Evolution of Bipedality, Human Pelvis, Muscle & Brain | Terence Capellini | 258

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Also. Thank you for joining me.

>> Thanks for having me. I'm glad to be here.

>> Can you start off by just telling everyone a little bit about who you are and what you study?

>> Yeah. So, I'm a professor and chair of the department of human evolutionary biology at Harvard. Uh, I study developmental genetics and how that relates to the evolution of the human human body, particularly the human skeleton.

>> And so at at a basic level, how do you generally go about studying that?

>> Uh that's a good question. So the we we take a very u multi-acceted approach in my lab. So the idea is we're trying to understand where in the human genome are the genetic changes that generated the unique human body form particularly our ability to walk on two legs, our ability to throw, you know, our big brains. And um to do that we can scan the genomes and try to uh understand the human genome as it compares directly to say the chimpanzeee genome our closest relatives uh or the gorilla genome a more distant relative. But that gives us lots of DNA changes that really don't make any sense. Uh so what we need to do is provide context for them. So what we do is we look at the phenotype the observable physical traits that we're trying to understand. So for instance uh looking at the pelvis between humans and chimpanzees and understanding where in the pelvis are the changes uh the anatomical changes um that have occurred in human evolution to make us walk on two legs. And so we can use phenotyping data on the pelvis and how it how it forms uh and on humans and other primates to get comparative um you know contextual information. Uh and that gives us the phenotyping side and we have the genetic side but really what we want to do is link the two. So we have to bring in a bunch of other types of data. So those data include functional genomics. So tools that we have now to assess what what genes uh what regulatory regions for genes are used in cells during development to to to sculpt the morphology that we see in the adult. Uh so we bring in functional genomic techniques. Uh we bring in comparative sequence analyses. We do functional experiments in the wet lab where we can modify cells or the mouse model to look at changes and how they affect the phenotype. So to bridge the the genotype or the genetic sequences to the phenotype, the observable differences, we bring all these different tools and and and and one thing I'll say is um we believe that when we're developing a hypothesis or a model of of how evolution occurred, how how the genotype connects to the phenotype, we have to bring in as much different types of data as possible. And if we do this correctly, it only supports the model. If if we generate data and it does not support the model, well, we don't throw out the data. We actually change our model. We have to think differently about how we approach the question first and generate new hypothesis. So, we're really about trying to understand um how you build a model with existing data and new data that you can generate to to connect um the genetics to the traits that we're interested in in human evolution.

>> Yeah. And I think one of the things that you said that's important there is you can't merely look at the DNA and compare the DNA of different creatures and learn much of anything. Like you know if we want to understand how humans walked on two legs and how we got there compared to our ape ancestors, we can't just bring up the chimp genome, bring up the human genome, know that they have a different pelvis and a different sort of muscularkeeletal anatomy and just look up the answer. um we have to know something about how the development of the organism actually happens. How does how is the pelvis and the legs and the muscles, how are they constructed in a human differently than a chimp and how do the genes actually change in a way that changes that sculpting and construction process. So you can't just look it up in the raw genomic sequence. You need to you need to know more about the animal, its ecology, what was what was driving, you know, the pressure to move a certain way and then literally how the animal is built in an embryionic sense.

>> Yeah. No, exactly. And and so when you look at the human genome and compare it to the chimpanzeee genome, there's three billion base pairs, right, that are that are that you can find that you can look and see. And um and when you actually and that's in the hloid genome, um it's six billion in the dloid genome. And so what you have to do is kind of filter those base pairs. You have to figure out a way to narrow down to the the more important ones. And that's where these tools like functional genomics come in. So you can take developing cells of a of of of an embryo, a human embryo or a mouse embryo, and you can identify in those cells, if they're from parts of the pelvis, what genes are turned on and what regulatory sequences switches are are used. And then when you have the switches and the genes that are turned on to to sculpt the pelvis, you can then narrow in on those genes and those regulatory elements and look where are the changes between humans and chimpanzees and those elements and you can further refine and refine as you get closer to where you think the targets are for evolution. And that's a more involved um part, but well, I'm sure we'll get into that today.

>> Yeah. And so, you know, a lot of people are interested in human evolution, obviously, because we're humans. And there's a lot that makes humans unique or at least different in important ways. There's a number of them we could talk about. We'll probably have time to talk about some of them. One of them obviously is our big heads, which in case are big brains. Maybe we'll get to that. But another one is our muscularkeeletal system. And there's two really interesting things about our muscular skeletal system that I think we'll talk about today. One is the fact that we walk upright. We are bipeedal and that's a key differentiator for our lineage compared to most other animals that are still alive today and not extinct. And then the other one is um sort of our limbs and muscles more generally, especially as it relates to things like throwing and and using our arms for for that type of motion. Obviously, the dexterity of our dexterity of our hands and our grasping and writing abilities and all that. But you've done work recently on the evolution of bipedality. And so I want to talk about that first. Let's set the stage here by thinking in terms of sort of the why and the what before we get to the how. So obviously at some point some creatures started walking on two legs at least some of the time and then eventually you know you get humans and we pretty much walk on two legs all of the time once we learn how to do it as as little babies. When roughly did bipidality evolve and become you know common place when in what part of our history in our lineage was that the common mode of locomotion? Is this a million years old or or deeper? When did this happen?

>> Yeah. So that's a kind of a controversial qu question in some regards because um we we we have we know that humans and chimpanzees shared a common ancestor between 6 and 8 million years ago. And the argument is that the common ancestor uh probably look more like a chimpanzeee or a gorilla. And that's because chimpanzees and gorillas as African apes and our closest um you know living relatives um are are those that have particular types of locomotion that are common between the two that is knuckle walking. Uh they are generally semi-upright. Uh they rely on longer forlims than their hind limbs. Uh longer arms and legs. uh they they rest their a lot of their mass on their on their on their on their front digits on their hands and they propel themselves that way with their with their hind limbs u pushing them forward as well. They also sp spend the time spend some time in the trees. Chimezes spend a lot more times in the trees than than gorillas, especially big gorillas that are mostly uh terrestrial. And and so they share the two two types of African apes share this common locomotive pattern. And by the rule of parsimony, you know, you expect that the last common ancestor was probably like a knuckle walking uh animal that then eventually stood upright. Some people argue that's maybe not the case. Some people would argue that um the earliest uh earliest forms of of humans might have been already more upright because they might have been more suspensory. That is they they use their arms to hang down from trees. Uh and therefore they're they're moving um more below the branch uh rather than coming down to the ground that often. And and if they came down to the ground, maybe then they would use their legs to walk more bipedally. So there's been some debate about how far you can push back the origins of bipedality based on which model you follow.

>> So more like a like a gibbon if we imagine a gibbon it that hangs from branches and you know was was the some of the earlier predecessors humans was it more like a gibbon or more like a chimp? That's basically what we're talking about here.

>> Yeah. So some Yeah. Exactly. So so gibbons are are Asian apes. They're the the the oldest living um relative to to to humans. uh they they diverged quite some time ago uh in the Mayene early early in the Mayene um you know close to I believe 22 million years ago if not later and um you know these these forms uh are long arms they're the brachiatators they're the animals that you when you look at in when you go to a zoo they're the primates that really move quickly under the branch they very long forlims very short high limbs and and they can walk upright um they don't do it all the time but when they do their long arm arms have to hang above their bodies as they walk on two legs. Now, other primates like like gorillas and chimpanzees can also walk by pedi. They just don't do it that often. They do it in particular contexts like if they're waiting in water or if they're um you know trying to carry some things or if they're becoming threat making threat postures, right? They'll stand up and move move around like that. So there's some evidence in the living primates that bipedality could have occurred. And that makes people believe that maybe bipidality was a little more common in the in the fossil record. And of course, you know, I'll just like pause here and just kind of preface that all of our models are based on living humans, which are bipeds, and living apes that have their own specialized locomotive patterns. And there's a diversity of locomotive patterns that exists in the fossil record that may not be evident or modeled by living forms, right? And we have to be careful about how much we rely on modern forms. The crown the crown the the distal tips of branches on a phlogenetic tree if you're interested in phogyny as being informative of what happens at a node where the where where the common would be where they spread.

