Information

29.7B: Early Human Evolution - Biology


Modern humans and chimpanzees evolved from a common hominoid ancestor that diverged approximately 6 million years ago.

Learning Objectives

  • List the evolved physical traits used to differentiate hominins from other hominoids

Key Points

  • Modern humans are classified as hominins, which also includes extinct bipedal human relatives, such as Australopithecus africanus, Homo habilis , and Homo erectus.
  • Few very early (prior to 4 million years ago) hominin fossils have been found so determining the lines of hominin descent is extremely difficult.
  • Within the last 20 years, three new genera of hominoids were discovered: Sahelanthropus tchadensis, Orrorin tugenensis, and Ardipithecus ramidus and kadabba, but their status in regards to human ancestry is somewhat uncertain.

Key Terms

  • hominin: the evolutionary group that includes modern humans and now-extinct bipedal relatives
  • hominoid: any great ape (such as humans) belonging to the superfamily Hominoidea

Human Evolution

The family Hominidae of order Primates includes chimpanzees and humans. Evidence from the fossil record and from a comparison of human and chimpanzee DNA suggests that humans and chimpanzees diverged from a common hominoid ancestor approximately 6 million years ago. Several species evolved from the evolutionary branch that includes humans, although our species is the only surviving member. The term hominin (or hominid) is used to refer to those species that evolved after this split of the primate line, thereby designating species that are more closely related to humans than to chimpanzees. Hominins, who were bipedal in comparison to the other hominoids who were primarily quadrupedal, includes those groups that probably gave rise to our species: Australopithecus africanus, Homo habilis, and Homo erectus, along with non- ancestral groups such as Australopithecus boisei. Determining the true lines of descent in hominins is difficult. In years past, when relatively few hominin fossils had been recovered, some scientists believed that considering them in order, from oldest to youngest, would demonstrate the course of evolution from early hominins to modern humans. In the past several years, however, many new fossils have been found. It is possible that there were often more than one species alive at any one time and that many of the fossils found (and species named) represent hominin species that died out and are not ancestral to modern humans. However, it is also possible that too many new species have been named.

Very Early Hominins

There have been three species of very early hominoids which have made news in the past few years. The oldest of these, Sahelanthropus tchadensis, has been dated to nearly seven million years ago. There is a single specimen of this genus, a skull that was a surface find in Chad. The fossil, informally called “Toumai,” is a mosaic of primitive and evolved characteristics. To date, it is unclear how this fossil fits with the picture given by molecular data. The line leading to modern humans and modern chimpanzees apparently bifurcated (divided into branches) about six million years ago. It is not thought at this time that this species was an ancestor of modern humans. It may not have been a hominin.

A second, younger species (around 5.7 million years ago), Orrorin tugenensis, is also a relatively-recent discovery, found in 2000. There are several specimens of Orrorin. It is not known whether Orrorin was a human ancestor, but this possibility has not been ruled out. Some features of Orrorin are more similar to those of modern humans than are the australopiths, although Orrorin is much older.

A third genus, Ardipithecus ramidus (4.4 million years ago), was discovered in the 1990s. The scientists who discovered the first fossil found that some other scientists did not believe the organism to be a biped (thus, it would not be considered a hominid). In the intervening years, several more specimens of Ardipithecus, including a new species, Ardipithecus kadabba (5.6 million years ago), demonstrated that they were bipedal. Again, the status of this genus as a human ancestor is uncertain, but, given that it was bipedal, it was a hominin.


Timeline of human evolution

The timeline of human evolution outlines the major events in the evolutionary lineage of the modern human species, Homo sapiens, throughout the history of life, beginning some 4.2 billion years ago down to recent evolution within H. sapiens during and since the Last Glacial Period.

It includes brief explanations of the various taxonomic ranks in the human lineage. The timeline reflects the mainstream views in modern taxonomy, based on the principle of phylogenetic nomenclature in cases of open questions with no clear consensus, the main competing possibilities are briefly outlined.


Lactose intolerance

Adult lactose intolerance is a global norm, not an exception or an illness. (Piqsels)

Lactose intolerance occurs when we can’t digest milk sugars (lactose) in adulthood. This can cause nausea, cramping, gas and diarrhea, and is considered a medical condition.

