Human brain size gene triggers bigger brain in monkeys

Microscopy image of a section through one brain hemisphere of a 101 day- old ARHGAP11B-transgenic marmoset fetus. Cell nuclei are visualized by DAPI (white). Arrows indicate a sulcus and a gyrus. Credit: Heide et al. / MPI-CBG

The expansion of the human brain during evolution, specifically of the neocortex, is linked to cognitive abilities such as reasoning and language. A certain gene called ARHGAP11B that is only found in humans triggers brain stem cells to form more stem cells, a prerequisite for a bigger brain. Past studies have shown that ARHGAP11B, when expressed in mice and ferrets to unphysiologically high levels, causes an expanded neocortex, but its relevance for primate evolution has been unclear.

Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, together with colleagues at the Central Institute for Experimental Animals (CIEA) in Kawasaki and the Keio University in Tokyo, both located in Japan, now show that this human-specific gene, when expressed to physiological levels, causes an enlarged neocortex in the common marmoset, a New World monkey. This suggests that the ARHGAP11B gene may have caused neocortex expansion during human evolution. The researchers published their findings in the journal Science.

The human neocortex, the evolutionarily youngest part of the cerebral cortex, is about three times bigger than that of the closest human relatives, chimpanzees, and its folding into wrinkles increased during evolution to fit inside the restricted space of the skull. A key question for scientists is how the human neocortex became so big. In a 2015 study, the research group of Wieland Huttner, a founding director of the MPI-CBG, found that under the influence of the human-specific gene ARHGAP11B, mouse embryos produced many more neural progenitor cells and could even undergo folding of their normally unfolded neocortex. The results suggested that the gene ARHGAP11B plays a key role in the evolutionary expansion of the human neocortex.

The rise of the human-specific gene

The human-specific gene ARHGAP11B arose through a partial duplication of the ubiquitous gene ARHGAP11A approximately five million years ago along the evolutionary lineage leading to Neanderthals, Denisovans, and present-day humans, and after this lineage had segregated from that leading to the chimpanzee. In a follow-up study in 2016, the research group of Wieland Huttner uncovered a surprising reason why the ARHGAP11B protein contains a sequence of 47 amino acids that is human-specific, not found in the ARHGAP11A protein, and essential for ARHGAP11B’s ability to increase brain stem cells.

Specifically, a single C-to-G base substitution found in the ARHGAP11B gene leads to the loss of 55 nucleotides from the ARHGAP11B messenger RNA, which causes a shift in the reading frame resulting in the human-specific, functionally critical 47 amino acid sequence. This base substitution probably happened much later than when this gene arose about 5 million years ago, anytime between 1.5 million and 500,000 years ago. Such point mutations are not rare, but in the case of ARHGAP11B its advantages of forming a bigger brain seem to have immediately influenced human evolution.

Wildtype (normal) and ARHGAP11B-transgenic fetal (101 days) marmoset brains. Yellow lines, boundaries of cerebral cortex; white lines, developing cerebellum; arrowheads, folds. Scale bars, 1 mm. Credit: Heide et al. / MPI-CBG

The gene’s effect in monkeys

However, it has been unclear until now if the human-specific gene ARHGAP11B would also cause an enlarged neocortex in non-human primates. To investigate this, the researchers in the group of Wieland Huttner teamed up with Erika Sasaki at the Central Institute for Experimental Animals (CIEA) in Kawasaki and Hideyuki Okano at the Keio University in Tokyo, both located in Japan, who had pioneered the development of a technology to generate transgenic non-human primates. The first author of the study, postdoc Michael Heide, traveled to Japan to work with the colleagues directly on-site.

They generated transgenic common marmosets, a New World monkey, that expressed the human-specific gene ARHGAP11B, which they normally do not have, in the developing neocortex. Japan has similarly high ethical standards and regulations regarding animal research and animal welfare as Germany does. The brains of 101-day-old common marmoset fetuses (50 days before the normal birth date) were obtained in Japan and exported to the MPI-CBG in Dresden for detailed analysis.

Michael Heide explains: “We found indeed that the neocortex of the common marmoset brain was enlarged and the brain surface folded. Its cortical plate was also thicker than normal. Furthermore, we could see increased numbers of basal radial glia progenitors in the outer subventricular zone and increased numbers of upper-layer neurons, the neuron type that increases in primate evolution.” The researchers had now functional evidence that ARHGAP11B causes an expansion of the primate neocortex.

