[MUSIC] Hello there. Welcome back. I expect you know that proteins are made of amino acids hooked end to end, like beads on a necklace. Proteins are the worker molecules of your cells. You're made of and by proteins. You have enzymes, tissue, skin are protein. Proteins make up the eye of a frog, the hair of a chimp, the scales of a fish. They're responsible for our distinctiveness, the fact that no two of us are alike. That's a reflection of the central dogma of course. We have different DNA sequences, so we end of with different sequences of amino acids in our proteins. Now these amino acid chains do not remain straight and orderly, they twist and they buckle, folding in upon themselves, the knobs of some amino acids nestling into the grooves in others, and that final shape enables proteins to accomplish their function in your body. Well that means that as far as proteins are concerned, shape if fate but the shape is function. You have about 20,000 different proteins inside each of your cells, and each protein has a different function, because it has a different shape. When the protein coding genes of a human are compared with the protein encoding genes of the chimpanzee, many of them are very similar. In fact, about 30% of our proteins are identical with those of a chimp and most proteins that differ do so by only one or two amino acid replacements, and that doesn't sound much, but don't underestimate the impact of a single amino acid change. Look at these illustrations of two proteins. In the first example, an alanine has been replaced by a glycine. Now, glycine and alanine are very similar. They're the two smallest amino acids you've got, and so the shape change is gonna be very small. Perhaps the enzyme that I mentioned in the last lecture that synthesizes some hormone is a little bit more or less active than it used to be, and from there you'd ask if this change makes the organism more or less likely to reproduce. But in the second example, alanine has been replaced by glutamic acid, and these two amino acids are very different because glutamic acid is larger, and it has a negative charge. So a protein shape is going to be completely different. It may well knock the enzyme out of business, or give it a whole new function, and if the enzyme is important then the organism could be in trouble. Alternatively, a whole new lifestyle could open up. Evolution is sometimes about small incremental changes, and sometimes it's about big lurching changes. Well, we actually don't know very much yet about the impact of changing a couple of amino acids on the functioning of most human and chimp proteins. But some of our proteins are obviously very different, and therefore are very interesting. So approximately ten protein coding genes known to be critical for brain size, have changed rapidly in humans. The best known, ununderstood example is ASPM, which is short for abnormal spindle like microcephaly associated protein, and that's why they call it ASPM. It regulates the number of times neuronal stem cells divide. The more times they divide, the bigger your brain. So in theory, if a single mutation popped up, that caused immature neurons prone to go one extra round of cell division. That could double the size of the cortex, and we know this gene was under going major changes just as our ancestors brains were rapidly expanding. We know how important ASPM is to brain size, cuz defects in the ASPM gene on people alive today are linked with microcephaly. Look at these pictures the brain on the left is normal and the brain on the right is someone with a mutation in the ASPM gene. The cortex is about the same size as that of an Australopithecus, one of our early ancestors. In fact, it's not much bigger than that of a chimp. So before we go any further looking at our genetic differences with apes, we actually need to address the key question. Why would we have a larger brain than a great ape. Even than a gorilla, that has a much larger body. The answer is going to identify the reason for a lot of our genetic differences with chimps, and according to many anthropologists, the answer probably comes down to the extreme energy cost of the primate brain. While the brain is 2% of the human body, it uses 25% of the calories we need to function each day. Our cerebral cortex is especially dense, it contains 16 billion neurons. It takes a lot of energy to support that. There may be some kind of evolutionary trade off between the science of the brain and the science of the body. There's a metabolic limitation, and primates can only consume enough calories to support one or the other. So the next logical question is, what allowed us to transcend this limitation and support this large brain? Well, Richard Wrangham in his 2009 book, Catching FIre: How Cooking Made Us Human, believes the answer is simple. Something you've probably never thought about. We cook. Cooking is essentially the act of using fire to pre digest food, and that's to get more energy out of the same amount of food. Of course cooked food is pre digested, that makes it softer, easier to chew, enables it to be able to be turned to mush in your mouth, which in turn allows it to be