Genetics biweekly vol.49, 2nd December — 15th December
TL;DR
- The complexity of living organisms is encoded within their genes, but where do these genes come from? Researchers resolved outstanding questions regarding the origin of small regulatory genes, and described a mechanism that creates their DNA palindromes. Under suitable circumstances, these palindromes evolve into microRNA genes.
- In order for immune cells to do their job, they need to know against whom they should direct their attack. Research teams a have identified new details in this process.
- Viruses have limited genetic material — and few proteins — so all the pieces must work extra hard. Zika is a great example; the virus only produces 10 proteins. Now researchers have shown how the virus does so much with so little and may have identified a therapeutic vulnerability.
- Researchers have shown that an influx of water and ions into immune cells allows them to migrate to where they’re needed in the body.
- Scientists have discovered that electric eels can alter the genes of tiny fish larvae with their electric shock. Their findings help to better understand electroporation, a method by which genes can be transported using electricity.
- Researchers have uncovered the intricate molecular mechanism used by parasitic phytoplasma bacteria, known for inducing ‘zombie-like’ effects in plants.
- Aquaporins, which move water through membranes of plant cells, were not thought to be able to permeate sugar molecules, but researchers have observed sucrose transport in plant aquaporins for the first time, challenging this theory.
- Scientists have amassed genome data for dozens of ‘magic mushroom’ isolates and cultivars, with the goal to learn more about how their domestication and cultivation has changed them. The findings may point the way to the production of intriguing new cultivars, say the researchers.
- Researchers have developed a new technique called MAbID. This allows them to simultaneously study different mechanisms of gene regulation, which plays a major role in development and disease. MAbID offers new insights into how these mechanisms work together or against each other.
- Paleontologists are getting a glimpse at life over a billion years in the past based on chemical traces in ancient rocks and the genetics of living animals. New research combines geology and genetics, showing how changes in the early Earth prompted a shift in how animals eat.
- And more!
Overview
Genetic technology is defined as the term which includes a range of activities concerned with the understanding of gene expression, advantages of natural genetic variation, modifying genes and transferring genes to new hosts. Genes are found in all living organisms and are transferred from one generation to the next. Gene technology encompasses several techniques including marker-assisted breeding, RNAi and genetic modification. Only some gene technologies produce genetically modified organisms.
Modern genetic technologies like genome editing would not be possible without all the previous generations of genetic technologies that have enabled scientists to discover what genes are, what they do and how DNA can be modified to add, remove or replace genes. You can find major genetic technologies development milestones via the link.
Gene Technology Market
- The valuation of the genetic engineering market is projected to escalate to USD 6.90 MN by the end of 2027.
- Global Genetic Engineering Market is projected to grow at 12.48% CAGR during the assessment period (2017–2027).
- North America holds the largest share in the global genetic engineering market, followed by Europe and the Asia Pacific, respectively.
- Another research provider, MarketsandMarkets, forecasts the genome editing, genome engineering market to grow from USD 3.19 billion in 2017 to USD 6.28 billion by 2022, at a compounded annual growth rate (CAGR) of 14.5% during the forecast period. The key factors propelling market growth are rising government funding and growth in the number of genomics projects, high prevalence of infectious diseases (like COVID-19) and cancer, technological advancements, increasing production of genetically modified (GM) crops, and growing application areas of genomics.
Latest News & Research
Generation of de novo miRNAs from template switching during DNA replication
by Heli A. M. Mönttinen, Mikko J. Frilander, Ari Löytynoja in Proceedings of the National Academy of Sciences
The complexity of living organisms is encoded within their genes, but where do these genes come from? Researchers at the University of Helsinki resolved outstanding questions around the origin of small regulatory genes, and described a mechanism that creates their DNA palindromes. Under suitable circumstances, these palindromes evolve into microRNA genes.
The human genome contains ca. 20,000 genes that are used for the construction of proteins. Actions of these classical genes are coordinated by thousands of regulatory genes, the smallest of which encode microRNA molecules that are 22 base pairs in length. While the number of genes remains relatively constant, occasionally new genes emerge during evolution. Similar to the genesis of biological life, the origin of new genes has continued to fascinate scientists.