>> Yeah. We only see obviously what's present today. we only see a small portion of what was present in the past because we only dig up so many fossils and they're really hard to find. And also we often, you know, we can show many examples in in the tree of life that we do know about where, you know, creatures had features back in the day that we don't really see today. And so if you're basically saying we need to be careful and not be too um present day centric in our thinking and our hypothesizing you know there could have been creatures I guess you know ape-like creatures that maybe walked on branches in the trees and maybe they had gibbon-like arms but also were kind of bipeedal and and just stuff we haven't thought about yet.

>> Yeah. Exactly. and and and so um the other part to consider in all this and I know I haven't gotten to answer your question yet about when bipidality arose but the other part to consider is that uh species and their morphologies can sometimes change pretty rapidly. Uh and so the idea that if African apes shared knuckle walking and that was what the last common ancestor could look like, it's very possible that um the last common ancestor didn't look like that. looked more like a biped and both African apes converged on the same morphology, the same shape, the same locomotive practice. They both gained knuckle walking independently. Uh and that really depends on what happens in the fossil specimens in fossil species that are existing um around that time. And so so so you can get convergence of biology. You can also have um shared homology or the fact that okay if you think that humans um diverged from a knuckle walking ancestor that kind of makes sense because you chimpanzees and grills had that shared biology and therefore humans diverged and created a new form of locomotion. So there's both um convergence uh and there's also um homology uh shared shared ancestry that drives the kind of biology of what we think about and we have to use those kind of concepts to ha to think about how we reconstruct the last common ancestor of humans and chimps and the changes that led to humans to become bipedal.

>> So you know there there's some controversy with this stuff and there often is in the in the paleo world just because the fossil record is always so imperfect. But if we define bipedality to be um having an anatomy that would enable bipeedal locomotion to be the primary mode of locomotion for a creature in the past. What is our best current guess today as to when we had something like a human or an archaic ape of some kind that had the ability anatomically speaking to primarily get around through bipeedal locomotion?

>> Yeah, that's great. So that that's called obligate bipedalism. uh as opposed to facultative where you might do it temporarily. Uh and I would say oropycus apherenis Lucy has pretty clear signs of being a biped and likely an obligate biped. So that would be around 3 and a half million years ago.

>> Mhm.

>> The fossil forms that occurred before Lucy Oropus Apharenis for instance artipythecus raidus which dates to around 4.5 million years ago from Africa East Africa their their pelvis and their knees their feet suggest kind of a mosaic like pattern of locomotion where they probably could walk on two legs fairly well but they didn't do it all the time probably spent some time in the trees and one of the pieces of evidence is that they have a big toe that's that's separate from the rest of the digits. It's appendable. Uh whereas humans have the big toe that's in aligned with the rest of the digits, making us a good walker.

>> Uh so artipythecus has some traits that may really clearly show that it could probably walk um on on the ground or in the trees. Uh but locomote not necessarily as an obligate biped.

>> See around 3 3.5 3.3 we see evidence of more oblig obligatory bipedalism in the fossil record. So roughly speaking, if you go halfway in between humans today and our last common ancestor with chimps, around that time, there were things that probably could walk on two legs quite a bit.

>> Yeah. Yeah. And so so interestingly enough, um the the development of bipedalism uh in in early hominins, the the forms that would give rise to eventually humans. Um and that's a large group of organisms now that we know that existed between uh six and and 2 million years ago. There's there's lots of those forms of hominins that look like they could walk bipedally. Uh and so um if you think about this, I'm going to digress for a second. Evolutionarily speaking, bats acquired at one point wings that allowed them to fly. And the bat wing is considered an evolutionary novelty. It really facilitated um a new form of locomotion that let let these the ancestors of bats and bats themselves to go across the world and occupy new niches and we call that an adaptive radiation.

>> So there's no other mammals literally flying around and able to occupy that part of the natural world and so they had a really strong competitive advantage and they could really exploit that and and diversify a lot very quickly.

>> Exactly. And so some people argue that the earliest changes in bipedalism did the same that there are now forms of hominins like oralopythecus apherenzis paranthropus another um another lineage of hominins artipythesines all of these forms that could walk somewhat on on on on two legs. Some more obligatory and others more facultitative. But that set up a new adaptive radiation, a new way to get around the landscape that in some ways out competed other forms or allowed them to exploit new niches that other forms could not could not.

>> Okay. So, so we've we've touched on the when a few million years ago there was creatures starting to walk around bipedally more.

>> Now we're getting into the why. Like what what was the selective pressure? What was the advantage that was opened up by being able to move around in this way? I want to dig into that more. Before we do, so you've already mentioned that we had oralopythecus, a different genus than homo that was probably using bipedal locomotion. What's the difference between oralopycus and homo? Would we consider these to be protohumans but not quite human in the full sense? Can you just explain that difference?

>> They're

>> Yeah, socus is a group of of hominins that they basically from 3.8 8 to roughly like 2.5 million years ago, depending on who you ask and and the definitions are dependent on on morphology and how you define morphology. But this group of this group of um organisms had the ability to to walk on two legs. But they had very small brain sizes. They had brain sizes about the size of a chimp, maybe a little larger. So 300 400 cubic centimeters. In comparison, human brains are 1500 cubic centimeters if not larger. Uh and so um these forms of hominins um are distinguished from from humans really based on other traits like for instance enlarged brain size or the incre the the kind of changes in body proportions that come with um becoming not just an obligate bi biped but a good bipedal now that can use can run uh and walk long distances and really get good stride lengths. So having long long legs compared to arms. Uh these oropithesines didn't have that. They had about equal sized um limb proportions. Um you know, forlims and high limbs were about the same size. In comparison grills and chimpanzees have very long arms compared to their legs. Right? So you're you're moving in in space and time to a group of organisms that are upright. They're they're facultitative to obligate bipeds. They're doing it fairly well, but they're not efficient like you modern humans are. and Homo start to acquire really um the body proportions of modern humans, the brain size of modern humans, a lot more dexterity in the hands and feet in the feet losing the dexterity and gaining a a big toe.

>> And also Homo's got association with stone tools and cultural aspects that we not necessarily see in early aopithesines even though there's some rudimentary tools with

>> Austral. So by the time we get homo on the scene certainly, but by the time we have obligate bipeds that are good at getting around on two legs, what you know, thinking about the why question here, what is bipedality buying you as opposed to being able to walk around on four legs? Can you physically go into different types of environments that you couldn't before? Is there some kind of energetic or physiological advantage or disadvantage that being bipeedal gives you compared to being a four-legged animal?