Lactose is broken down by the enzyme lactase. Adult production of lactase evolved in human populations that domesticated animals about 10,000 years ago. These populations were found in northern and central Europe, and in pastoral communities in Africa. Milk is a calorie- and nutrient-dense food, meaning that people who could digest lactose would be better nourished, giving them a better chance at survival and reproduction.

Mutations allowing for adult digestion of lactose gradually spread over generations within these populations. However, those with ancestors from populations that did not regularly herd and milk domesticated animals, such as Indigenous populations in North and South America and most Asian populations, do not possess this ability. In fact, roughly 65 per cent of adults worldwide remain lactose intolerant.

If 65 per cent of the global population cannot digest lactose, why is it treated as an illness? There is nothing “wrong” with someone who is lactose intolerant no intervention is needed other than to avoid or limit dairy consumption. Evolution tells us that lactose intolerance is perfectly normal. We simply need to redefine illness.


Human Evolution

Learn how early humans evolved from Homo habilis, to Homo erectus, to Homo sapiens and developed basic survival tools.

Anthropology, Archaeology, Biology, Genetics

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Related Resources

Out of Eden Walk

Paul Salopek, a National Geographic Fellow and Pulitzer Prize-winning journalist, is conducting an experiment in slow journalism by retracing the journey of some of our human ancestors&rsquo migration beyond Africa. He began his multiyear journey in 2013 in Ethiopia, and will walk around 33,800 kilometers (21,000 miles) ending at the southern tip of South America. Along the way, he is walking with guides, stopping to speak with local people and document their stories, and sharing his experiences along the way.

Evolution

In the mid-1800s, Charles Darwin famously described variation in the anatomy of finches from the Galapagos Islands. Alfred Russel Wallace noted the similarities and differences between nearby species and those separated by natural boundaries in the Amazon and Indonesia. Independently they came to the same conclusion: over generations, natural selection of inherited traits could give rise to new species. Use the resources below to teach the theory of evolution in your classroom.

Human Origins

Where did we come from? Humans continue to search for the answer to this fundamental question. Over the years, we've turned to both religion and science to explain where our species came from. Innovators of their time, Charles Darwin and Alfred Russel Wallace, used science to explain where humans came from, posing the theory of evolution. Then, Mary and Louis Leaky explored the fossil record to see if they could piece together the story of humans. Evolutionary science and archaeology continue today. Use these materials in your classroom to teach your students about the origins of the homo sapien.

Evolution: Changing Species Over Time

Evolution is the process by which species adapt over time in response to their changing environment. Use these ideas to teach about the water cycle in your classroom.

Neanderthal 101

Who were the neanderthals? Do humans really share some of their DNA? Learn facts about neanderthal man, the traits and tools of Homo neanderthalensis, and how the species fits into our evolution story.

Human Origin 101

The story of human evolution began about 7 million years ago, when the lineages that lead to Homo sapiens and chimpanzees separated. Learn about the over 20 early human species that belong in our family tree and how the natural selection of certain physical and behavioral traits defined what it means to be human.

Related Resources

Out of Eden Walk

Paul Salopek, a National Geographic Fellow and Pulitzer Prize-winning journalist, is conducting an experiment in slow journalism by retracing the journey of some of our human ancestors&rsquo migration beyond Africa. He began his multiyear journey in 2013 in Ethiopia, and will walk around 33,800 kilometers (21,000 miles) ending at the southern tip of South America. Along the way, he is walking with guides, stopping to speak with local people and document their stories, and sharing his experiences along the way.

Evolution

In the mid-1800s, Charles Darwin famously described variation in the anatomy of finches from the Galapagos Islands. Alfred Russel Wallace noted the similarities and differences between nearby species and those separated by natural boundaries in the Amazon and Indonesia. Independently they came to the same conclusion: over generations, natural selection of inherited traits could give rise to new species. Use the resources below to teach the theory of evolution in your classroom.

Human Origins

Where did we come from? Humans continue to search for the answer to this fundamental question. Over the years, we've turned to both religion and science to explain where our species came from. Innovators of their time, Charles Darwin and Alfred Russel Wallace, used science to explain where humans came from, posing the theory of evolution. Then, Mary and Louis Leaky explored the fossil record to see if they could piece together the story of humans. Evolutionary science and archaeology continue today. Use these materials in your classroom to teach your students about the origins of the homo sapien.

Evolution: Changing Species Over Time

Evolution is the process by which species adapt over time in response to their changing environment. Use these ideas to teach about the water cycle in your classroom.