All RNA molecules require palindromic runs of bases that lock the molecule into its functional conformation. Importantly, the chances of random base mutations gradually forming such palindromic runs are extremely small, even for the simple microRNA genes. Hence, the origin of these palindromic sequences has puzzled researchers.
Experts at the Institute of Biotechnology, University of Helsinki, Finland resolved this mystery, describing a mechanism that can instantaneously generate complete DNA palindromes and thus create new microRNA genes from previously noncoding DNA sequences. In a project researchers studied errors in DNA replication. Ari Löytynoja, the project leader, compares DNA replication to typing of text.
“DNA is copied one base at a time, and typically mutations are erroneous single bases, like mis-punches on a laptop keyboard. We studied a mechanism creating larger errors, like copy-pasting text from another context. We were especially interested in cases that copied the text backwards so that it creates a palindrome.”
Researchers recognised that DNA replication errors could sometimes be beneficial. They described these findings to Mikko Frilander, an expert in RNA biology. He immediately saw the connection to the structure of RNA molecules.
“In an RNA molecule, the bases of adjacent palindromes can pair and form structures resembling a hairpin. Such structures are crucial for the function of the RNA molecules,” he explains.
Researchers decided to focus on microRNA genes due to their simple structure: the genes are very short — just a few tens of bases — and they have to fold into a hairpin structure to function correctly. A central insight was to model the gene history using a custom computer algorithm. According to postdoctoral researcher Heli Mönttinen, this enables the closest inspection of the origin of genes thus far.
“The whole genome of tens of primates and mammals is known. A comparison of their genomes reveals which species have the microRNA palindrome pair, and which lack it. With a detailed modelling of the history, we could see that whole palindromes are created by single mutation events,” says Mönttinen.
By focusing on humans and other primates, researchers in Helsinki demonstrated that the newly found mechanism can explain at least a quarter of the novel microRNA genes. As similar cases were found in other evolutionary lineages, the origin mechanism appears universal. In principle, the rise of microRNA genes is so easy that novel genes could affect human health. Heli Mönttinen sees the significance of the work more broadly, for example in understanding the basic principles of biological life.
“The emergence of new genes from nothing has fascinated researchers. We now have an elegant model for the evolution of RNA genes,” she highlights.
Although the results are based on small regulatory genes, researchers believe that the findings can be generalised to other RNA genes and molecules. For example, by using the raw materials generated by the newly found mechanism, natural selection may create much more complex RNA structures and functions.
A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing
by Mohindar M. Karunakaran, Hariharan Subramanian, Yiming Jin, Fiyaz Mohammed, Brigitte Kimmel, Claudia Juraske, Lisa Starick, Anna Nöhren, Nora Länder, Carrie R. Willcox, Rohit Singh, Wolfgang W. Schamel, Viacheslav O. Nikolaev, Volker Kunzmann, Andrew J. Wiemer, Benjamin E. Willcox, Thomas Herrmann in Nature Communications
As complicated as their name is, they are important for the human organism in the fight against pathogens and cancer: Vγ9Vδ2 T cells are part of the immune system and, as a subgroup of white blood cells, fight tumor cells and cells infected with pathogens. They recognize their potential victims by their altered cell metabolism.
Research teams from the University of Würzburg and the University Hospital of Würzburg, together with groups in Hamburg, Freiburg, Great Britain and the USA, have now gained new insights into how these cells manage to look inside the cell. Thomas Herrmann, Professor of Immunogenetics at the Institute of Virology and Immunobiology and his colleague Dr. Mohindar Karunakaran at Julius-Maximilians-Universität Würzburg (JMU), were responsible for the study.
“Around one to five percent of lymphocytes, a subgroup of white blood cells in the human body, are so-called Vγ9Vδ2 T cells. However, these multiply massively under certain circumstances,” says Thomas Herrmann, explaining the background to the research project.
“Certain circumstances” in this case means that the T cells encounter so-called phosphoantigens, metabolic products of pathogens, which can also accumulate spontaneously in tumor cells or after drug-based cancer therapy. “Vγ9Vδ2 T cells are therefore crucial for the control of infections and tumors,” explains Herrmann.
As the scientists discovered, phosphoantigens bind to a special group of molecules inside the cell, the so-called BTN3A1 molecules, with which they then form molecular complexes.