>> Uh yeah. So I think this gets to the to more of the why question and and this is related to more of the you know you can ask why on the ultimate sense and the approximate sense and you know at the time of the of the of basically the pyoplya scene which is the window of time we're talking about you know between six and and 2 million years ago we're really looking at this window of time um climate change is occurring and the earth is actually getting a bit cooler uh and as the earth is cooling these tropical lush fars in parts of Africa are becoming smaller. Uh they're slightly getting they're reducing in their size and they're transitioning from these tropical woodland plants to more wooded vegetation that it's more patchy forests. So you're getting um forests, but they're shrinking in size and becoming more patchy from one one one forest to the next. And so that opens up tracks of land in between the forests. And animals actually need to to move from one forest environment to the other. Or they don't. They just stay in the forest environment that they're in. And so one could argue that chimpanzees and gorillas pro probably so efficient at what they've done that they stayed in the tropical forest environments that were changing the least. uh and but these other hominins that arose uh began to exploit this new environmental o opening this uh new area between the forests and having to tra traverse between one forest to the next potentially to collect resources um potentially to because they were pushed out by competition from other forms. Uh we don't know the exact answer but being able to walk on two legs gave them more efficiency to move between between forest environments. It it also allowed them to carry objects uh in a very efficient way, carry offspring. Um you know, primates carry offspring, cling on to them. So, I'm not sure if that would be a very big advantage. Um but maybe carrying other objects might have been. Uh being tall and being able to see over the savannah grasslands that are occurring at the time may allow them to look and and see over the grass so they don't stumble upon a predator or can avoid predation. Uh see distance as well. And then there's the argument that some people make that being more linear, being tall and linear, uh, changes the the the way sunlight hits the body and that might have reduced um the the heat load that's generated on the body over time.

>> What's clear is that um, and this is again based on models of living forms, right? That modern humans when we when we walk, we do it very efficiently. And if you take a chimpanzeee and you say walk and you put them on a treadmill and try to make them walk, they don't do it efficiently. Well, that's kind of not fair uh because they don't typically walk that way. But it does suggest that human walking is more efficient than chimpanzeee walking and it's more efficient than chimpanzeee walking on all fours. Uh so there seems to be uh decreased um you know oxygen use and consumption and more and less energetics less energy consumption involved in human walking than other forms and that might have that's a modern thing right modern humans are walking and we're very efficient. uh how you model that to look at the the earliest time is difficult but must have been some energetics like advantage and I say energetics because when we think about evolution we often forget that it's really about energy and how we use energy and how we distribute energy to development reproductive reproduction growth and homeostasis fighting disease and you only have so much energy in your body and almost energy availability it would have been important for early humans to exploit um to acquire energy through diet and and and um and exploiting new resources and not use a lot of energy to to do so.

>> So

>> yeah. Yeah. And I think implicit in some of the things you were saying is that you know a lot of these advantages to bipedal locomotion and related adaptations like being taller. They make a lot of sense if the forest our ancestors were dwelling in became sparser or patchier. um because you got to go, you know, maybe you want to get from one patch of woods to another, but there's a grassland in between. That's only going to those things are only going to be advantageous if the forest is going away or you're moving into a more grasslandike environment or something like this. When these adaptations were arising and we're start we start seeing bipidality become more common in Australopythecus and in early Homo, is there also evidence in the fossil record that the climate was changing, the grasslands were expanding, the forests were getting sparser and that type of thing?

>> Yeah, there there is there's changes in the plant life. So people uh do paleoecological reconstructions. They reconstruct the past uh pale ecology based on what they find in in the fossil record. They can find you know fossilized plants that have particular morphologies that are coincident with either being in a tropical forest or a wooded environment. Um they can also look at isotopes and isotopes um accumulate uh and and and change in in according to the different plant species that are out there. Um there's shifts in carbon isotopes that tell um um tell researchers that the climate is getting more cool that the plants are getting more grass-like rather as opposed to tropical vegetation. Um and they can look at those ratios of particular um of isotopes to really understand how the climate is is changing. And then of course they can also look at um uh sediment sediments themselves to identify the types of um windblown sediments that are present in a in in a in a core from a ground and that might tell them something about wind patterns uh and temperature uh and and and what what was in the actual um uh environment at the time.

>> So

>> I see. So so the environment would have been changing in some way like this. It opened up the opportunity for bipedal locomotion to then offer an advantage if you start evolving it. And despite any patchiness and gaps in the fossil record, you know, at some point there was something like a knuckle walking ape. And at some point there was an oralopiththesine that was more of a mosaic that probably walked upright sometime more than a chimp but not all the time like us. And eventually you do get to you know really good bipeedal locomotion by the time of early homo and it offers certain advantages. We've gone over some of those. So so we sort of understand the why part of it you know to a reasonable extent. We know roughly when this was happening and we've got a you know a decent picture of the timeline it sounds like and obviously it did happen like we walk on two legs and and somehow we got here. What are the sort of anatomic changes that needed to happen to make this possible? So, for example, you know, the the bones and the anatomy of a chimp are such that, you know, the chimp can't walk upright all day long if even if it wanted to. The the physical change, what are the physical changes to the hips, the legs that needed to start to happen in order to to enable something like us to walk around on two feet all the time?

>> That's great. Great question. So, you know, the um the bipedality is really a full a full body trait. It's a really it really affects the entire body. Uh so when you look at something like an African ape, uh they are they're knuckle walkers. So their center of mass is far forward. Um when they walk on uh on their, you know, when they use their forlims to to knuckle walk, their center of mass is forward. And so as a result, their rib cage, for instance, is deep from front to back. Uh, and their arms are long cuz they they support their weight on their on their knuckles. Uh, and they have long forlims. Their hind limbs are shorter. Uh, and their pelvis, um, the the classic pelvis, you know, that you would see in a human is not present in a chimpanzeee or gorilla. Now, the pelvis has a number of different changes. um in the pelvis in primates that are not human, non-human primates uh generally have um the upper part called the ilia. Uh and the ilia are these blades that you see uh that that stand upright. So the way to think about this is that if I was standing behind you and I had my hands on your back about the side place where your kidneys are, that's where their pelvic ilia would be and they would sit exactly in that plane with my hands on your back. That's called a coronal plane. uh crown loop because it's like a crown across your head. So they sit in that same plane and they're flat and they're tall uh and they're narrow uh um from from from side to side. They're narrow. So um these ilia support big muscles in the back called the glutial muscles that push that anchor to the back of the um the um the femur and they actually push the leg forward when they when they when they contract. And uh in humans, the pelvis ilia have actually been shortened drastically. They're short and instead of being uh short and narrow and sitting on the back, they're actually short and wide and they sit on the sides of the body. So they've been curved around the body. The classic, in fact, the word pelvis is Latin for basin. And so the earliest an anatomists who were looking who were describing these phenotypes you know were were calling a pelvis based on the human form. But the human form is very unique. Uh the the human form has these unique ilia that curve around the sides of the body. Uh whereas all the other forms actually have more of these flatbladed like structures. And so when the ilia got short and curved and around the body, the muscles that I talked about, the glutius muscles that are typically on the back, well, one of them called the glutius maximus stays on the back. We still have that. That's our butt muscles, you know, uh, and we use that when we walk and run. Uh, but two of them, glutius minimus medius, have curved around the sides of the body. So having muscles that are now positioned not on the back but on the sides of the body allows for us when we walk to stabilize oursel. So what do I mean by that? Well, when we take a step and we're off the ground, we could fall over because we're on one leg and these muscles pull us back down. They contract and pull our bodies back down to stable.

>> So So if a chimp is walking upright, they're literally easier to push over because they don't have this kind of muscular.

>> They don't have a lateral They don't have the lateral stabilizers. In fact, when a chimp walks upright, they do so with a bent knee and a bent hip.

