August 2018 – More Than A Dodo

How we got bigger, more vulnerable brains

This article is taken from European research magazine Horizon as part of our partnership to share natural environment science stories with readers of More than a Dodo. For more on the development of the brain see our Brain Diaries exhibition site.

One of the major features that distinguishes humans from other primates is the size of our brains, which underwent rapid evolution from about two to three million years ago in a group of our ancestors in Africa called the Australopithecines. During this period, the human brain grew almost three-fold to reach its current size. Scientists know this from skull remains, but have puzzled over how it happened…

This year, the mystery was partially solved by Professor Pierre Vanderhaeghen at the Flanders Institute for Biotechnology in Belgium. Prof. Vanderhaeghen, who was conducting his work as part of the GENDEVOCORTEX project, went on a hunt for the genes that drove the growth of human brains.

Scientists had suspected that brain expansion began in our human ancestors when they evolved genes that are switched on in the foetus, when a lot of key brain development occurs. Prof. Vanderhaeghen therefore looked for genes present in human foetal tissue, but missing from our closest living relatives, apes.

His lab discovered 35 hominid – present only in apes and humans – genes that were active in foetal brain tissue. They then became intrigued by three specific genes – all similar to NOTCH genes, an ancient gene family involved in sending messages between cells and that are present in all animals. They found that the three new genes, collectively named NOTCH 2NL, were created by a “copy and paste error” of an original NOTCH gene.

This error created entirely new proteins which likely helped our ancestors’ cerebral cortex to balloon. This is the part of our brain responsible for our language, imagination and problem-solving abilities. Scientists at the University of California, Santa Cruz, have also identified the NOTCH 2NL genes in DNA from Homo sapiens’ extinct cousins – the Neanderthals and Denisovans.

(The NOTCH 2NL) genes are only present in humans today. They were also present in Neanderthal DNA, but not in chimpanzees
Prof. Vanderhaeghen

Evolution
These genes control the growth rate and differentiation of brain stem cells – the starter cells that multiply and give rise to all neurons in our brain – causing them to seed more nerve cells, which in turn helped to expand brain size. The genes likely led to more neurons and brain tissue in our ancestor’s descendants – including Neanderthals, Denisovans, and modern humans.

Prof. Vanderhaeghen’s research could also help to provide new insights into brain disorders. The US researchers linked genetic faults in DNA that were very similar to NOTCH 2NL, to children born with enlarged brains or small brains. Many of the new human-specific genes are located in a small area of our genome that plays an important role in brain size, according to Prof. Vanderhaeghen.

As DNA in this area closely resembles another part of the genome where it was originally cut and pasted from millions of years ago, errors are more likely, said Prof. Vanderhaeghen. “Patients who have (inherited) deletions in this area tend to be at risk of developing schizophrenia, whereas patients with duplications are more at risk of autistic spectrum disorder,” he said.

Prof. Vanderhaeghen is now studying some 20 of the remaining human-only genes to see how they contributed to the evolution of the human brain.

Something like 40-50% of the Neanderthal genome can still be found in people today.
Prof. Svante Pääbo, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany

The use of genetics to study human evolution in this way is helping to transform our understanding of how our own species compared to our ancestors. Traditionally, scientists have studied extinct species by looking at the fossilised remains of their bones. This was how they discovered the existence of Neanderthals, the extinct human species that lived across Europe and much of Asia before vanishing around 40,000 years ago.

In the last decade, however, scientists have begun to look at the DNA inside these bones. Professor Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, has led the way in sequencing DNA of these extinct humans from small bone fragments.

This allows scientists to compare modern human DNA with that of extinct humans, rather than just living relatives like chimps. Already, the work has revealed some surprising findings – our own species appears to have interbred with some of these ancient relatives during our history.

Ancient humans
Scientists have found that the DNA of every person outside Africa is 1-2% Neanderthal, meaning that these extinct human relatives had offspring with our own ancestors.

An international consortium of researchers is sequencing the 3 billion bases that make up the genome of our closest relative – the Neanderthal. The sequence is generated from DNA extracted from three Croatian Neanderthal fossils using novel methods developed for this project. Image credit – Frank Vinken for Max Planck Society

“Different people tend to carry different pieces of the Neanderthal genome,” said Prof. Pääbo, who is undertaking a project called 100 Archaic Genomes to decipher the DNA of ancient human individuals. “Something like 40-50% of the Neanderthal genome can still be found in people today,” he said.

According to Prof. Pääbo, we retained some of this DNA because it offered an advantage to our ancestors. “Some (of this retained DNA) has to do with the immune system, presumably helping us to fight off infectious diseases.”

The power of genetics to unravel the history of human evolution took a new twist in 2010 after Prof. Pääbo’s lab sequenced DNA from a finger bone fragment found by a Russian archaeological team in a remote Siberian cave.