Neanderthal 101

Who were the neanderthals? Do humans really share some of their DNA? Learn facts about neanderthal man, the traits and tools of Homo neanderthalensis, and how the species fits into our evolution story.

Human Origin 101

The story of human evolution began about 7 million years ago, when the lineages that lead to Homo sapiens and chimpanzees separated. Learn about the over 20 early human species that belong in our family tree and how the natural selection of certain physical and behavioral traits defined what it means to be human.


The layers that contain fossils and archeological clues can be dated by more than a dozen techniques that use the basic principles of physics, chemistry, and Earth sciences. Some techniques can even estimate the age of the ancient teeth and bones directly. Advances in dating have made human evolution very exciting!


What is the genetic evidence for human evolution?

In the last couple of decades, our understanding of genetics has grown dramatically, providing overwhelming evidence that humans share common ancestors with all life on earth. Here are some of the main types of genetic evidence for common ancestry.

1. Genetic Diversity. Human children inherit 3 billion base pairs of DNA from each parent, but they are not an exact duplicate. The rate of change has been measured precisely to an average of 70 bases (out of our 6 billion total) per generation. So as we go back on the family tree, there are more and more genetic differences between us and our ancestors. For example, there would be about 140 differences between your DNA and that of your four grandparents, and 210 differences between you and your eight great-grandparents, and so on. That enables us to make a prediction from the amount of genetic diversity between two species about the time since their common ancestor population lived. Using non-genetic evidence, the common ancestor between humans and chimpanzees was estimated to have lived about 6 million years ago. The calculation from genetic differences gives a figure remarkably close to the estimated value.

2. Genetic “scars”. Just as scars stay on our bodies as reminders of past events, the DNA code contains “scars” and these are passed on from generation to generation. DNA scars result from the deletion or insertion of a block of bases (not just single base changes as in the previous section). Because we have a lot of these (hundreds of thousands) and they can be precisely located, they serve as a historical record of species. If we have the same scar as chimpanzees and orangutans, then the deletion or insertion must have occurred before these species diverged into separate populations. If we and chimpanzees have a certain scar but orangutans do not, we can conclude the deletion or insertion must have occurred after the common ancestor of chimps and humans separated from our common ancestor with orangutans. In this way we can create a detailed family tree of common ancestors.

3. Genetic synonyms. In a certain context, the words “round” and “circular” mean the same thing to an English speaker—they are synonyms. So too, there are “synonyms” in the genetic code—different sequences of DNA bases that mean the same thing to cells (that is, they cause the production of the same proteins). Mutations in the genetic code are often harmful, resulting in an organism not being able to successfully reproduce. But if the mutation results in a “synonym”, the organism would function the same and continue passing on its genes. Because of this we would expect the synonymous changes to be passed on much more effectively than non-synonymous changes. That is exactly what we find among the DNA of humans and chimpanzees: there are many more synonymous differences between the two species than non-synonymous ones. This is exactly what we would expect if the two species had a common ancestor, and so it provides further evidence that humans and chimpanzees were created through common descent from a single ancestral species.

The more research that is done on DNA, the more evidence we find that all life is related.

Last updated on March 11, 2019

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Early Humans, Neanderthals, Denisovans Mixed It Up

After the superarchaic humans came the archaic ones: Neanderthals, Denisovans and other human groups that no longer exist.

Archaeologists have known about Neanderthals, or Homo neanderthalensis, since the 19th century, but only discovered Denisovans in 2008 (the group is so new it doesn’t have a scientific name yet). Since then, researchers have discovered Neanderthals and Denisovans not only mated with each other, they also mated with modern humans.

“When the Max Plank Institute [for Evolutionary Anthropology] began getting nuclear DNA sequenced data from Neanderthals, then it became very clear very quickly that modern humans carried some Neanderthal DNA,” says Alan R. Rogers, a professor of anthropology and biology at the University of Utah and lead author of the Science Advances paper. “That was a real turning point… It became widely accepted very quickly after that.”

As a more recently-discovered group, we have far less information on Denisovans than Neanderthals. But archaeologists have found evidence that they lived and mated with Neanderthals in Siberia for around 100,000 years. The most direct evidence of this is the recent discovery of a 13-year-old girl who lived in that cave about 90,000 years ago. DNA analysis revealed that her mother was a Neanderthal and her father was a Denisovan.