>> So, they actually are very flexed and low to the ground. Uh whereas like in humans, we have a straight knee and straight hip. And when we walk, we just walk, you know, we just walk like a biped uh with a straight hip and a straight knee. All the weight is transferred down to our knee. So, our pelvis uh has gone from an ape-like pattern where the blades were sitting on the back of the animal uh to being short and curved low and curved around the sides of the body. Now that's the pelvis. There are other changes um below the pelvis. For instance, in in the femur, our femora are longer. Uh our thigh bones are longer and they're angled inward. Uh and the knees at the knee uh we rest all our weight down from our pelvis to our knee down to our foot because we're we stand upright. In chimpanzees, their pelvis are not angled inward. They're kind of straight. Uh, and what happens is that they h they when they when their knees are when they put weight down on their knee, their knees are bent. They're angled. Uh, so their shin bones are are at an angle to the actual um femur. And that means that they're not put putting all the weight down directly on the top of their tibia like humans would. And that's because their mass is far farther forward. It's it's about the level of where the thoracic vertebrae would be um as opposed to like us where it's right over our pelvis if that makes sense.

>> One of the things that that people often talk about in the context of bipidality and what it unlocked for us or how it makes us different than other mammals that that are out there is, you know, most large-bodied mammals that run on four legs can outrun us for a while,

>> but we're really good at endurance and distance. What is sort of the story here in the thinking around things like persistence hunting, long-distance travel and and the benefits and disadvantages that bipidality had versus quadripedal locomotion.

>> Yeah. So, a colleague in my department uh Dan Lieberman is uh studied this at at length um uh spent many years studying persistent hunting and the evolution of endurance running. Uh and um the arguments there is that humans are uh dramatic really terrific long-distance runners. um we can outrun for longer distances most animals. Um it doesn't mean we we we' still be, you know, tracked down in if they were trying to catch us, they would probably track us down and eat us. But if we had a good advantage to them, we can outrun them for a very for a long time because animals often um can can run quite well, but they overheat. And one of the reasons why they overheat is because they pant. Uh whereas humans sweat. And sweating allowed us to actually run and lose heat through our bodies naturally as opposed to panting. Uh which like your dog would pant. You know, other animals would pant. Uh and so we became a very efficient runners not just from our skeletal proportions uh but also from other physiological adaptations that allowed us to run and not overheat in the process. Uh I hope that answers the question.

>> Yeah. Yeah. And so when we start to now think about the mechanics of the evolutionary changes that took place and how development had to be tweaked over time to construct muscles and bones in a more humanlike way that was conducive to bipodality rather than a more ape-like form that isn't conducive to bipodality. How do you start? How do you go about starting to study this? Obviously, you can look at the chimp, look at the human, look at the bones of the things in between and just notice the anatomic differences. Obviously, you can also take out the DNA sequences and put them side by side and look at the the genomic differences here. How do you fill in the in between part where you're thinking about how the genes encode proteins that then sculpt the anatomy into what it ends up looking like?

>> That's that's yeah, that's great. So um the first thing we do is contextualize any anatomical difference that we see between humans and chimps using the fossil record. And one of the things that we noted and it's been noted for a while is that the changes to the pelvis seem to be the earliest types of changes that we see in the fossil record. So I mentioned aripythecus andopycus. When you look at them, as I mentioned, they have relatively equalized limbs, but their pelvis blades seem to be short and narrow and somewhat curved around the sides of the body. So, Oropythecus, like Lucy, for instance, has a more humanlike pelvis. Uh, it doesn't have an exactly looking doesn't look exactly like humans, uh, but it has the short, broad, curved, uh, ilia. And so we can contextualize where to first look for the the differences in the body by actually like saying where in the fossil record do we expect to see the first changes and that's where where why we looked at the pelvis. So my lab's been focusing on the pelvis for quite a while. And the way we kind of put together um you know uh and and piece together what happened is by looking at development. So we work with human embryionic samples which are donated to us through very ethical channels. So I can talk more about that process later. Uh and we received human embriionic samples at stages where we've we've figured out where the human pelvis is actually forming. Uh and so what happens in human pelvic development is the ilia those the upper part of the pelvis I talked about already uh starts off looking more ancestral. It starts off as a thin blade that looks like it's positioned on the back of the animal. It's a thin blade, but it's made of cartilage. And let me let me pause for a second and and just describe a little bit of bone development. So almost all the bones in our body below our head form through a process called endocchondrial oification. Endo means within condr means cartilage. So it forms within a cartilage model. So what that means is that all the bones below our head basically first start off as a cartilage model. a bunch of cartilage cells called condraittes that form a model and the model looks a little bit sometimes very much like the adult bone uh and then that model gets replaced by bone cells that come in uh and start to replace the um the model from within.

>> It's almost like a mold.

>> It's like a mold. Uh it's it's like um if I looked at if you look at the development of the femur for instance in humans at some point you'll see a femur that will have the traits of a femur but they'll all be cartilage all be made of condraittes or cartilage cells and in the midshaft of the femur like the midpoint of your thigh bone uh in in a developing embryo you'll get the invasion of blood vessels that will come into the mid midshaft and bring in bone producing cells that will then replace the bone. um from the midshaft moving towards both ends uh to the head of the femur and the and towards the knee. The head of the femur would be where like your hip is and and the knee is obviously towards your knee. Uh and so the bone cells are replacing the cart. So let's go back to the pelvis. So in humans the earliest rudiment that forms this this early model is made of cartilage and it's positioned uh in the uh in the coronal plane and but it's small uh and it's not really welldeveloped. It has

>> So you're saying you're saying very early in development in humans this anatomy looks kind of apeike at first.

>> It looks apeike. It actually looks like all the primates that we looked at. So in this study, we didn't just look at like apes and and and and chimpanzees like u gorillas, chimpanzees. We looked at gibbons. We looked at all the different primates across the order. We looked at 30 different representatives across the order primates, which is a very very expansive order dating back uh you know 60 to 80 million years of evolutionary history, right? Um so so we looked at embryionic samples across those different primates that we got from museum collections. I can talk about that in a moment. But what we did was we looked at the cartilage model that was forming across the illium. And all the non-human primates started the same way. They had an illium that was cartilage and it was tall and narrow and but the cells at that stage were generally undifferiated. They didn't they didn't have specialized functions. They were just cartilage cells. At some point what happens is that those cells start to form what they call growth plates on either side of the ends of the of the model. So the in this case the upper part and the lower part of the illium just like your femur would. And those growth plates are cartilage dividing cells that make the cartilage model get bigger and bigger in the long way in the longitudinal axis in the long axis. So the ilia of of of of non-human primates all form as these kind of rods right that are vertically oriented in position in the back and humans start that way. But what happens very shortly after the model forms is it flips and you get growth occurring now not longitudinally but in the transverse direction in the perpendicular direction. So uh side to side as opposed to up and down. So whereas chimpman's and all the other primates are growing and big getting bigger and bigger and bigger ilia taller and taller ilia humans are now growing sideways they're growing perpendicular and that was a major some a major finding that we saw and never been reported before that the cart cartilage ilia changes its direction of growth in human in humans as opposed to all the other primates

>> and and that kind of helps us understand why the ilium is short and broad um as opposed to tall and narrow,

>> right? And I guess in theory, so a it didn't need to be the case that the anatomy of the earliest thing that looked like a pelvis in the embryo of apes looked the same and then they became different later. It could have been that they were just sort of built different from the ground up at the very beginning. That's not the case. So they have kind of a similar starting point and then they sort of become different later when you compare humans to other apes. And essentially what you're saying is um in in our lineage things kind of grow out rather than up you might say and that could simply be a matter of a change in a gene that pushes some type of cell one direction versus the other. That is that kind of how you start to then think about where to go next. So once we contextualize what was happening developmentally

To the to the to the structure of the illium, and we can also see through hisystology, the tissue-level biology that that's what was happening.

