In a study published Aug. 5 in Nature, an interdisciplinary, international team of researchers, in partnership with M?ori tribe Ng?tiwai, sequenced, assembled and analyzed the complete genome of the Sphenodon punctatus, or the tuatara, a rare reptile whose ancestors once roamed the earth with dinosaurs. It hasn’t changed much in the 150 million to 250 million years since then.

“We found that the tuatara genome has accumulated far fewer DNA substitutions over time than other reptiles, and the molecular clock for tuataras ticked at a much slower speed than squamates, although faster than turtles and crocodiles, which are the real molecular slowpokes,” said co-author Marc Tollis, an assistant professor in the School of Informatics, Computing, and Cyber Systems at Northern Arizona University. “This means in terms of the rate of molecular evolution, tuataras are kind of the Toyota Corolla — nothing special but very reliable and persistently ticking away over hundreds of millions of years.”

Tuatara have been out on their own for a staggering amount of time, with prior estimates ranging from 150-250 million years, and with no close relatives the position of tuatara on tree of life has long been contentious. Some argue tuatara are more closely related to birds, crocodiles and turtles, while others say they stem from a common ancestor shared with lizards and snakes. This new research places tuatara firmly in the branch shared with lizards and snakes, but they appear to have split off and been on their own for about 250 million years — a massive length of time considering primates originated about 65 million years ago, and hominids, from which humans descend, originated approximately six million years ago.

“Proving the phylogenetic position of tuatara in a robust way is exciting, but we see the biggest discovery in this research as uncovering the genetic code and beginning to explore aspects of the biology that makes this species so unique, while also developing new information that will help us better conserve this taonga or special treasure,” said lead author Neil Gemmell, a professor at the University of Otago.

One area of particular interest is to understand how tuataras, which can live to be more than 100 years old, achieve such longevity. Examining some of the genes implicated in protecting the body from the ravages of age found that tuatara have more of these genes than any other vertebrate species thus far examined, including humans. This could offer clues into how to increase humans’ resistance to the ailments that kill humans.

But the genome, and the tuatara itself, has so many other unique features all on its own. For one, scientists have found tuatara fossils dating back 150 million years, and they look exactly the same as the animals today. The fossil story dates the tuatara lineage to the Triassic Period, when dinosaurs were just starting to roam the Earth.

“The tuatara genome is really a time machine that allows us to understand what the genetic conditions were for animals that were vying for world supremacy hundreds of millions of years ago,” he said. “A genome sequence from an animal this ancient and divergent could give us a better idea about what the ancestral amniote genome might have looked like.”

While modern birds are the descendants of dinosaurs, they are less suitable for this type of research because avian genomes have lost a significant amount of DNA since diverging from their dinosaur ancestors.

But the tuataras, which used to be spread throughout the world, have other unusual features. Particularly relevant to this research is the size of its genome; the genome of this little lizard has 5 billion bases of DNA, making it 67 percent larger than a human genome. Additionally, tuataras have temperature-based sex determination, which means the ratio of males to females in a clutch of eggs depends on the temperatures at which they are incubated. They also have a pronounced “third eye” — a light sensory organ that sticks through the top of their skulls. Mammals’ skulls have completely covered the third eye, though they still contain the pineal gland underneath, which helps maintain circadian rhythms.

The tuatara also is unique in that it is sacred to the M?ori people. This research, for all the scientific knowledge that came from it, was groundbreaking for its collaboration with the Indigenous New Zealanders. The purpose was to ensure the research aligned with and respected the importance of the tuatara in their culture, which has never been done before in genomic research.

“Tuatara are a taonga, and it’s pleasing to see the results of this study have now been published,” Ng?tiwai Trust Board resource management unit manager Alyx Pivac said. “Our hope is that this is yet another piece of information that will help us understand tuatara and aid in the conservation of this special species. We want to extend a big mihi to all of those who have been involved in this important piece of work.”

With the genome now sequenced, the international science community has a blueprint through which to examine the many unique features of tuatara biology, which will aid human understanding of the evolution of the amniotes, a group that includes birds, reptiles and mammals.

In fact, the geometry of quantum states is one of the central concepts underlying diverse physical phenomena, ranging from the celebrated Aharonov-Bohm effect to the topological phases of matter developed more recently. For instance, the local Berry curvature is responsible for the anomalous Hall transport while its integral over a two-dimensional closed manifold gives the Chern number, an integer number describing the quantized Hall conductivity. However, compared to the physics of the Berry curvature, the effects of the quantum metric on physical phenomena are less understood, especially in solids, although there are several recent works proposing the physical observables related to the quantum metric. Especially, there has been no clear guideline for searching materials in which the physical properties related with the quantum metric can be observed.

Prof. YANG Bohm-Jung and Dr. RHIM Jun-Won at the Center for Correlated Electron Systems within the Institute for Basic Science (IBS) in Seoul National University, Seoul, South Korea, and Dr. KIM Kyoo at the Korea Atomic Energy Research Institute, Daejeon, South Korea, reported that they found a way to measure the quantum distance of Bloch states in solids by applying magnetic field. More specifically, the researchers have examined the energy spectrum under magnetic field, called the Landau level spectrum, of flat bands in the kagome and checkerboard lattices, and observed anomalous Landau level spreading arising from the flat band. Surprisingly, they found that the total energy spreading of the flat band’s Landau level is solely determined by the maximum quantum distance between the Bloch states of the flat band. Namely, the quantum distance of the Bloch states in solid can be measured by applying magnetic field to two-dimensional materials with flat bands!