Ethical consideration

Wieland Huttner, who led the study, adds: “We confined our analyses to marmoset fetuses, because we anticipated that the expression of this human-specific gene would affect the neocortex development in the marmoset. In light of potential unforeseeable consequences with regard to postnatal brain function, we considered it a prerequisite—and mandatory from an ethical point of view—to first determine the effects of ARHGAP11B on the development of fetal marmoset neocortex.”

The researchers conclude that these results suggest that the human-specific ARHGAP11B gene may have caused neocortex expansion in the course of human evolution.

More information: “Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset” Science (2020). … 1126/science.abb2401

Ape Fossils Shed New Light on Evolution of Bipedalism

The 12-million-year-old bones of a previously unknown species named Danuvius guggenmosi challenge the prevailing view about when and where our ancestors first started walking upright.


Researchers in Germany have discovered the fossilized bones of a previously unknown species of ape that appeared to walk upright, according to a study published yesterday (November 6) in Nature. The bones, which the team dated to nearly 12 million years ago, suggest that bipedalism might have evolved in a common ancestor of humans and other great apes living in Europe, and not in more-recent human ancestors in Africa as many researchers had assumed.

The finding “changes the why, when and where of evolution of bipedality dramatically,” study coauthor Madelaine Böhme, a paleobiologist at the University of Tübingen in Germany, tells Reuters.

There are many theories about the evolution of bipedalism, but many assumed that upright walking appeared in our ancestors about 6 million to 8 million years ago—possibly as an adaptation to a reduction in forest cover occurring in East Africa around the same time.

See “Exploding Stars Probably Didn’t Spur Hominins to Walk Upright”
The new set of bones, unearthed from a clay pit in Bavaria between 2015 and 2018, are around 11.62 million years old and belong to several baboon-size apes, members of a species researchers have named Danuvius guggenmosi. The limbs show an unusual combination of anatomical features indicative of an ability to move both by swinging through trees and by walking upright.

“It was astonishing for us to realise during the process of research how similar certain bones were to humans, as opposed to great apes,” Böhme says in a statement, The Guardian reports.

“Together, the mosaic features of D. guggenmosi arguably provide the best model yet of what a common ancestor of humans and African apes might have looked like,” writes Tracy Kivell, a paleoanthropologist at the University of Kent who was not involved in the work, in an accompanying commentary in Nature. “It offers something for everyone: the forelimbs suited to life in the trees that all living apes, including humans, still have, and lower limbs suited to extended postures like those used by orangutans during bipedalism in the trees.”

The fossils could help researchers study hominid evolution more generally, the authors write in their paper. “With a broad thorax, long lumbar spine and extended hips and knees, as in bipeds, and elongated and fully extended forelimbs, as in all apes (hominoids), Danuvius combines the adaptations of bipeds and suspensory apes, and provides a model for the common ancestor of great apes and humans.”

Early life on Earth may have existed as miniature droplets of jelly

By Michael Marshall

Blobs of simple carbon-based compounds could have been the precursors to the first living cells. A new study suggests that such droplets could have formed quickly and easily on the young Earth.

“We were able to find these interesting microdroplet structures that could be synthesised from prebiotically available resources,” says Tony Jia of the Tokyo Institute of Technology in Japan. “Maybe they weren’t the direct precursors to modern cells, but perhaps they could have had some effect or had a role in the emergence of initial life.”

All modern cells are surrounded by an outer wall called a membrane, which is made of long chain-like molecules called lipids. Given the ubiquity of these membranes, many researchers studying how life began have made simple membrane-lined spheres, which they say could mimic the first simple cells.

The droplets Jia and his colleagues made are different. “They don’t have an outer layer,” says Jia. “In that sense they’re membrane-less.”

The first cells?
The team made them from simple chemicals called alpha-hydroxy acids. These are made by the same processes that create amino acids, suggesting they were present on the early Earth, says team member Kuhan Chandru of the National University of Malaysia. “You can find them in meteorites as well.” He showed in 2018 that alpha-hydroxy acids link up to form complex molecules at a wide range of temperatures.

In the new study, the team simply dissolved the acids in water, then left them to dry out at 80 °C for a week – mimicking the conditions near a hot volcanic pond.

The acids turned into a thick jelly, because they had again formed complex molecules. When the researchers added water, the jelly formed hundreds of droplets a few micrometres across. Further experiments showed that crucial biological molecules, including protein and RNA, could enter the droplets and still perform their functions.