Then we needed to understand, well, how does that process happen? Why, where, what's causing that to actually, what's causing the pelvis to start changing its direction of growth? Uh, and that's where the genes come in and the regulatory sequences.

So, genes are, you know, segments of DNA that code for a protein. And genes are used, um, throughout the body. There's about 20,000 genes in the human genome. Uh, and you can think about there's thousands of different cell types. And each cell type expresses hundreds to thousands of different genes. So, a lot of the genes are used over and over again in different cell types in the body. But what turns a gene on is called a regulatory switch.

>> Mhm.

>> Kind of like a light switch. And this is the analogy, an analogy I give. Imagine the gene being in the light bulb, and it's like a 60-watt GE light bulb that you go to the store, Home Depot, and you buy a whole bunch of them. And every room in the house, you put that 60-watt. You need to use the light bulb in every cell. But how much of them do you need? When do you need to turn them on? All these things.

>> Exactly.

And so that light bulb and that switch, um, that light bulb is, um, is is is just that one gene, right? And then you have like, for instance, the the bathroom switch, or the kitchen switch, or the living room switch. These are independent switches that turn the light bulb on only in that room.

>> So, what we know is that genes are shared across different tissues. But regulatory switches are are present, and they're not shared. Often, they become very specific. So, in other words, when we're studying cartilage cells, we can find switches that are unique to cartilage cells and unique to the illium, and maybe not other bones in the body.

>> Right.

So, the idea here is you've got a kind of modularity and flexibility in these switches that you don't have in, uh, the bulb or the power grid. Like, if I go, if I go start messing with the power grid outside, I could accidentally turn off everyone's electricity, which is catastrophic. But if I just want to tweak the light in the bathroom, I can just mess with that one switch.

>> Exactly.

So, if you went and bought a, a defective batch of light bulbs, every light bulb would be defective, and you wouldn't have any light in your house.

>> But, you know, if it, if the light bulbs were fine, and you just had a short circuit in your switch, then only that room would lose light, right?

And, and that's really like what's happening evolutionarily is that mutations, DNA changes in the switch, because switches are DNA mutation sequences. Mutations in the switch can be tolerated if they are affecting very specific parts of the body and not the whole body at once. And so, those changes could then be beneficial if they generate a morphology, a shape, that was actually beneficial.

>> Yeah.

And let's, let's, let's bring two things into the equation here, because hopefully this will make a lot of sense to a lot of people. So, what we're really talking about here is there's a distinction to be made between protein-coding sequences in the genome and non-protein-coding sequences. So, let's talk about that and talk about how much of the genome is protein-coding versus non-protein-coding.

>> That's great.

So, uh, in the human genome, and this is true pretty much across mammals and other vertebrates, uh, about 2% of the genome is is protein-coding, uh, regions, right? Genes are not that common. They're small segments of DNA, AC, in a vast, uh, sea of DNA. Uh, most of the genome is non-coding.

>> About 98% of it is non-coding.

>> It could be a little more or less, but generally, it's around that number.

>> Vast majority is non-coding.

>> Vast majority. Yeah.

And for a long time, people just thought it was junk. And you, and you know, um, you maybe covered this before. The junk DNA is, um, a misnomer. It's not really junk DNA. It's actually made up of a lot of the rest of the DNA. 98% of it is made up of a bunch of switches. And it's made of other things too, that might not regulate gene gene regulation or how genes are turned on and off, how protein-coding genes function. Uh, but these switches are littered, scattered throughout the genome, and they're nearby genes, um, roughly, sometimes they can be pretty distant, but they're generally near genes, and they help turn on those genes in very site-specific and temporal-specific ways.

So, development, uh, of an embryo, which starts as a single cell and becomes a multicellular organism, is really how the the the non-coding sequences, the the rest of the genome, is used to turn on a small portion of genes in individual cells to orchestrate their functions and develop over time.

Mhm.

So, so, in the abstract, at least, you can start on, once you sort of understand the mechanics and the dynamics of how all that gene regulation stuff works at a detailed level, and you understand the, um, differences in the patterning of the tissue in development, like what you guys looked at, you can start to think, like, okay, um, you know, the human, the human tissues moving out in this direction, the ape tissues moving up in this direction. Maybe that was just due to a change in some of these switches that changed, sort of, when or how much growth of a particular tissue happened at some time in development.

>> Exactly.

So, when we, when we discovered that the the the growth was changing direction, uh, then we can start studying those cells and we can ask, in those cells, where are the switches? And we identified the switches in those cells and and the genes that they target, um, the, you know, the genes that they turn on and off. And, um, then we can start looking at those switches and say, hey, are these, is the sequence of these switches different between humans and other primates? Uh, and based on the the difference in sequences, we can determine whether or not these regions are likely, um, showing evidence of past evolutionary selection, um, or and therefore under some kind of adaptive evolution, or, uh, they're just changing at the natural mutation rate. And so they're not really that important for generating the or driving the phenotypes that we're interested in.

>> And so, so, yeah, after you.

So, yeah. So, so, basically, like, for a study like this, we're referring to a study that just came out. Basically, you have to understand the anatomical differences in the adult, how did, how did the pelvis and the bones and the anatomy of a human, how do they end up differently than a chimp, and compared to archaic species of hominids that aren't around anymore? And then you have to, like, line up the embryos, literally, and you look at, like, the early stages of pelvis development, and you can say, okay, all of the apes kind of look similar, but then they become different. And then you can dig into the tissue differences and how they're moving differently once they start to develop differently at these stages of development. And then you can look at the DNA of these creatures and start to really say, okay, what was driving that? And what are the genomic differences that evolved to create that tissue difference in development that gives you the the final end product having a different anatomy? So, you're really cutting across, like, multiple, what you would call, multiple fields of study here.

>> Exactly.

In the very beginning of this conversation, we talked about how we bring in data from a lot of different fields. Exactly. That's what we had to do. We're trying to connect the genotype, the genetic sequence, to the phenotype, the physical appearance of traits, and we're bringing in all these levels of inquiry, uh, to do it.

Um, and so, so when we discovered these switches, we, we then had to say, well, do they, do they, um, have harbor sequences that look like they're evolved relative to other primates?

>> Uh, and, and that's not always easy to do either.

And, you know, there's a notion out there in the field that that existed for a while, that one's going to find the gene that makes big brains, or the gene that gave a human culture, or the gene that gave language to humans, or the gene that made us upright. And the reality is that, well, first, as I mentioned, it's not the genes, it's the non-coding sequences, the other stuff. But it's not one region of the genome. And that was something that we discovered. We discovered that when we found these sequences, these switches that control the cartilage, uh, and we found evolutionary signals in those sequences, it wasn't one switch. It was hundreds of switches. Hundreds of switches targeting lots of genes across the body, across the, um, across the sk, the developing illium, uh, developing pelvis. And, and that tells us that it's a bunch of changes, of small changes, of small effect, rather than one gene of large effect, that can generate the the biological, um, phenotype that we look at.

And I think that makes a lot of sense from the standpoint that you're evolving a structure that's so critical to walking. Uh, but remember also, the pelvis is also important for giving birth to a a fetus, right? There's a birth canal that's formed by the pelvis. And so, it's not like you can just change one thing very drastically without ramifications of other other traits, like giving birth, which is huge from a dianian perspective, right? And so, the the fact that we found a whole bunch of changes, hundreds of changes, of small effect, um, really suggests that this is a gradual process, right?

>> Slowly changing the growth and trajectory of the developing illium to make it short and broad.