completely digested in your gut and in less time. In fact cooking food makes it yield about three times as many calories. So this is what allowed our brains to get bigger in a relatively short period of time. Cooking allowed us to support this large cerebral cortex, which in turn supports complex thoughts and complex societies. Fire makes living in large groups, how to form and maintain alliances. They had to track who owes what to whom, and keep alert to being misled by others in a group. There's a very clear correlation between the number of individuals in a group and the species average brain size, providing support for the idea that our big brains evolved to allow us to conduct complex social interactions. If our ancestors hadn't invented a way of extracting more energy out of the same foods, we'd have probably been stuck with the same size brain the great apes have, and small social groups. With our enlarged primate brain, we went rapidly from raw foods, to cooked foods, to culture, to agriculture, to civilization, to grocery stores, to refrigerators. All these things that now allow us to get all the calories we need in a day from a single sitting in a fast food restaurant. So what was once a solution now becomes a problem. Ironically we tried to solve it by going back to raw foods and eating our salads. So a conquest of fire was of critical importance. Mangum argues that our ancestor homoerectus, emerged about 2 million years ago as a result of this unique trait. Homoerectus developed via a smaller more efficient digestive tract, which freed up energy to enable larger brain growth. It also meant that homoerectus had a small pelvis, like ours, but it didn't have to support a big gut like a chimp's. But a thatmaller gut shows that cultural shifts alone are not gonna be sufficient to fully exploit these foods. Our predecessors had to adapt genetically to them. A lot of the genes that are most different between us and chimps reflect the way that, to a considerable extent, we control our own evolution. We used our big brains and the [INAUDIBLE] funds to mortify our environments, and then we gained genetic adaptations to fully exploit the new environments we created. Every new innovation led to new selective pressures, which in turn lead to more evolutionary changes. So okay, let's use hunting and cooking as themes. How did they select the genetic changes? Well, a lot of the regulatory mutants and gene sequence differences between us and chimps, affect the way we digest food, and that's not surprising if you consider how our diets have diverged from chimp diets. Chimps eat low energy food like leaves and fruits. We have supercharged amino acid metabolism for all that meat, and most of us have lots of salivary amylase genes. Amylase's digest starch. Chimps have only two amylase genes and we average six of them. So we produce a lot more amylase in our saliva. However populations that are never found, such as Australian Aborigines, don't have as many amalyse's as the rest of us. Showing that some of these extra amalyse's have been selected for since we took out growing vegetables and making breads. Our genes involved in smell and taste, present a nice case of how our genome provides some great stories. Mice have about 1,400 odor and taste receptor genes, and so do we, but where's their's are in good working order, about half ours are broken, because our ancestors didn't place much reliance on having a good sense of smell. Having these genes didn't affect our survival, so mutations could accumulate in them, and it didn't matter. It's use it or lose it in genetics. However, some of these null receptors that still work in us, have evolved rapidly, and acquired new functions. So we therefore smell things differently than a chimp. So what do you think we may like the smell of, that chimps do not? Cooked meats, more vegetarians are falling off the fence smelling bacon than anything else. To hunt meat and get that protein, leaves the hunters to coordinate their activities, and sophisticated language skills would have helped them and fostered innovation and invention leading to better tools, new ways to hunt and trap animals, and more comfortable homes. We also gossip about each other to work out amongst ourselves, who is good for what. Chimps can't talk like we do, because of differences in our vocal chords and nasal passages, but there are also neurological differences too. Some of which are the result of changes to what has been dubbed the language gene. It was first discovered in a British family with severe problems when it came to grammar and syntax. They also had problems making complex movements of the mouth and tongue, and in 2001, the problem was pinned on a mutation in the gene called FOXP2. In chimps and mice, the gene helped regulate the activity of genes involved in synchronizing jaw movements. In humans FOXP2 has acquired two mutations and turns on additional genes that have the job of synchronizing words. So our FOXP2 gene still synchronizes jaw movements, but now it has an additional job of synchronizing words. Don't you think it'd be fascinating to put the human gene into chimps and see what they can do with