Cells without walls
Membrane-less droplets were a key element of the first popular hypothesis for life’s origin, which was set out by Russian biologist Alexander Oparin in the 1920s. However, the idea fell out of favour when it emerged that all cells have membranes.

The idea is now being re-assessed, says Kate Adamala of the University of Minnesota in Minneapolis. She suspects that life went through a “membrane-less stage” and that membranes only arose later.

Both droplets and membrane-based cells are a container for life’s components. This is crucial, says Adamala, because it keeps all the parts together, creating an individual organism from what would otherwise be a mess of chemicals.

But membranes are such good barriers that the first cells would have struggled to get food in and waste out, Adamala argues. So at the very beginning, membrane-less droplets would be better. “You don’t have to be shut off from the environment, because those droplets are permeable and you can have things diffusing in and out of them.”

Journal reference: PNAS, DOI: 10.1073/pnas.1902336116

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Unknown human relative discovered in Philippine cave, Homo luzonensis, that lived more than 50,000 years ago.

Remains from Callao Cave in the Philippines, including a foot bone, belong to a new hominin species, Homo luzonensis.Credit: Rob Rownd, UP-ASP Film Inst.

The human family tree has grown another branch, after researchers unearthed remains of a previously unknown hominin species from a cave in the Philippines. They have named the new species, which was probably small-bodied, Homo luzonensis.

The discovery, reported in Nature on 10 April1, is likely to reignite debates over when ancient human relatives first left Africa. And the age of the remains — possibly as young as 50,000 years old — suggests that several different human species once co-existed across southeast Asia.

The first traces of the new species turned up more than a decade ago, when researchers reported the discovery of a foot bone dating to at least 67,000 years old in Callao Cave on the island of Luzon, in the Philippines2. The researchers were unsure which species the bone was from, but they reported that it resembled that of a small Homo sapiens.

Further excavations of Callao Cave uncovered a thigh bone, seven teeth, two foot bones and two hand bones — with features unlike those of other human relatives, contends the team, co-led by Florent Détroit, a palaeoanthropologist at the National Museum of Natural History in Paris. The remains come from at least two adults and one child.

“Together, they create a strong argument that this is something new,” says Matthew Tocheri, a palaeoanthropologist at Lakehead University in Thunder Bay, Canada.

Hominin history
H. luzonensis is the second new human species to be identified in southeast Asia in recent years. In 2004, another group announced the discovery3 of Homo floresiensis — also known as the Hobbit — a species that would have stood just over a metre in height, on the Indonesian island of Flores.

But Détroit and his colleagues argue that the Callao Cave remains are distinct from those of H. floresiensis and other hominins — including a species called Homo erectus thought to have been the first human relative to leave Africa, some 2 million years ago.

Seven hominin teeth, including molars and premolars, were found in Callao Cave.Credit: Callao Cave Archaeology Project

The newly discovered molars are extremely small compared with those of other ancient human relatives. Elevated cusps on the molars, like those in H. sapiens, are not as pronounced as they were in earlier hominins. The shape of the internal molar enamel looks similar to that of both H. sapiens and H. erectus specimens found in Asia. The premolars discovered at Callao Cave are small but still in the range of those of H. sapiens and H. floresiensis. But the authors report that the overall size of the teeth, as well as the ratio between molar and premolar size, is distinct from those of other members of the genus Homo.

The shape of the H. luzonensis foot bones is also distinct. They most resemble those of Australopithecus — primitive hominins, including the famous fossil Lucy, thought not to have ever left Africa. Curves in the toe bones and a finger bone of H. luzonensis suggest that the species might have been adept at climbing trees.

Curves in the toe bones of H. luzonensis may have been adaptations for climbing.Credit: Callao Cave Archaeology Project

The researchers are cautious about estimating H. luzonensis’ height, because there are only a few remains to go on. But given its small teeth, and the foot bone reported in 2010, Détroit thinks that its body size was within the range of small H. sapiens, such as members of some Indigenous ethnic groups living on Luzon and elsewhere in the Philippines today, sometimes known collectively as the Philippine Negritos. Men from these groups living in Luzon have a recorded mean height of around 151 centimetres and the women about 142 centimetres.

The right fit
Researchers are split on how H. luzonensis fits into the human family tree. Détroit favours the view that the new species descends from a H. erectus group whose bodies gradually evolved into forms different from those of their ancestors.