Recently, two-dimensional materials with flat bands have received a great attention as a new platform to realize intriguing electronic states. A flat band indicates an electronic band structure in which the energy does not change when crystal momentum is varied. Such intriguing flat band structures appear in various two-dimensional lattices including the kagome lattice, checkerboard lattice, etc. The theory group of the IBS CCES research team realized that, in many of the flat band systems, the Berry curvature of the Bloch states is zero due to the symmetry of the lattice. If the Berry curvature is strictly zero, one can naturally expect that the geometry of the Bloch states is solely determined by the quantum metric. This interesting aspect motivated the IBS theory team to seriously consider two-dimensional materials with flat bands as a promising playground to study physical properties related to the quantum metric.

In fact, the semiclassical quantization rule predicts that an ordinary parabolic band under magnetic field forms equally-spaced discrete Landau levels, and the energy difference between neighboring Landau levels is inversely proportional to the effective mass of the electrons. When applied to a flat band with an infinite effective mass, the semiclassical theory predicts zero Landau level spacing so that a flat band remains inert under magnetic field. In this study, the researchers observed a quite peculiar nature of the Landau level spectrum that is in sharp contrast to the conventional norm. They reported that the Landau levels of the flat bands spread into the empty region of the energy space where no electronic states are available in the absence of magnetic field.

The researchers found that the key to such an unusual Landau level spectrum is the fact that the flat band in the kagome and checkerboard lattices is crossing with another parabolic band at a point. The singularity in the wave function of the flat band arising from the band crossing point induces nontrivial geometric effect related to the quantum distance of the wave function, which in turn induces anomalous Landau level spectrum. The first author, Dr. RHIM Jun-Won states, “Understanding the role of the band crossing in flat bands was the key to describe the anomalous Landau levels. This finding provides a practical way to unambiguously extract the quantum distance in solids.”

This study shows that the quantum distance or quantum metric can also play crucial roles in determining material properties as the Berry curvature does. Contrary to the previous works, this study clearly identified the candidate lattice systems in which the quantum metric effect is maximized while the Berry curvature effect is minimized, and discovered a way to directly extract the quantum distance in solids for the first time. Considering the tremendous impact of the concept of the Berry curvature on the understanding the properties of solids, it is natural to expect that this study may facilitate the future study about the geometric properties of solids related to the quantum metric and the search of materials in which the related physical responses can be observed.

Prof. YANG Bohm-Jung explains that “This result would provide a critical step towards the complete understanding of geometrical properties of quantum states in solids. As there are many two-dimensional lattice structures hosting flat bands, our study may trigger future research activities for discovering novel geometrical phenomena related to the quantum metric in various condensed matter materials.”

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Cancer cells differ from healthy body cells — in their appearance, their behavior and the genes that are active in them. Often this does not go unnoticed: The immune system registers that something is wrong and dispatches its troops to fight the tumor. However, this response is often too weak to keep the cancer in check in the long term or even destroy it.

Researchers have therefore been trying for many years to strengthen the immune system’s defensive reaction. They do this in a similar way to a policeman who puts his dog on the trail of an escaped criminal. In this case, the role of the sniffer dog is taken over by the cytotoxic T cells: They can detect and kill sick or defective cells. Each T cell is directed against a specific characteristic, also called antigen. For cancer therapy, the researchers are therefore looking for T cells in patients that detect tumor antigens. They can then for instance multiply these and inject them back into the patient. In this way they strengthen the patient’s immune response against the cancer.

However, many tumors have unfortunately developed strategies that enable them to evade the immune system. “In our study, we investigated what these strategies look like and what this depends on,” explains Dr. Maike Effern from the Institute of Experimental Oncology at the University Hospital Bonn. “We focused on skin cancer, namely melanoma cells.”

Melanomas differ from healthy cells in several ways. For example, a whole range of different genes are active in them. Each of these is a potential antigen for T cells. But which is particularly suitable for triggering a strong and lasting immune response? To answer this question, the researchers invented a clever method in their experimental model: They attached a kind of label to various genes that are active in the development of melanoma cells and used them to produce antigens. They then released a group of T cells against the tumor cells, which recognized exactly this molecular label as a disease marker. The researchers then used this strategy to investigate how the cancer cells react to being pursued by the immune system. Depending on the gene tagged with such a label, they found significant differences.

Cancer cells hide from the immune system

“When the T cells were directed against genes responsible for melanoma-typical characteristics, we observed that the cancer cells changed their appearance and suppressed these genes over time,” explains Effern’s colleague Dr. Nicole Glodde. “So this is how they hide from the immune system.”

In contrast, another gene investigated in the study is essential for the tumor’s survival. This makes it not so easy to downregulate and thus hide. “In our view, this gene therefore has the potential to induce a very effective T cell response,” Effern emphasizes. “Our work potentially clears the way to more effective immune therapies,” hopes Prof. Dr. Michael Hölzel, head of the Institute of Experimental Oncology at the University Hospital Bonn and member of the Cluster of Excellence ImmunoSensation at the University of Bonn. “The method we have developed also makes it possible to better understand the processes by which cancer cells slip under the radar of the immune system.”

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