Evolution Explains Nothing

“Blurk” is a new word, just made up. Let us substitute it into sentences typically found in papers about evolution:

  • Scientists determine how the hippopotamus blurked a thick skin.
  • Blurky medicine finds reasons for human diseases like diabetes.
  • Unrelated species arrived at similar leaf shapes by convergent blurkification.
  • The new research sheds light on how the process was orchestrated by blurk to its present optimum.
  • The investigators feel their work brings us closer to understanding how life originally blurked.

Now, teach this word to students K through 12 and on into college and grad school. Tell them all scientists believe in blurk. Those minority anti-blurkers are a stain on science and an embarrassment to their country. Unless students learn how blurk works, their country will fall behind in scientific leadership. What is blurk? Whatever it means, it implies change over time, which can be up, down, or sideways (19 Dec 2007), and it comes about by the Stuff Happens Law. The goal for all science majors is to shloop their way to becoming reputable blurkists. Then they will gain “understanding.”

Is this how evolutionary explanations really look in print? Let readers be the judge.

Evolution: How to evolve a thick skin (Current Biology). “A new study examines anatomy and genetics of skin in whales and hippos and reveals that adaptations to aquatic and semi-aquatic lifestyles evolved [blurked] convergently in these lineages.” The article uses the e-word “evolution” (and its derivatives) 13 times without explaining what actually happened.

The question of whether these water-friendly adaptations of the skin were evidence of shared ancestry, the product of convergent evolution, or something in between has nagged at veteran researchers of this problem for years.

Whales and hippos have thick skin. They are similar but different. Their skin blurked at different times. Whatever happened made both animals successful in their watery habitats. It was an “evolutionary [blurky] breakthrough,” and now a detailed study “sheds light on the evolution [blurk] of whale and hippo integument,” Nina Jablonski writes. She holds it up as a model for students to learn: “This paper makes textbook reading for aspiring students of the twenty-first century comparative method,” she says. The study demonstrates that “skin is a dynamic part of the mammalian evolutionary [blurky] story and that we have only begun to unlock its fascinating secrets.” Studying how blurk works, in other words, is leading science to a nirvana of understanding.

How army ants’ iconic mass raids evolved (Phys.org). Harvard scientists have concluded that “army ant mass raiding evolved [blurked] from a different form of coordinated hunting called group raiding through the scaling effects of increasing colony size.” This is like saying that small gangs “evolved” into big gangs when their memberships increased. The ants are all just ants with the behavior of raiding in numbers. What’s evolution got to do with it?

Telling Up from Down: How Marine Flatworms Learn to Sense Gravity (Okayama University): Observation: flatworms can tell up from down because they have an organ called a statocyst that contains a piece of rock (a statolith) that is monitored by sensory proteins that send messages about movement through neurons to the brain. Flatworms gain this function shortly after hatching. It is an amazing system made up of numerous parts. It looks irreducibly complex. It’s not as fancy as the gravity sensing organ of a vertebrate, but it works well for a small, “simple” animal. What’s evolution got to do with it? Professor Montonori Aldo says you need the Theory of Blurk to gain “understanding.” Meditate on blurk until the understanding arrives.

Understanding the stimulus response mechanism of Acoela [animals without internal cavities] can uncover a fundamental biological control mechanism that dates back to the origin of bilaterian animals, including humans. These organisms, therefore, are key to unravelling the process of evolution.

Aging as a consequence of selection to reduce the environmental risk of dying (Omholt and Kirkwood, PNAS 1 June 2021). Since aging happens, there must be a blurky reason for it. The Stuff Happens Law wouldn’t do something without a good reason.

A fresh perspective on the evolution of aging is developed, which focuses on optimizing an individual’s exposure to mortality risk across the life course. A significant source of risk is associated with the act of acquiring the energy necessary for all functions of life. In particular, a considerable fraction of lifetime energy acquisition is used for somatic maintenance. We show how reduction of mortality risk through restrained allocation to somatic maintenance may enhance lifetime fitness but result in aging. Our results are discussed in relation to current theories of the evolution of aging, where we anticipate it will help to illuminate the debate about the mechanisms underlying aging in the wild and the nature and roles of trade-offs.