“You get different evolutionary pathways on islands,” says palaeontologist Gerrit van den Bergh at the University of Wollongong in Australia. “We can imagine H. erectus arrives on islands like Luzon or Flores, and no longer needs to engage in endurance running but needs to adapt to spend the night in trees.”

But, given the species’ similarities to Australopithecus, Tocheri wonders whether the Callao Cave dwellers descended from a line that migrated out of Africa before H. erectus.

Genetic material from the remains could help scientists to identify the species’ relationship to other hominins, but efforts to extract DNA from H. luzonensis have failed so far. However, the bones and teeth were dated to at least 50,000 years old. This suggests that the species might have been roaming southeast Asia at the same time as H. sapiens, H. floresiensis and a mysterious group known as the Denisovans, whose DNA has been found in contemporary humans in southeast Asia.

“Island southeast Asia appears to be full of palaeontological surprises that complicate simple scenarios of human evolution,” says William Jungers, a palaeoanthropologist at Stony Brook University in New York.

Humans couldn’t pronounce ‘f’ and ‘v’ sounds before farming developed

By Alison George

Human speech contains more than 2000 different sounds, from the ubiquitous “m” and “a” to the rare clicks of some southern African languages. But why are certain sounds more common than others? A ground-breaking, five-year investigation shows that diet-related changes in human bite led to new speech sounds that are now found in half the world’s languages.

More than 30 years ago, the linguist Charles Hockett noted that speech sounds called labiodentals, such as “f” and “v”, were more common in the languages of societies that ate softer foods. Now a team of researchers led by Damián Blasi at the University of Zurich, Switzerland, has pinpointed how and why this trend arose.

They found that the upper and lower incisors of ancient human adults were aligned, making it hard to produce labiodentals, which are formed by touching the lower lip to the upper teeth. Later, our jaws changed to an overbite structure, making it easier to produce such sounds.

The team showed that this change in bite correlated with the development of agriculture in the Neolithic period. Food became easier to chew at this point, which led to changes in human jaws and teeth: for instance, because it takes less pressure to chew softer, farmed foods, the jawbone doesn’t have to do as much work and so doesn’t grow to be so large.

Analyses of a language database also confirmed that there was a global change in the sound of world languages after the Neolithic era, with the use of “f” and “v” increasing dramatically in recent millennia. These sounds are still not found in the languages of many hunter-gatherer people today.

This research overturns the prevailing view that all human speech sounds were present when Homo sapiens evolved around 300,000 years ago. “The set of speech sounds we use has not necessarily remained stable since the emergence of our species, but rather the immense diversity of speech sounds that we find today is the product of a complex interplay of factors involving biological change and cultural evolution,” said team member Steven Moran, a linguist at the University of Zurich, at a briefing about this study.

This new approach to studying language evolution is a game changer, says Sean Roberts at the University of Bristol, UK. “For the first time, we can look at patterns in global data and spot new relationships between the way we speak and the way we live,” he says. “It’s an exciting time to be a linguist.”

Journal reference: Science, DOI: 10.1126/science.aav3218

Scientists Have Witnessed a Single-Celled Algae Evolve Into a Multicellular Organism

by Fiona MacDonald

Most of us know that at some point in our evolutionary history around 600 million years ago, single-celled organisms evolved into more complex multicellular life.

But knowing that happened and actually seeing it happen in real-time in front of you is an entirely different matter altogether.

And that’s exactly what researchers from the George Institute of Technology and University of Montana have witnessed – and captured in the breathtaking, time-lapse footage below.

The evolution took just 50 weeks, and was triggered by the introduction of a simple predator.

In this incredible experiment, the team was trying to figure out exactly what drove single-celled organisms to become multicellular all those years ago.

One hypothesis is that it was predation that put selective pressure on single-celled organisms, causing them to become more complex.

So to test the validity of this in the lab, the team led by evolutionary biologist William Ratcliff, took populations of single-celled green alga Chlamydomonas reinhardtii.

They then put a single-celled filter-feeding predator in the mix, Paramecium tetraurelia and watched what happened.

Incredibly, the researchers watched as in just 50 weeks – less than the span of a year – two out of five experimental populations of the single-celled creatures evolved into multicellular life.

“Here we show that de novo origins of simple multicellularity can evolve in response to predation,” the team write in their paper.