Why is that important? It helps us inform on the fossil record to say, you know, what do we expect now when we look at the fossil record? Do we expect to find, um, a form all of a sudden appearing out of thin air that has flipped flipped growth and a normal pelvis that looks like humans automatically? Or do we expect to find transitional fossils where the pelvic blades might have been rotated slowly and slowly over time? And the model that we have now is that the polygenicity, the many, the many different inputs that we're seeing genetically, likely reflect a a more gradual rotational process. Now, it doesn't mean this gradual process didn't happen quickly. It could happen very quickly, because it's evolutionarily speaking, if it's something selectively advantageous.

>> It could have been a 100,000-year process, which is relatively quickly. But it's, it's not like one day an ape gave birth to something that had this new kind of pelvis.

>> Yeah.

Just think about that. Like, and I've gotten people who have said, "Well, maybe it is one change." I'm like, "Well, think about it. You're that ape born with a different pelvis. How are you going to mate? How are you going to interact with other animals that have different morphology than you? You likely would not survive." And so, it's gradual shifts in the in the morphology that could happen over a 100,000-year period, or a 500,000-year period, whatever the time frame is, but it's a lot of changes that are happening, uh, across the genome. And that's the other thing is that all these, all these genes and all these switches and in in the cells that we're talking about, the chondrocytes, they're acting in networks that interact with each other. They, they, one gene's, um, when when one gene gets turned on more because the switch is activated higher, it could also mean that another gene has to be down-turned down, uh, or interacts in a different way. So, these are interactive networks, and you can't just like take a sledgehammer to the network without disrupting it. You'd make subtle changes over time, and that's what we're seeing.

>> Right.

Yeah. I mean, yeah, you brought up a lot of important points there. For those unacquainted with this realm of biology, evolution, development, and all this stuff, sometimes it's easy to overlook that, like, when we say the word pelvis, that's a word that corresponds to a concept that we made up. And like, obviously, there's a pelvis, there's like an anatomy there that we can point to, but there's no pelvis gene that does all the pelvis stuff. There's hundreds of cell types and multiple tissues that are all working together and integrated in some fashion that correspond to the pelvis. And what you're saying empirically is you didn't find differences in one or two or even three genes between all of these different apes. You found many different changes in many different genes, all of which are relevant to all of the tissues in that region of the body.

>> Yeah.

And I've been talking about the cartilage cells, but in, and but really, really what we found, uh, in the paper is, uh, is that when you look at other cell types, like muscles and tendons, uh, and even bone proper, you can start seeing lots of evolutionary changes. And, uh, it kind of makes sense because what we also discovered in this paper is that the cartilage model that forms and starts to grow in a different direction is already being anchored or attached by muscles. Uh, and that's something that's not always common, actually. Uh, the the key muscles that make us walk show connections to the cartilage model. And, and this is something surprising because the other muscles that are involved in human-specific walking do not show connections to the muscles yet, to the to the cartilage. And when we look at the muscle cells themselves and how they're anchoring to the cartilage, they also, the regulatory regions in those muscle cells also show evidence of evolutionary change, as do the tendons, uh, as do the bone cells. It's an entirely adaptive complex that's changing in a very, very complicated way over evolutionary time. And we see this across the genome and different cell types in different regulatory regions controlling those cell types. It's pretty fascinating.

>> Yeah. Yeah.

But basically, if you look at the pelvis of an ape and an archaic human and a human today, they have a different anatomy. That anatomy either facilitates or does not facilitate efficient bipedal locomotion. And some kind of model seems to be supported whereby a bunch of changes to a bunch of genes over time gradually sort of tilted and shifted how those bones and how those tissues get shaped into the geometry of the human pelvis. And that that happened over time. And, and, you know, it just, you can imagine just a pelvis going from more upright to more sideways, you know, changing the angle of the bones and all that stuff, that just sort of general shift happened in development over time after many, many different changes to many genes took root.

>> Yep.

And this is happening at a time where, um, you know, evolutionarily time, where the animal that was, where this was happening, uh, really had some other changes in their bodies compared to chimpanzees and gorillas, but nothing major. Like, they, they had about the same brain size. So,

>> Um, pressure on childbirth probably wouldn't have been there by changing.

>> This is great because I was actually going to ask you about this. I wanted to talk about, you know, co-evolution in another way. And another way that I think our pelvis is different is, you know, women have to give birth to little babies with giant heads compared to other creatures. So, it sounds like it sounds like bipedality came before most of the increase in skull size in our lineage.

>> Yeah.

So, as I mentioned, you asked the question before about what distinguishes from Homo. And really, when you get into the genus Homo, around 2.5 million years ago, you get slightly bigger brains. You, you go from 300, 400 cubic centimeters to 5, 600, 700, 800 cubic centimeters. You get to a fossil species called Homo erectus, around 1.8 million years ago, 1.6 million years ago, which is found in Africa, but now also parts of, like, East Asia. And these, these, these hominins had brain sizes of of around 800 to 1,000 cubic centimeters. But then around one, one million years ago, 1.5 million years ago, pushing back a little bit, um, brain size starts to accelerate. You start to go up to 1,500 to even 2,000 cubic centimeters, right? So, it's really within the last million, million and a half years that brain size is increasing. And it's increasing at a time where, prior to body proportions are established. Um, the our length of our legs are about what they, you know, at 1.5 million years ago are about what they are now. Um, they're long legs. We have a big toe that's brought into line, right? Our pelvis looks parasagally aligned. It looks curved around the body in a right way. And, and then you can start seeing the increase in brain size. H.

So, so, so at some point in the past, a couple, three, four million years ago, there were human-like or proto-human creatures walking around on two legs that looked like humans in the sense that they were bipedal, but they basically had chimp skulls or very small heads compared to us.

>> Yeah.

And they probably had the ability, they probably had hair, for all we know. Um, the care, like, we don't really know what they looked like, but like, they, they probably have the ability to still climb in some respects. And, and, and, and they didn't have very, uh, powerful forearms yet for throwing, right? We talked about throwing as a potential phenotype that occurs, um, more gradually. We think around, um, around 2.5 to 2 million years ago to 1.5 million years ago, with Homo erectus, you start seeing specialization of shoulders that allow throwing and projectile.

>> I see.

So, so, yeah, if we rewind the clock and then play it forward, there were creatures walking around on two legs. And then sometime later, did their heads grow? And that was probably also connected with other musculoskeletal changes, like dexterity of the hands and the ability to, you know, use your upper limbs, your arms to do things like throw spears. So, so when Australopithecus started walking on two legs, they probably, they weren't strong enough and they weren't smart enough to start hunting mammoths with spears, let's say.

>> That's the, that's the argument people make.

And it's really hard. We don't, you know, they could have been using wood tools, for all we have. No. Um, you know, one of the fascinating things that we, we, we discovered, and is that when when the pelvis shifts in its growth and starts to grow gross to the side, it inherently makes the birth canal, the upper part of the birth canal, wider. And this is at a time when the brains are still small.

>> Interesting.

So, so, it's, it's there's no way to do that without widening the birth canal. So, if I'm going to anticipate where you're going, maybe because this is just clicking in my head, the evolution of bipedality could have opened up, essentially, the niche for big skulls to actually evolve. It wasn't possible before.

>> Yeah.

