very slow, and very hard to do.

chimp_dental

But what if instead of selecting for a simple trait, we (or the species as a whole) selects for a behaviour? The neat thing about selecting for this is that hormones have a strong influence on behaviour. So we are partly selecting for certain hormone levels or actions. These hormones also share logical relationships with other hormones, and act in many different parts of the body, not just the parts of the brain influencing behaviour.

If we put significant selection pressure on a species, we are effectively increasing the mutation rate (ie “mutant” creatures tend to be selected more). Increases in mutation rates would be more likely to affect more logically complex proteins arising later in life involved in the development of adolescent features (due to more references to more parts of the mutating DNA) rather than less logically complex proteins that would be involved in juvenile features.

As a result, we now have a mechanism for how these bizarre traits that we simply don’t see in the wild can become so common, so quickly, and also a predicted side effect – neoteny.

But how could this end up as an advantage? It seems that mutations are destroying those adult adaptations that made the organism successful in the first place. But what if the world changes simply because you and others like you live in it? We like to think of physical strength as the be all and end all of “dominance”, but I think this is only true if you’re “one chimp against the world”. A chimp who can more accurately figure out social structure and how to manipulate his place in it could be far more successful in breeding than a chimp who is simply stronger than average.

A chimpanzee’s ability to learn is drastically reduced upon reaching maturity. But baby chimps…

babymimic

Baby chimps will eagerly mimic a human caretaker – sticking out their tongues, opening their mouth wide, or making their best effort at a kissy face. Not only is the basic mechanism of learning there (imitation), it appears to be very focused on social relationship. And this ability decreases with age! It seems that the retention of juvenile traits is not the burden it appears at first.

So the origin of humanity? Well, it’s still up in the air. But I think it’s incredibly likely that we literally changed ourselves – that living together created environmental pressures (namely social ones) that selected for behaviour in an incredibly complex manner, where the ability to learn and social skills were valued and led to reproductive success. All too often we look for outside pressures in evolution, when some of the most magnificent examples (like the plumage and mating rituals of birds of paradise) are simply a result of everyone agreeing to play an elaborate game.