“These complexes are recognized by receptors on the surface of the Vγ9Vδ2 T cells, which gives the cell the signal to kill,” says the immunogeneticist.
However, it turned out that relatives of the BTN3A1 molecules that do not bind phosphoantigens are also required to trigger these signals. Which areas of the molecules involved react with each other and which areas are not necessary for this: The research groups have now identified further details on this.
“These findings can improve the clinical use of Vγ9Vδ2 T cells in the fight against tumors,” explains Herrmann.
On this basis, it is conceivable, for example, to develop drugs that strengthen this interaction. However, further analyses of the interaction between the BTN molecules and the receptors of the Vγ9Vδ2 T cells are still required.
However, the BTN molecules are also interesting from another point of view: “Some forms of the BTN3 molecules prevent human cells from becoming infected with the bird flu virus, for example,” says Herrmann. And the BTN3A1 molecule suppresses the fight against tumors by so-called conventional T lymphocytes.
In future studies, the scientists therefore now want to investigate whether these different functions are mediated by the same areas of the BTN molecules and whether certain properties of these molecules can be specifically enhanced or suppressed.
Dual function of Zika virus NS2B-NS3 protease
by Sergey A. Shiryaev, Piotr Cieplak, Anton Cheltsov, Robert C. Liddington, Alexey V. Terskikh in PLOS Pathogens
Viruses have limited genetic material — and few proteins — so all the pieces must work extra hard. Zika is a great example; the virus only produces 10 proteins. Now, in a study, researchers at Sanford Burnham Prebys have shown how the virus does so much with so little and may have identified a therapeutic vulnerability.
In the study, the research team showed that Zika’s enzyme — NS2B-NS3 — is a multipurpose tool with two essential functions: breaking up proteins (a protease) and dividing its own double-stranded RNA into single strands (a helicase).
“We found that Zika’s enzyme complex changes function based on how it’s shaped,” says Alexey Terskikh, Ph.D., associate professor at Sanford Burnham Prebys and senior author of the paper. “When in the closed conformation, it acts as a classic protease. But then it cycles between open and super-open conformations, which allows it to grab and then release a single strand of RNA — and these functions are essential for viral replication.”
Zika is an RNA virus that’s part of a family of deadly pathogens called flaviviruses, which include West Nile, dengue fever, yellow fever, Japanese encephalitis and others. The virus is transmitted by mosquitoes and infects uterine and placental cells (among other cell types), making it particularly dangerous for pregnant women.
Once inside host cells, the virus re-engineers them to produce more Zika. Understanding Zika on the molecular level could have an enormous payoff: a therapeutic target. It would be difficult to create safe drugs that target the domains of the enzyme needed for protease or helicase functions, as human cells have many similar molecules. However, a drug that blocks Zika’s conformational changes could be effective. If the complex can’t shape-shift, it can’t perform its critical functions, and no new Zika particles would be produced.
Researchers have long known that Zika’s essential enzyme was composed of two units: NS2B-NS3pro and NS3hel. NS2B-NS3pro carries out protease functions, cutting long polypeptides into Zika proteins. However, NS2B-NS3pro’s abilities to bind single-stranded RNA and help separate the double-stranded RNA during viral replication were only recently discovered.
In this study, the researchers leaned on recent crystal structures and used protein biochemistry, fluorescence polarization and computer modeling to dissect NS2B-NS3pro’s life cycle. NS3pro is connected to NS3hel (the helicase) by a short amino acid linker and becomes active when the complex is in its closed conformation, like a closed accordion. The RNA binding happens when the complex is open, whereas the complex must transition through the super-open conformation to release RNA. These conformational changes are driven by the dynamics of NS3hel activity, which extends the linker and eventually “yanks” the NS3pro to release RNA.
NS3pro is anchored to the inside of the host cell’s endoplasmic reticulum (ER) — a key organelle that helps shepherd cellular proteins to their appropriate destinations — via NS2B and, while in the closed conformation, cuts up the Zika polypeptide, helping generate all viral proteins. On the other side of the linker, NS3hel separates Zika’s double-stranded RNA and conveniently hands a strand over to NS3pro, which has positively charged “forks” to grab on to the negatively charged RNA.