The analysis revealed the bone belonged to a previously unknown human relative, now called Denisovans after Denisova Cave where the bone was found. This mysterious ancient human species lived at around the same time as Neanderthals, but further east into Asia.

Last year, Prof. Pääbo’s group published DNA sequences from a tooth found in the cave – the fourth ever Denisovan discovered. We now know Denisovan DNA carries more variation than Neanderthal DNA, leading scientists to conclude that they were more widespread than the better-known Neanderthals.

Denisovans left a more impressive stamp on some of us than Neanderthals, according to Prof Pääbo. Their DNA can be found in people across Asia today, while indigenous peoples of Papua New Guinea and Australia may carry up to 5%. Tibetans also carry some Denisovan DNA in their genomes, which has helped them adapt to life at high altitudes where there is little oxygen in the atmosphere.

Prof. Pääbo and his colleagues will soon publish their third high-quality genome – where almost the entire DNA sequence is intact – of a Neanderthal from Siberia. A deciphered genome of this quality allows for better DNA comparisons and could tell us more about the evolution of important genes – such as those linked to the development and function of the brain. It will add yet another puzzle piece to help us understand the history of our closest extinct relatives, according to Prof. Pääbo.

“There may even be other forms of extinct humans out there to be discovered by studying the DNA of the (ancient) bones we find,” he said.

Top image: The skull of a Australopithecus sediba, a species of Australopithecines, who were our ancestors and whose brains started to grow two to three million years ago. Image credit – Australopithecus sediba by Brett Eloff, courtesy Profberger and Wits University is licensed under CC BY-SA 4.0.

This post Genetic error led humans to evolve bigger, but more vulnerable, brains was originally published on Horizon: the EU Research & Innovation magazine | European Commission.

From pin to paper

Katherine Child, image technician in the Museum’s Life collections, doesn’t just use photography to capture the beauty of specimens. She is also an artist and has been trying out innovative techniques for her paintings. You may remember her amazing moth illustrations created with deposits of verdigris on pinned insects and she’s now using that technique to explore Museum staff’s favourite insect specimens.

Verdigris is a green corrosion often found on old pins within entomology collections (as well as elsewhere, on things like statues and copper pipes). Last year, after learning that the substance was once used as a pigment, I decided to try and make my own paint.

A clearwing moth before conservation, showing verdigris spreading where metal reacts with insect fats, or lipids.

Verdigris forms when copper or a copper alloy reacts with water, oxygen, carbon dioxide or sulphur. While a beautiful shade of green, the substance is damaging in natural history collections, where it can actually develop inside specimens and if left, split them irreversibly. So as part of the conservation of the Hope Entomological Collections, verdigris is removed.

I started to collect up the substance as it was cleaned from specimens and after about three years (you only get a little bit per pin) I was ready to make my paint! After my first moth project, the only question was, what to paint next…?

Attelabid_small — *Byctiscus populi* or ‘The Attelabid that changed my life’, chosen by Zoë (collections manager) who said ‘I saw a pink version of this species in the Natural History Museum in London and that’s when I decided I wanted to study entomology’.

With an estimated 6 million insects and arachnids in the entomology collections, it’s very easy to feel overwhelmed. You can pull open any one of thousands of draws and find astonishing specimens. While I have favourites, my first inclinations as to what to paint still felt a little arbitrary. After mulling over various possibilities, I decided to get help!

Chosen by DPhil student Leonidas, *Agalmatium bilobum* is a little bug which lays its eggs on tree bark, then covers them with mud to protect them.

I asked my co-workers what their favourite insects were, then opened the question out to regular volunteers and visitors of the Life collections. I loved finding out why people chose the things they did. Answers varied from ‘It was the first spider I ever looked at under a microscope aged 12’ to ‘Because they’re cool’ to ‘Because they have an ingenious way of manipulating spiders!’

Nuctenea_small — One of arachnologist Russell’s favourite spiders: *Nuctenea umbratica*. Though common in the UK, umbratica is Latin for “living in the shadows”, and it often hides away during the day. The slight transparency of the paint lends itself to a spider’s glittering eyes.

Painting this live African Mantis *Sphodromantis lineola* (chosen by conservator Jackie) was made slightly more challenging by the fact that the subject thought Katherine’s pencil might be tasty.

Most of the subjects I painted were based on specimens from the Museum’s collections or specimens individuals had brought in from their own collections, but one favourite was a live African Mantis, housed in the department to help with education and outreach. When I began to draw her she was intrigued by the movement of my pencil and came to the front of the tank, to follow every mark I made with her intimidating gaze.

Attelabid that... — Katherine’s fabulous finished painting, which will be framed and displayed in the Life collections department.

Though time consuming, the painting was loads of fun to research and do. It’s fantastic to be surrounded not only by extremely knowledgeable people, but also by people with a genuine passion for what they do and a love for the insects (and spiders) they study.