Did that make any sense? Who decided to select for this strategy? Evolution? Come on. Omholt and Kirkwood simply shloop their way to a process that somehow “may enhance” lifetime fitness. Maybe “stabilizing selection” led to it. Their “fresh perspective” they hope “will help to illuminate the debate” about how aging blurked. Now you understand, don’t you? This explains why parents often live for decades after their childbearing years, right? Here’s their concluding remark: “We acknowledge that further theoretical as well as experimental work will be needed before one can reach a firm conclusion on the explanatory scope of the hypothesis we propose in this paper.” OK, then, forget everything they said.

Evolutionary medicine looks to our early human ancestors for insight into conditions like diabetes (The Conversation). Three Darwin-drunk writers declare their mastery of using blurk for divination: “Like all living things, humans are the product of a complex evolutionary history.

A more profound understanding of our evolution is necessary to offer better health care to our entire community. Before medicine can move forward, we must understand where we came from.

Ah, the promised understanding. But if we come from mindless process of blurking, then blurk doesn’t care if we live or die. It takes a human being made in the image of God to care about other human beings. Why should a Doctor of Blurk care about you if they cannot pass on your genes, and don’t give a whit about your fitness.

Why do we grow more hair on our heads than on our bodies? (Live Science). Observation: humans unlike other primates are mostly naked, but have hair on their heads. There must be a blurky reason for it, and Tara Santora is here to give readers understanding with the aid of her chosen Doctor of Blurk Theory, Mark Pagel. Humans could afford to drop their hair, he says, “because they had the unique ability to compensate with fire, shelter and clothing.” Shlooping along, Pagel explains that head hair remained because it acts like a built-in hat, but keeps the brain warm at night, too. The blurking process worked all this out without thinking, you see that’s why naked mole rats and badgers, both mammals that dig in dirt, came to opposite strategies. But maybe it was sexual selection. Or perhaps the aquatic ape theory was part of it. Or maybe parasites prefer furry mammals instead of naked ones. Choose the blurk notion that best increases your understanding. All is fair except paying attention to the rascally anti-blurkers out there.

Paul spoke of people like this: proud, ignorant, and self-deceived. “Now this I say and testify in the Lord, that you must no longer walk as the Gentiles do, in the futility of their minds. They are darkened in their understanding, alienated from the life of God because of the ignorance that is in them, due to their hardness of heart” (Ephesians 4:17-18). The Psalmist noted, “Man in his pomp yet without understanding is like the beasts that perish” (Psalm 49:20). Understanding comes from knowing the Creator and having a relationship with him by faith: “Your hands have made and fashioned me give me understanding that I may learn your commandments” (Psalm 119: 73).


How Europeans evolved white skin

ST. LOUIS, MISSOURI—Most of us think of Europe as the ancestral home of white people. But a new study shows that pale skin, as well as other traits such as tallness and the ability to digest milk as adults, arrived in most of the continent relatively recently. The work, presented here last week at the 84th annual meeting of the American Association of Physical Anthropologists, offers dramatic evidence of recent evolution in Europe and shows that most modern Europeans don’t look much like those of 8000 years ago.

The origins of Europeans have come into sharp focus in the past year as researchers have sequenced the genomes of ancient populations, rather than only a few individuals. By comparing key parts of the DNA across the genomes of 83 ancient individuals from archaeological sites throughout Europe, the international team of researchers reported earlier this year that Europeans today are a mix of the blending of at least three ancient populations of hunter-gatherers and farmers who moved into Europe in separate migrations over the past 8000 years. The study revealed that a massive migration of Yamnaya herders from the steppes north of the Black Sea may have brought Indo-European languages to Europe about 4500 years ago.

Now, a new study from the same team drills down further into that remarkable data to search for genes that were under strong natural selection—including traits so favorable that they spread rapidly throughout Europe in the past 8000 years. By comparing the ancient European genomes with those of recent ones from the 1000 Genomes Project, population geneticist Iain Mathieson, a postdoc in the Harvard University lab of population geneticist David Reich, found five genes associated with changes in diet and skin pigmentation that underwent strong natural selection.

First, the scientists confirmed an earlier report that the hunter-gatherers in Europe could not digest the sugars in milk 8000 years ago, according to a poster. They also noted an interesting twist: The first farmers also couldn’t digest milk. The farmers who came from the Near East about 7800 years ago and the Yamnaya pastoralists who came from the steppes 4800 years ago lacked the version of the LCT gene that allows adults to digest sugars in milk. It wasn’t until about 4300 years ago that lactose tolerance swept through Europe.