Fifty weeks is a relative blink of an eye on the evolutionary scale. For the algae it was a little longer – 750 generations. But that’s still quite impressive when you think that they evolved entirely new life cycles.

Being able to witness something like this is not only absolutely mind-blowing, but it also suggests that predation could have played some kind of role in at least part of the evolution of multicellularity.

Not only that, but the resulting multicellular organisms were all incredibly varied. Just like you’d expect in natural evolution.

“Considerable variation exists in the evolved multicellular life cycles, with both cell number and propagule size varying among isolates,” the team write in their paper.

“Survival assays show that evolved multicellular traits provide effective protection against predation.”

The research has been published in Scientific Reports and the full paper is freely available.

For The First Time, Scientists Have Made Synthetic DNA With 4 Additional Letters

by Mike McRae

Earth might have a dizzying array of life forms, but our biology ultimately remains a solitary data point – we simply don’t have a reference for life based on DNA different from our own. Now, scientists have taken matters into their hands to push the boundaries on what life could be like.

Research funded by NASA and led by the Foundation for Applied Molecular Evolution in the US has led to the creation of an entirely new flavour of the DNA double helix, one that has an additional four nucleotide bases.

It’s being called hachimoji DNA (from the Japanese words for ‘eight letters’) and it includes two new pairs to add to the existing partnerships of adenine (A) paired with thymine (T), and guanine (G) with cytosine (C).

This work to expand on nature’s own genetic recipe might sound a little familiar. The same scientists already successfully squeezed in two new letters in 2011. Only last year yet another version of an extended alphabet, also with six letters, was made to function inside a living organism.

Now, in what might seem like a case of overachievement, researchers have gone back to the drawing board to develop even more non-standard nucleotides.

They have a purpose for doubling the number of codes in the recipe book, though.

“By carefully analysing the roles of shape, size and structure in hachimoji DNA, this work expands our understanding of the types of molecules that might store information in extraterrestrial life on alien worlds,” says chemist Steven Benner.

We already know a lot about the stability and functionality of ‘natural’ DNA under a range of environmental conditions, and are slowly teasing apart possible scenarios describing its evolution from simpler organic materials to living chemistry.

But to really get a good sense of how a genetic system could evolve, we need to test the limits of its underlying chemistry.

Hachimoji DNA certainly allows for that. The new codes, labelled P, B, Z and S, are based on the same kind of nitrogenous molecules as existing ones, categorised as purines and pyrimidines.

Similarly, they link up with hydrogen bonds to form their own base pairs – S bonding with B, and P with Z.

That’s where the similarities fade out. These new ‘letters’ introduce dozens of new chemical parameters to the double helix structure that potentially affect how it zips and twists.

By devising models that predict the molecule’s stability and then observing actual structures made of this ‘alien’ DNA, researchers are better equipped what’s truly important when it comes to the fundamentals of a genetic template.

The researchers constructed hundreds of hachimoji helices made up of different configurations of natural and synthetic bases and then subjected them to a range of conditions to see how well they held up.

While there were a few minor differences in how the new letters behaved, there was no reason to believe hachimoji DNA wouldn’t work well as an information-carrying template that could mutate and evolve.

The team not only showed their synthetic letters could contribute to new codes without swiftly disintegrating, the sequences were also translated into synthetic RNA versions.

Their work falls well short of a second genesis. But a novel DNA format such as this is a step towards determining what living chemistry might – and might not – look like elsewhere in the Universe.

“Life detection is an increasingly important goal of NASA’s planetary science missions, and this new work will help us to develop effective instruments and experiments that will expand the scope of what we look for,” says NASA’s Planetary Science Division’s acting director, Lori Glaze.

Devising new bases that can operate alongside our own DNA also has applications closer to home, not only as a way to reprogram life with a different code base, but in our effort to build new kinds of nanostructures.

The sky really isn’t the limit with synthetic DNA. This is going to take us to the stars and back again.

This research was published in Science.

Researchers have discovered a gene that has evolved through natural selection to impact both psychiatric disorders and personality, and may help to maintain human diversity.


How and why human-unique characteristics such as highly social behavior, languages and complex culture have evolved is a long-standing question. A research team led by Tohoku University in Japan has revealed the evolution of a gene related to such human-unique psychiatric traits.