That's, that's the thing I would go out on a limb, you know, and say that, you know, when humans started walking, we shifted our pelvis. One of the things that happened to our birth canal, uh, is that, well, we'll back up. In chimpanzees, the birth canal is deep from front to back, from the front of the animal to the back. Um, you know, and, and, and so it's a deep, um, more ovular structure from front to back. In humans, uh, it's wide. It's wider than deep, uh, from side to side. And when the early, when you look at, um, the birth canal of early Australopithecus and early Homo, it also is like wide and not and not deep like a chimpanzee. It's wide. And so, when the pelvis started to shift in its growth, it creates that widening. Now, the upper part of the pelvis, which is the part that the fetus coming down would first experience, is the widest. And still in modern humans, it's narrow towards the towards the bottom part where the fetus eventually comes out of. That's the pelvic outlet, and the pelvic inlet is the top part. The pelvic inlet is the widest part, and the pelvic outlet is still narrow. So, there's still a constraint. There's still a pressure to get a a big fetal head through a narrow pelvis at the bottom. But in theory, opening up of a larger, um, up pelvic inlet, the upper part, could have allowed for brain sizes to be accommodated during fetal growth. And then, of course, humans do things like rotate the fetus during birth to maybe shift them and position them correctly. And, and our, our hypothesis moving forward, and we're trying to study this in the lab now, is potentially, um, is really that the earliest changes to to the pelvis facilitated, as you said, um, the the ability to allow variation to develop in in in brain size later on, and that was tolerated, and that could actually be passed through the fe through the birth canal. It's a pretty fascinating contingency, right?

>> Yeah. Yeah.

Interesting. It also sort of explains why, you know, people might ask the seemingly simple question like, well, why aren't there why aren't there more types of really smart creatures? And one answer is, you know, for a mammal, you have to give birth to the babies through the birth canal. And if it's not already wide enough to accommodate a bigger brain, then you, you can't get that, because then the baby can't, you can't give birth to it.

>> Yeah.

It's pretty, it's pretty amazing. Um, you know, I, I think of evolution as a bunch of contingencies. Uh, things that has that happened before that affect later. They're constraints, and, and this is potentially one of them. Uh, it might have actually not been a constraint as much as something that facilitated future, future, um, brain growth, though.

>> Mhm.

Now, now, in that line, if I, if I may, like, one of the other things that we discovered in the paper on the pelvis that we recently, we published, is that when the pelvis, pelvic ilia rotate and start to grow to the sides, they also change their type of bone formation. So, all the long bones of the body, like your femur, uh, even the ilia of other primates and ilia of mouse, the mouse model, they all, when you get bo, um, blood vessels coming in into the middle part of the of the element, uh, the skeletal element, you, you actually get bone cells coming in, and those bone cells start to mineralize internally and get hard bone internal and ex and externally. Uh, so when you look at chimpanzees, that seems to be the process. Those ilia that are forming along the mid part of the ilia, you get internal ossification and external ossification, bone, bone mineralization internally and externally. In humans, what we found remarkably is that the ilia that are growing, they get blood vessels to come in, but they don't bring bone cells internally. There's actually a block to the bone cells entering into the actual developing ilia, iliac model. They stay on the peripheral side, the external. They coat the model. They don't internalize. And what that means is that humans have delayed the internal ossification of the developing illium. Now, now, why would that be important? Well, inside the ilia are still cartilage cells that can divide and grow. So, if you create a shape, and then you need to grow that shape as the fetus grows, you can grow that fe, that that that the pelvis wider, bigger, and bigger, and bigger, and still maintain the proportions. And if those proportions are important for walking, but also now a large fetal head in the future, when that individual has to give birth, right? Uh, then you want those proportions to maintain. So, what you do is you delay the bone development internally, and you just coat it on the external surface, allowing the cells to, internal cells to divide and divide, divide, because they're cartilage. Now, I went into that pretty ri, pretty, pretty quick, but like, the idea is that there's another adaptation that we identified that might link to to brain evolution.

>> Yeah.

And I wanted to ask you about brain evolution to some extent, and muscle evolution. So, earlier you mentioned, you know, you know, everything's about trade-offs. Energetic trade-offs. There's only so much energy that an organism ever has, and you've got to allocate it and pattern it in some way. And it's finite, right? So, the more you put into reproductive output, the less you can put into growing a bigger brain. The more that you put into muscles, the less leftover for other tissues. And so, everything's about these constraints and these trade-offs in terms of how energy is used to build and build tissue, build phenotypes, and, and then, you know, deploy it one way or the other. One of the areas that I know that there's been a lot of thinking around in terms of, you know, the human story is, okay, we started walking upright, and that had certain energetic advantages that we touched on earlier. We can go over distances. Um, it opened up our ability to eventually, you know, use our hands and do tool-making stuff like that. But, you know, we've also got these big brains that we, you know, we just touched on like the some of the anatomical constraints there that may have paved the way or enabled us to evolve these big brains. But when we did start building really big brains, doing, um, fancier, fancier human-type stuff, that has to come with a trade-off, right? And one of the potential trade-offs here is sort of brain versus muscle versus maybe other tissues we can talk about. Maybe one way to hook into this is people are always struck when they see the the hairless chimpanzee, right? Chimpanzees are just, they're jacked. Like, you could take the toughest human MMA fighter and the the most average chimp, and the chimp would just rip their arm off. What can you start to tell us about some of the trade-offs between say, muscle, just total musculature, and like how our muscles are different and have changed, and how that might relate to things like, you know, building the bigger brain over time?

>> That's a great, great question.

So, um, I'm working with a collaborator at the University of Oregon, uh, Kirsten Sterner, on this, looking at the evolution of muscle fiber types. So, there are there are fibers in muscle, and they can be power muscles involved in power generation. They can also be muscles involved in endurance biology. Um, and so, they're, they're different energetic costs to each.

>> These are the type one, type two fibers that we?

>> Type two fibers. Yeah.

>> Which one's which? I always forget.

The the type one fibers are the fast twitch, and the type, type two fibers are fast twitch. Type one and the slow twitch. Um, so generally, what you see is, um, the evolution in humans, as of having more slow-twitch fibers. Okay. So, there's been an evolutionary process by which, um, human muscles have actually acquired slow-twitch muscles and fiber types. And, um, previous work showed that actually, when you look at most muscles in the body, there's actually lots of more slow-twitch muscles in fibers in humans compared to chimpanzees. So, some people have argued that in the hind limb, used in walking, that the muscles like the gastro, the the calf muscle, which is a slow-twitch dominated muscle, would would have evolved because you need that muscle to walk in, in, in terms of endurance walking and and running. Uh, and that by having slow-twitch fibers, what you're doing is you're allowing them to recover, the muscle to recover more quickly, uh, and for longer periods of time. So, um, and unlike power muscles, which, you know, you use, you use a lot of energy, energy for, but the recovery time is slower, and that's really the kind of the difference between the two. And so, um, when you look at the hind limb, yes, you see differences in slow-twitch contributions in humans compared to chimpanzees, but you also see that across the body. And it does make one to suggest that potentially there had to be some type of energetic cost, uh, to to having large brains, that potentially as we got, we we acquired larger brains, we had to shift our energetic costs in other ways, potentially by generating slow-twitch fibers across our muscles. Uh, and that's, but that's really hard to say because we started to evolve endurance locomotion, uh, at the time when our brains are are are evolving and getting bigger, right? Uh, and so, you know, it maybe not a trade-off. It actually might have been two adaptations.

Um, another way one can think about it is looking at the relative energetic use of different organs in the body. And so, the brain uses lots of energy. Uh, but other organs in the body use less. Uh, and it's been argued in human evolution that the human brain uses more energy than the chimp brain, uh, relative to body size. Uh, and that even, um, and that our guts have actually become more efficient and smaller, uh, as opposed to other primates, right? Have larger sacculated guts for processing leaves and stuff. And so, people can now look at different organs in their energetic uses to really look at these trade-offs in more detail, rather than just looking at the muscles and thinking about the relationship of muscle changes to brain changes, we can look at all the whole organism and all the different organs to know where are the trade-offs happening, right? If that makes sense.

