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.

Clever as a Fox

Sometimes we see things so often that we simply forget to ask “why are they like that?” For instance, let’s take a closer look at domestic animals. Dogs, cats, horses, cows, pigs – animals that we live with, and who couldn’t live without us.

Common Traits

What do all these domestic animals have in common?

pb_pup pb_cat pb_dog
pb_cow pb_horse pb_pig

Now this isn’t a particularly subtle example, but that’s kind of the point. You can see that all of these domestic animals have large white patches – they’ve lost pigment in their coats in some areas. Why do we care? Well, this is something that is extremely common among domesticated animals, but very rare among wild animals. I hear you saying “but what about zebras, or any other wild animal with white patches?”. What we’re referring to here is slightly different. A zebra will always have that patterning, whereas what we’re looking at here is depigmentation – the loss of color in certain areas in an animal that is “normally” colored.

What else is common among domestic animals but rare in the wild? Well, things like dwarf and giant varieties, floppy ears, and non-seasonal mating. Charles Darwin, in Chapter One of Origin of the Species noted that “not a single domestic animal can be named which has not in some country drooping ears”. A very significant observation when you consider that there is only a single wild animal with drooping ears – the elephant.

So perhaps something weird is going on here. Why do animals as different as cats and dogs have these common traits? It seems to arise simply from being around humans!

The Hypothesis

belyaev

The Russian geneticist Dmitri Belyaev provided a very interesting potential explanation. Genetics at the time was preoccupied with easily measurable traits that could be passed on – if you bred dogs, you could pick the biggest puppies, breed them, and they would produce bigger dogs on average. Fine. But that is selection of a single simple trait, something that likely did not require that many genes to “switch” in order for the puppies to be bigger.

But what if you were selecting for something more complicated? What if, instead of selecting for a simple trait like size or eye color, you selected for something more vague like behaviour – in this case, the very behaviour that made these animals more likely to be around humans. We can call it tamability, or lack of aggressiveness, or whatever – the point is, we are selecting for those animals who will behave in a manner we want around us. A wolf who does not display aggressive behaviour might be able to grab a few scraps of food from the garbage pile of a early human settlement, rather than being driven off.

And if we were selecting a complicated behaviour, rather than a simple trait, it seems likely that it will require more change in the animals genetic code. And since the genetic code is a tangled web where a small bit of DNA can be referenced in many areas of the body – perhaps selecting for a common behaviour would also cause other common traits to arise in animals that are otherwise different.

It’s like giving your car a paint job versus trying to make it go faster – the paint job is easy, but trying to make it faster could lead to your car exhibiting other traits you didn’t directly request, like consuming more gas during regular driving. This could be common across all your project cars. One is a low level trait (the paint, the size of puppy) that can be encompassed in a tiny bit of information (color, size), the other is a high level trait (speed, tamability) that must involve a wide variety of sub-systems changing as well.

The Experiment

Now if you were a Soviet scientist in the late 1950s, you probably worked on something awesome like a giant robot that shot nuclear missles, or a flying submarine. Not Dmitri Belyaev. No, he lost his job as head of the Department of Fur Animal Breeding at the Central Research Laboratory of Fur Breeding in Moscow in 1948 because he was committed to the theories of classical genetics rather than the very fashionable (and totally wrong) theories of Lysenkoism.

So instead, he started breeding foxes. Well, it was technically an experiment to study animal physiology, but that was more of a ruse to get his Lysenkoism-loving bosses off his back while he could study genetics and his theories of selecting for behaviour.

fox_1

He started out with 130 silver foxes. Like foxes in the wild, their ears are erect, the tail is low slung, and the fur is silver-black with a white tip on the tail. Tameness was selected for rigorously – only about 5% of males and 20% of females were allowed to breed each generation.

fox_2

At first, all foxes bred were classified as Class III foxes. They are tamer than the calmest farm-bred foxes, but flee from humans and will bite if stroked or handled.

fox_3

The next generation of foxes were deemed Class II foxes. Class II foxes will allow humans to pet them and pick them up, but do not show any emotionally friendly response to people. If you are a cat owner, you would call the experiment a success at this point.

fox_4

Later generations produced Class I foxes. They are eager to establish human contact, and will wag their tails and whine. Domesticated features were noted to occur with increasing frequency.

fox_5

Forty years after the start of the experiment, 70 to 80 percent of the foxes are now Class IE – the “domesticated elite”. When raised with humans, they are affectionate devoted animals, capable of forming strong bonds with their owner.

These “elite” foxes also exhibit domestic features such as depigmentation (1,646% increase in frequency), floppy ears (35% increase in frequency), short tails (6,900% increase in frequency), and other traits also seen frequently in domesticated animals.

The Results

Belyaevn passed away in 1985, but he was able to witness the early success of his hypothesis, that selecting for behaviour can cause cascading changes throughout the entire organism. For instance, the current explanation for the loss of pigment is that melanin (a compound that acts to color the coat of the animal) shares a common pathway with adrenaline (a compound that increases the “fight or flight” instinct of an animal). Reduction of adrenaline (by selecting for tame animals) inadvertently reduces melanin (causing the observed depigmentation effects).

So if Belyaevn is right, genetics is not just a low slow process that works on tiny incremental tweaks. Complicated environmental pressures can result in complicated genetic results, in a stunningly quick period of time. Where do I think we’re going with this?

Well, designer pets for one. Following the collapse of the Soviet Union, the project ran into serious financial trouble in the late 1990s. They had to cut down the amount of foxes drastically, and the project survived primarily on funding obtained from selling the tame foxes as exotic pets. Imagine a menagerie of dwarf exotic animals, who crave human attention and form bonds with people. It would be obscenely profitable.

And the out there thought for the day? We’re doing this to ourselves. We don’t encourage people to act aggressively all day to everyone they meet. We reward certain behaviours more than other behaviours. My unprovable conjecture? Humanity is selecting itself for certain behaviours, and the traits we think of as fundamentally human (loss of hair, retention of juvenile characteristics relative to primates) are a side effect of this self-selection.

Videos

Here are some great videos with footage of the tame foxes.

From NOVA – Dogs and More Dogs (starts at about 17:30)

“Suddenly, it all started to make sense. As Belyaev bred his foxes for tameness, over the generations their bodies began producing different levels of a whole range of hormones. These hormones, in turn, set off a cascade of changes that somehow triggered a surprising degree of genetic variation.

Just the simple act of selecting for tameness destabilized the genetic make up of these animals in such a way that all sorts of stuff that you would never normally see in a wild population suddenly appeared.” (Full transcript)