PhD candidate Daiki Sato and Professor Masakado Kawata have discovered SLC18A1 (VMAT1), which encodes vesicular monoamine transporter 1, as one of the genes evolved through natural selection in the human lineage. VMAT1 is mainly involved in the transport of neurochemicals, such as serotonin and dopamine in the body, and its malfunction leads to various psychiatric disorders. VMAT1 has variants consisting of two different amino acids, threonine (136Thr) and isoleucine (136Ile), at site 136.

Several studies have shown that these variants are associated with psychiatric disorders, including schizophrenia, bipolar disorder, anxiety, and neuroticism (a personality trait). It has been known that individuals with 136Thr tend to be more anxious and more depressed and have higher neuroticism scores. They showed that other mammals have 136Asn at this site but 136Thr had been favored over 136Asn during human evolution. Moreover, the 136Ile variant had originated nearly at the Out-of-Africa migration, and then, both 136Thr and 136Ile variants have been positively maintained by natural selection in non-African populations.

The study by Sato and Kawata indicates that natural selection has possibly shaped our psychiatric traits and maintained its diversity. The results provide two important implications for human psychiatric evolution. First, through positive selection, the evolution from Asn to Thr at site 136 on SLC18A1 was favored by natural selection during the evolution from ancestral primates to humans, although individuals with 136Thr are more anxious and have more depressed minds.

Second, they showed that the two variants of 136Thr and 136Ile have been maintained by natural selection using several population genetic methods. Any form of natural selection that maintains genetic diversity within populations is called “balancing selection”. Individual differences in psychiatric traits can be observed in any human population, and some personality traits are also found in non-human primates. This suggests the possibility that a part of genetic diversity associated with personality traits and/or psychiatric disorders are maintained by balancing selection, although such selective pressure is often weak and difficult to detect.

The Evolution of Psychiatric Disorders and Personality Traits

Scientists have found that our big toe was one of the last parts of the foot to evolve

As our early ancestors began to walk on two legs, they would also have hung about in trees, using their feet to grasp branches. They walked differently on the ground, but were still able to move around quite efficiently. The rigid big toe that eventually evolved gives efficient push-off power during walking and running.

The findings have been published in the journal Proceedings of the National Academy of Sciences.

In this new study, scientists made 3D scans of the toe bone joints from living and fossil human relatives, including primates such as apes and monkeys, and then compared them to modern day humans.

They overlaid this information onto an evolutionary tree, revealing the timing and sequence of events that produced the human forefoot.

The main finding is that the current shape of the bones in the big toe, or “hallux” in anatomical language, must have evolved quite late in comparison with the rest of the bones that they investigated.

In an interview with the BBC, lead author of the study Dr Peter Fernandez, from Marquette University in Milwaukee, said: “Our ability to efficiently walk and run on two feet, or be ‘bipedal’, is a crucial feature that enabled humans to become what they are today. For everything to work together, the foot bones first had to evolve to accommodate the unique biomechanical demands of bipedalism”.

He then said: “The big toe is mechanically very important for walking. In our study, we showed that it did not reach its modern form until considerably later than the other toes.”

When asked whether the rigid big toe evolved last because it is most or least important, Dr Fernandez commented: “It might have been last because it was the hardest to change. We also think there was a compromise. The big toe could still be used for grasping, as our ancestors spent a fair amount of their time in the trees, before becoming fully committed to walking on the ground.”

He added: “Modern humans have increased the stability of the joint to put the toe in an orientation that is useful for walking, but the foot is no longer dextrous like an ape.”vvvv

The reason that our ancestors stood upright and then walked on two feet is still a mystery, but there are plenty of ideas. Scientists think that walking may have evolved, either because it freed our hands to carry tools, or because climate change led to a loss of forests, or that overhead arms can be used to support walking on two legs along thin branches.

Studies such as this new one show that early human ancestors must have able been to walk upright for millions of years, since the 4.4 million year old fossil Ardipithecus ramidus, but that they did not fully transition to a modern walk until much later, perhaps in closer relatives within our own group, Homo.

This new study, alongside other work, now confirms that early walking humans, or “hominins” still used their feet to grasp objects.

Dr William Harcourt-Smith from City University of New York, who was not involved in this study, said: “They are suggesting that one of the earliest hominins, Ardipithecus, was already adapting in a direction away from the predicted morphology of the last common ancestor of chimps and modern humans, but not ‘towards’ modern humans. To me this implies that there were several lineages within hominins that were likely experimenting with bipedalism in different ways to each other.”