When it comes to skin color, the team found a patchwork of evolution in different places, and three separate genes that produce light skin, telling a complex story for how European’s skin evolved to be much lighter during the past 8000 years. The modern humans who came out of Africa to originally settle Europe about 40,000 years are presumed to have had dark skin, which is advantageous in sunny latitudes. And the new data confirm that about 8500 years ago, early hunter-gatherers in Spain, Luxembourg, and Hungary also had darker skin: They lacked versions of two genes—SLC24A5 and SLC45A2—that lead to depigmentation and, therefore, pale skin in Europeans today.

But in the far north—where low light levels would favor pale skin—the team found a different picture in hunter-gatherers: Seven people from the 7700-year-old Motala archaeological site in southern Sweden had both light skin gene variants, SLC24A5 and SLC45A2. They also had a third gene, HERC2/OCA2, which causes blue eyes and may also contribute to light skin and blond hair. Thus ancient hunter-gatherers of the far north were already pale and blue-eyed, but those of central and southern Europe had darker skin.

Then, the first farmers from the Near East arrived in Europe they carried both genes for light skin. As they interbred with the indigenous hunter-gatherers, one of their light-skin genes swept through Europe, so that central and southern Europeans also began to have lighter skin. The other gene variant, SLC45A2, was at low levels until about 5800 years ago when it swept up to high frequency.

The team also tracked complex traits, such as height, which are the result of the interaction of many genes. They found that selection strongly favored several gene variants for tallness in northern and central Europeans, starting 8000 years ago, with a boost coming from the Yamnaya migration, starting 4800 years ago. The Yamnaya have the greatest genetic potential for being tall of any of the populations, which is consistent with measurements of their ancient skeletons. In contrast, selection favored shorter people in Italy and Spain starting 8000 years ago, according to the paper now posted on the bioRxiv preprint server. Spaniards, in particular, shrank in stature 6000 years ago, perhaps as a result of adapting to colder temperatures and a poor diet.

Surprisingly, the team found no immune genes under intense selection, which is counter to hypotheses that diseases would have increased after the development of agriculture.

The paper doesn’t specify why these genes might have been under such strong selection. But the likely explanation for the pigmentation genes is to maximize vitamin D synthesis, said paleoanthropologist Nina Jablonski of Pennsylvania State University (Penn State), University Park, as she looked at the poster’s results at the meeting. People living in northern latitudes often don’t get enough UV to synthesize vitamin D in their skin so natural selection has favored two genetic solutions to that problem—evolving pale skin that absorbs UV more efficiently or favoring lactose tolerance to be able to digest the sugars and vitamin D naturally found in milk. “What we thought was a fairly simple picture of the emergence of depigmented skin in Europe is an exciting patchwork of selection as populations disperse into northern latitudes,” Jablonski says. “This data is fun because it shows how much recent evolution has taken place.”

Anthropological geneticist George Perry, also of Penn State, notes that the work reveals how an individual’s genetic potential is shaped by their diet and adaptation to their habitat. “We’re getting a much more detailed picture now of how selection works.”


An early cell shape transition drives evolutionary expansion of the human forebrain

The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla, and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that neuroepithelial differentiation is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition, associated with differences in interkinetic nuclear migration and cell cycle length. Comparative RNA sequencing (RNA-seq) reveals differences in expression dynamics of cell morphogenesis factors, including ZEB2, a known epithelial-mesenchymal transition regulator. We show that ZEB2 promotes neuroepithelial transition, and its manipulation and downstream signaling leads to acquisition of nonhuman ape architecture in the human context and vice versa, establishing an important role for neuroepithelial cell shape in human brain expansion.

Keywords: ZEB2 brain brain expansion cell shape chimpanzee evolution gorilla neural stem cells neuroepithelium organoids.