>> Yeah. Yeah. Yeah.

And so, is it just that we have proportionally more of these slow-twitch endurance type fibers, or how, how is our, like, just total muscle mass change? It certainly looks like a chimpanzee is just more muscular overall.

>> Yeah. Human human muscles are generally smaller, you know, than than than chimpanzees and gorillas, right? Of course. Uh, and they are made up of predominantly more muscles, more, um, um, slow-twitch muscle fibers. So,

>> More slow-twitch ones? Slow-twitch. Humans are made up of more so?

>> Humans are slow-twitch. Yeah.

>> Oh, they're they're smaller muscles, um, per body size, and they're also, um, generally, um, red, um, reduced fast-twitch or increased slow-twitch, um, contribution.

After you.

Um, no, I was going to say, I don't know if this is your area that you've studied in particular, but when we think about these changes to the musculoskeletal system generally, when we think about bipedality and then the origins of bigger brains, the other thing I wanted to ask you about is our other two limbs. When do we start to see some of those shoulder, arm changes that facilitate things like hunting with tools and doing that sort of thing?

>> Yeah, it's this is a very, very interesting question.

Um, so, when we had worked on this project, I worked on the project a while back in 2015 with, uh, Nathan Young and Neil Ro, who, who basically, we're looking at the the pectoral girdle and the shoulder girdle. And what we, what we argued there in that paper, um, was basically that over the course of human evolution, and unlike what you see in the pelvis, the changes to the shoulder were more gradual. In, let me put this in perspective. In in chimpanzees, in gorillas, and gibbons, for instance, the should, the scapula, or shoulder blade, the thing that sits on your back, right? That you can feel if you touch on your out your back. The this shoulder is oriented in such a way that the the joint, the shoulder joint, is in, in those chim, in those primates, faces more, um, towards the, not directly in line with the vertebral column, but like on an angle to them. So, basically, they're, um, they're, they're basically pointed more cranially. That's the way you describe it. In humans, our shoulder joints face laterally. If you ever seen an X-ray of a human, you'll know that the scapula and the the the the humerus head, or the humerus, comes right off the scapula on the sides of the body, laterally. And, and so when, when we modeled evolutionarily what was happening in fossil hominins, we can see that there was a gradual rotation from that cranial orientation to the lateral rotation. And the lateral rotation, the true human pattern, is found at about Homo erectus. So, that would be the period where one would argue that potentially high-powered spear throwing and potentially tool use was most, um, was most, um, adaptive at that point.

>> I see. The pelvic changes you mapped out that facilitated the evolution of bipedality, those didn't come overnight, but you're saying all of these upper body changes were even more gradual?

>> It seems.

>> More gradual. Yeah.

They they definitely took place over several millions of years. Uh, fossil hominins that you, if you, if you can place them along a trajectory as being either more cranially, if they're earlier in time, or more laterally, if they're later in time. Whereas in the pelvis, we don't have a lot of fossils from that early, early window of 4.5 to six to six or eight million years ago, but it looks like that would have been a more drastically faster process, right?

Um, and, and, you know, this is, this is an interesting question to me is, um, you know, if, if scapula are, or shoulder blades are are becoming more lateralized over time,

>> Um, that's kind of what's also happening in the pelvis, but, uh, in a different, in a different, in in the pelvic.

It seems to be through the mechanism of shifting the growth.

>> Yeah.

We're now in my lab, we're trying to understand what's happening in the shoulder to see if it's actually shifting its growth as well.

>> Right.

It could be a similar morphogenetic move that evolution made, just with different switches or something.

>> Exactly.

It could be that ingrained in the genetic architecture of building the pelvis is a bunch of switches and genes that are in a network that could have been co-opted again or used again to shape the the scapula, or maybe the scapular morphology is is more ancestral to the, um, to to the pelvic morphology, and that's a much more involved question. But in any case, like, the idea is generally that could evolution instead of evolution recreating the wheel,

>> It just uses the wheel already. It uses the wheel again to actually generate this a new morphology.

>> That's fascinating.

What, um, what other questions and problems are you working on in the lab today related to human evolution?

>> Oh, great.

So, so, as I mentioned, we're, we're looking at the pelvis, but now we're studying the birth canal. So, we're trying to understand how is the human birth canal forming? It's remarkable that we know very little about this really critical structure. And so, we're looking at the shape of the other parts of the pelvis, which is the, uh, uh, ischium and pubis. The pubis is the interior part of the pelvis that you see on an X-ray. The, uh, and we're looking at how that birth canal forms.

We're studying the shoulder, as I mentioned. We're also, uh, studying the lower back. So, the lumbar vertebrae and how they connect to the sacral vertebrae. The pelvis itself is the, the ilia connected to the sacrum, or the sacral vertebrae. And over the course of human evolution, humans have developed a lordotic curve, or S-shaped curve, in their vertebrae to push the center of mass over over their pelvis.

We're trying to understand that as well developmentally. Uh, chimpanzees have more of a, a C-shaped vertebrae, whereas humans have an S-shaped, um, lower, lower lumbar region. And we're trying to understand that mechanism as well. And that might be tied to how the pelvis is forming also. It's a whole adaptive complex.

Um, we have projects on the knee and how the knees have evolved. Uh, we have projects on the hands and feet. We have a paper that we've just submitted, uh, uh, looking at the molecular architecture of how hands and foot, feet develop, and how their proportions develop in humans. Um, shoulders. We're looking at the shoulders. And, um, recently, I have a student who said she came into my lab and said, "I want to study the brain." And I'm not a brain lab, you know, but I said, "Let's do it. Let's try to use the tools that we have to study the brain." And what we're trying to do is study these cells called the microglia, which are supporting cells to neurons in the brain. And there's some evidence in human evolution that microglia have changed functions, uh, as support cells. It's potentially equally important that they've changed, in addition to neurons, in the in the in the in the brain to support human brain development and diversification. So, we're that project as well.

Is is there anything that you want to reiterate for people, or any final thoughts you want to leave them with, particularly as it relates to, you know, how to think about things in an evolutionary context, and sort of all the things you need to keep in mind to, um, to think to think well, and not just sort of make up just-so stories when it comes to this stuff?

Yeah, it's something I, I mentioned in the very beginning that I, I truly, uh, hold dear. Uh, when you develop a hypothesis or a model, you, the model has to be supported. The assertions you're making have to be supported by the data. And the data, and all types of data. And if there's a type of data that doesn't support your model, uh, first question whether the data are are good, they're generated in a robust way. And if they were, you can't ignore them. You can't, you know, ignore that one class of data because it doesn't make sense. In our studies on the developing pelvis, we incorporated all these different data sets, and they made sense. They connected very well. Uh, and we did not have to ignore pieces of data. In fact, we modified our model along the way as we learned more about the, um, the different contributions from different data types. And so, we want our hypotheses to be robust and strong. And they have to be strong against all different types of of inquiry, right? And that's what I think is probably most important.

Um, the other thing I would say is from an evolutionary lens, that there's, um, that the tissues and biology is complex. It's hierarchically complex in very different ways, in very complicated ways, with lots of genes and regulatory sequences and networks interacting with themselves. And, um, there's likely no gene for for a trait. It's more a complicated series of changes that have to be tolerated and allow for, allow for the generation of variation in a trait for the selection to occur to that trait to eventually manifest into what we see in nature. And that's going to be under, that's going to be underpinned by many different genetic changes, uh, not just one.

All right. Well, Professor Terrence Kapalenni, thank you very much for your time. This was fascinating.

>> Oh, thank you. It was a wonderful conversation. I appreciate it.

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