Professor Fred Spoor, an expert in human anatomy at the Natural History Museum, London said: “It was a bit of shock when hominins were found that have a grasping, or opposable, big toe, as this was thought to be incompatible with effective bipedalism. This work shows that different parts of the foot can have different functions. When a big toe is opposable, you can still function properly as a biped.”

The scientists involved say that this work shows that early hominin feet had a mixed and versatile set of functions. Becoming human was not a giant step, but a series of gradual changes, with some of the last and arguably most important changes being made to big toes. Peter Fernandez said that they would like to conduct similar analyses on the remaining bones of the forefoot, in order to fully characterise the changes involved in the evolution of bipedal walking.

Genetic Adaptation to Cold Brought Migraines With It

Frequency of the adaptive allele in several human populations (from the 1000 Genomes dataset). Colors and letters represent different populations in the dataset, and the pie charts reflect the proportion of individuals in those populations who have the variant TRPM8 allele.

By Viviane Callier

A human genetic variant in a gene involved in sensing cold temperatures became more common when early humans migrated out of Africa into colder climates between 20,000 and 30,000 years ago, a study published May 3 in PLOS Genetics shows. The advantage conferred by this variant isn’t definitively known, but the researchers suspect that it influences the gene’s expression levels, which in turn affect the degree of cold sensation. The observed pattern of positive selection strongly indicates that the allele was beneficial, but that benefit had a tradeoff—bringing with it a higher risk of getting migraines.

“This paper is the latest in a series of papers showing that humans really have adapted to different environments after some of our ancestors migrated out of Africa,” explains evolutionary geneticist Rasmus Nieslen of the University of California, Berkeley, who was not involved in the study. “There are a number of adaptations associated with moving into an artic climate, but none with as clear a connection to cold as this one,” he adds.

Although studies have demonstrated some striking examples of recent human adaptation, for instance, warding off infectious diseases such as malaria or having the ability to digest milk, relatively little was known about the evolutionary responses to fundamental features of the environment, namely, temperature and climate.

“Obviously, humans lived in Africa for a long time, and one of the main environmental factors that changed as humans migrated north was temperature,” explains population geneticist Aida Andres. So she and Felix Key the Max Planck Institute in Leipzig homed in on a gene, TRPM8, that encodes a cation channel in the neurons that innervate the skin. It is activated by cold temperatures and necessary for sensing cold and for thermoregulation. If there was a place to look for human adaptation, this gene looked like a good candidate.

Using the 1000 Genomes dataset and the Simons Genome Diversity Panel, the researchers investigated variants of this gene in populations throughout Africa, Europe, and Asia. They found that a single nucleotide polymorphism (SNP) in a regulatory region of the TRPM8 gene was “highly differentiated between different populations in the world,” Andres, now at University College London, says. And genotype correlated with latitude: 5 percent of people with Nigerian ancestry, versus 88 percent of people with Finnish ancestry, carry the cold-adapted variant.

Using models of population genetics, the researchers inferred that the cold-adapted allele had already existed in the ancestral African population, and that it became more common as people migrated northward. The geographic pattern was consistent with positive selection for the SNP at higher latitudes, Andres says.

“One of the interesting things about [this variant] is that it is relatively more common in Europe than in Asian people who live at the same latitude,” notes Hawks. “We don’t know why that should be. Maybe there’s a historical factor here that isn’t yet understood.”

To find out when selection on this variant occurred, the researchers looked for the SNP in the genomes from ancient remains of hunter gatherers or farmers that lived 3,000–8,000 years ago in Eurasia. It turned out that the allele was already common among these groups at least 3,000 years ago.

The connection between TRPM8 and migraine isn’t clear, other than the association. “Selection is optimizing fitness,” says anthropologist John Hawks of the University of Wisconsin-Madison who was not associated with the study. “It doesn’t optimize health, it doesn’t optimize happiness, so sometimes things are pushed by selection and they have negative side effects. This seems to be a case where a gene is pushed higher in frequency by selection for adaptation to cold, and it maybe has a bad side effect on increased susceptibility to migraines.” It’s also possible that the downside to having the cold-adaptive TRPM8 allele is a modern phenomenon, and that the migraine risk didn’t appear until more recently as environments have changed, says Nielsen.

F.M. Key et al., “Human local adaptation of the TRPM8 cold receptor along a latitudinal cline. PLOS Genet, 14:e1007298, 2018.