it? There are technical and ethical reasons there why we don't. Now, depending on how you calculate the rate of changes in chimps and humans, chimps may have changed more in physical and biological properties than we have. We appear to have evolved less, but a lot of our evolution has been about loss. We've lost our thick mat of body hair. We've lost our ability to survive well on raw food. We're so highly evolved now for eating cooked food, we cannot maintain reproductive fitness with raw food. There are a lot of deletions and pseudo genes in humans. The big story behind that is, you can achieve rapid deevolution, and particularly paedomorphism, by losing genes that would get you to the next developmental step, so that you retain the juvenile body. The most paedomorphic part of our bodies is our head. You remember the chimp skull with it's big jaw and sagittal crest. Well an adult chimp has a jaw so strong he could chomp your fingers off. We've got smaller weaker jaws, like a baby chimp. Now contributing to our weaker jaws are mutations in a gene called MYH16, that encodes a type of myosin muscle protein. MYH16 works exclusively in jaw muscles, and it gives the apes their powerful bite. Our MYH16 is inactive, so it's one of the pseudogenes I mentioned. This may have been what hominids looked like before it broke. This the skull of an early hominid called Paranthropus robustus. Now just look at those powerful jaws. Muscles connected those jaws through the zygomatic arches here all the way up to that sagittal crest. The sagittal crest is the enemy of big brains. It's best if you can have a sort of flattish sloping skull like this for the muscles to work properly. You've got big jaw muscles, you want a flattish scalp and you want thick jaw bones. So I fix skull bones to resist the pressure of those muscles, otherwise the muscles could crack the skull. If you lose those muscles, you don't need the sagittal crest, and you'll get a big dome skull to put a big brain in. So Paranthropus is believed to have, eaten a lot of plant type roots, and they're very tough to chew on. A change of diet, aided by the use of fire, probably meant we could deal without such a strong bite. Well, we talked about Paula Allard's work on human accelerated regions, in the earlier lecture. She showed that regulatory alterations underlie interesting evolutionary differences in us and chimps. Well, Gill Bejerano and David Kingsley, they led a group of researchers at Stanford who reported in 2011 that 510 regulatory regions conserved in chimps, monkeys, and mice, are lost in us, and many of these are involved in steroid hormone signaling and neural function. Well you may have heard of steroid hormones as those things that can get you chucked out of the Olympic Games. Better to think of steroids as a class of hormones that coordinate a lot of our life processes. Now we can have a lot to say about, the stress hormone cortisol in a later lecture, but now we'll look at another steroid hormone called testosterone, and testosterone is gonna go through the body, telling all the cells they're in a masculine body, and to act accordingly. It does this by binding to a receptor, that then turns on genes. Now we used to think that all you need to know about hormones is how much of a hormone is in the blood stream, but you also need to know about how many receptors you have and where they are distributed. Mutations in receptors can have a big impact. So it turns out we don't have sensory whiskers coming of our cheeks like a cat, and we don't have penal spines because we've lost regulatory switches from the testosterone receptor gene, and what you're looking at here is a cat's penis. One of the ugliest objects know to man, those little white, pointy projections on this penis, they're the penile spines, and we're one of the very few mammals who don't actually have them. Chimps have smaller, thinner penises than we do. Unlike the cat, they're covered in these small, pointy projections made of keratin. The same material as hair or nails. Now it has these because it expresses the gene for testosterone receptor in its penis. Likewise a chimp like a cat has sensory whiskers on its cheeks. We lack this because we are missing regulatory DNA that switches on the testosterone receptor gene in our cheeks and penis. We still have intact regulatory regions that turn on the testosterone receptor in our brains and testicles, we've lost other pieces of regulatory DNA that would get the receptor produced in our cheeks and penis. Imagine you have five switches, and each switch turned on the light bulb in a different place, and you took one of those switches away the light would still work in four rooms, but it wouldn't work in the fifth. No one is sure what purpose the spines serve, a bumpy penis, maybe better removing another male sperm, and we're much more monogamous than chimps, so that service may no longer be required in us. So it's been suggested that these penile spines, these bumps, may abrade the vagina of a chimp, make sex painful and put them off having sex with other males. But then you think of ribbed condoms and bump laden vibrators, that doesn't quite make sense does it?