Copyright © 2021 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Human and ape stem cells and organoids are highly comparable in terms of…

Human telencephalic organoids are larger…

Human telencephalic organoids are larger with extended apical lumens (A) Schematic of the…

Ape NE cells undergo cell…

Ape NE cells undergo cell shape transition before the onset of neurogenesis, related…

Human NE cells exhibit species-specific…

Human NE cells exhibit species-specific differences in cell shape (A) Representative immunofluorescence images…

Delayed human NE transition is…

Delayed human NE transition is associated with a shorter cell cycle (A) Immunofluorescent…

Live imaging of human and…

Live imaging of human and gorilla cerebral organoids, related to Figure 3 Representative…

Ape organoids exhibit comparable developmental…

Ape organoids exhibit comparable developmental molecular trajectories (A) Schematic of the timeline for…

RNA-seq data analysis pipeline and…

RNA-seq data analysis pipeline and normalization, related to Figure 4 A. Workflow summarizing…

The human neuroepithelium exhibits differential…

The human neuroepithelium exhibits differential temporal dynamics of morphogenesis genes (A) Clustering genes…

Expression patterns of key factors…

Expression patterns of key factors with differential temporal dynamics, related to Figure 5…

Decreased ZEB2 leads to expanded…

Decreased ZEB2 leads to expanded NE with delayed transition (A) Mean temporal expression…

ZEB2 expression and targeting for…

ZEB2 expression and targeting for loss of function, related to Figure 6 A.…

50% reduction in ZEB2 mRNA levels the mutant stem cells retain expression of pluripotency markers at comparable levels to WT H9 hESCs. WT and ZEB2 +/− were run on the same gel but not adjacent to each other, the dashed line indicates where the gel was spliced. K. Full length western blot for ZEB2 in WT and ZEB2 +/− organoids at day 15 – loading control was GAPDH L. Box and whiskers plot reporting the quantifications of the number of TBR2+ cells per unit area (TBR2+ cells/mm 2 ) in day 16 WT and ZEB2 +/− organoids. Quantifications were performed by manual counting on n = 52 WT and n = 68 ZEB2 +/− ventricles corresponding to 12 organoids from 2 distinct batches. A two-tailed Mann-Whitney U test was used for statistical comparison ( ∗∗∗∗ p < 0.0001). M. Representative immunofluorescence images of day 55 WT and ZEB2 +/− cerebral organoid buds used for quantifications shown in N. Scale bar: 200 μm. N. Box and whiskers plot reporting the quantifications of the number of TBR2+ cells per unit area (TBR2+ cells/mm 2 ) in day 55 WT and ZEB2 +/− organoids. Quantifications were performed using an automated cell segmentation pipeline on n = 17 WT and n = 17 ZEB2 +/− organoid regions from 3 distinct batches. A two-tailed Mann-Whitney U test was used for statistical comparison (ns, p = 0.1139). O. Plasmid maps of the CRISPR homology-directed repair (HDR) templates used to target the AAVS1 safe-harbor locus in H9 hESC cells – top is the CAG-lox-STOP-lox-ZEB2-GFP-Flag inducible expression construct and bottom is the construct encoding CRE recombinase under the control of a tetracycline responsive promoter and the reverse tetracycline transactivator (rtTA) driven by the CAG promoter. P. UCSC Genome Browser view of the AAVS1 locus and CRISPR-Cas9 targeting strategy of intron 1 of PPP1R12C. The promoter-less splice-acceptor (SA), T2A peptide-linked “gene trap” is such that expression of the promoter-less selection cassette is driven by the endogenous PPP1R12C gene, thus effectively eliminating false-positive background arising from random integration. The panel reports the PCR genotyping strategy – upon successful targeting of the AAVS1 locus, while amplicon 1 is lost due to the size increase following insert integration, amplicons 2 and 3 are gained - see Figure S7A. Q. PCR gel showing successful genotyping of the two rescue clones used for the experiments shown. R. Representative brightfield images of day 15 ZEB2 +/− iZEB2 cerebral organoids treated with and without doxycycline. Scale bar: 100 μm. S. Representative immunofluorescence images of ZEB2 +/− iZEB2 treated with and without doxycycline stained for GFP, TBR2 and DAPI. Scale bar: 100 μm T. Box and whiskers plot reporting the quantifications done using an automated cell segmentation pipeline of the number of TBR2+ cells per unit area (TBR2+ cells/mm 2 ) in day 15 ZEB2 +/− iZEB2 organoids - colony 1: -Dox (n = 17 organoid regions), +Dox (n = 16 organoid regions) colony 2: -Dox (n = 13 organoid regions), +Dox (n = 13 organoid regions) from three independent batches. Mann-Whitney U tests, two-tailed ( ∗∗ p < 0.01).