“There’s a very nice groove of positive charges,” says Terskikh. “So, RNA just naturally follows that groove. Then the complex shifts to the closed conformation and releases the RNA.”
As NS3hel reaches forward to grab the double-stranded RNA, it pulls the complex with it; however, since the NS3pro is anchored in the ER membrane, and the linker can only extend so far, the complex snaps into the super-open conformation and releases RNA. The complex then relaxes back to the open conformation, ready for a new cycle. Meanwhile, when NS3pro detects a viral polypeptide to cut, it forces the complex into the closed conformation, becoming a protease.
The authors call this process “reverse inchworm,” because grabbing and releasing the single-stranded RNA resembles inchworm movements, but backward, with the jaws (the protease) trailing behind. In addition to providing a possible therapeutic target for Zika, this detailed understanding could be applied to other flaviviruses, which share similar molecular machinery.
“Versions of the NS2B-NS3pro complex are found throughout the flaviviruses,” says Terskikh. “It could potentially constitute a whole new class of drug targets for multiple viruses.”
T cell migration requires ion and water influx to regulate actin polymerization
by Leonard L. de Boer, Lesley Vanes, Serena Melgrati, Joshua Biggs O’May, Darryl Hayward, Paul C. Driscoll, Jason Day, Alexander Griffiths, Renata Magueta, Alexander Morrell, James I. MacRae, Robert Köchl, Victor L. J. Tybulewicz in Nature Communications
Researchers at the Francis Crick Institute, working with Imperial College London, King’s College London and University of Cambridge, have shown that an influx of water and ions into immune cells allows them to migrate to where they’re needed in the body.
Our bodies respond to illness by sending out chemical signals called chemokines, which tell immune cells called T cells where to go to fight the infection. This process had already been associated with a protein called WNK1, which activates channels on the cell surface, allowing ions (salts like sodium or potassium) to move into cells.
Until now, it was not clear why ion influx was needed for T cells to move. Through a study, the researchers imaged mouse T cells and observed that, following a chemokine signal, WNK1 is activated at the front of the cells, called the ‘leading edge’. The team showed that the activation of WNK1 opens channels on the leading edge, resulting in an influx of water and ions. They propose that this flow of water causes the cells to swell on the front side, creating space for the ‘actin cytoskeleton’ — the scaffolding inside the cell which holds its structure — to grow into. This propels the whole cell forwards and the process repeats again.
The researchers used gene editing to stop mice producing WNK1, or an inhibitor to prevent WNK1’s activity, observing that the T cells in these mice slowed down or stopped moving completely. Importantly, they found that they could make up for the loss of WNK1 and make the cells speed up by dropping them into a watery solution, which causes the cells to take up water and swell. This shows that the uptake of water, controlled by the WNK1 protein is key for the cells to migrate. The researchers believe that the mechanism they’ve discovered could be involved in lots of different cell types beyond immune cells.
Victor Tybulewicz, Group Leader of the Immune Cell Biology Laboratory & Down Syndrome Laboratory at the Crick, said: “Through this research, we’ve unravelled one of the mysteries of T cell movement, showing that WKN1 causes water and ions to flow into T cells, giving them the space to grow their scaffolding and move forward. Although we looked at T cells, it’s likely that this process is happening in many of our cells and even in diseases like cancer, which is important as when cancer cells spread, it is harder to treat.”
Leon de Boer, former postdoctoral researcher at the Crick and now at the Karolinska Institute in Sweden, said: “This process has been speculated about for decades, but advances in technology have finally allowed us to show how WNK1 helps T cells migrate around the body — water comes in almost like a jet engine moving the cell forward. I am excited that researchers are starting to investigate WNK1 inhibitors to treat diseases like cancer. In my new project, I’m looking at how properties of membranes help cancer cells to move around the body.”
Electric organ discharge from electric eel facilitates DNA transformation into teleost larvae in laboratory conditions
by Shintaro Sakaki, Reo Ito, Hideki Abe, Masato Kinoshita, Eiichi Hondo, Atsuo Iida in PeerJ
The electric eel is the biggest power-making creature on Earth. It can release up to 860 volts, which is enough to run a machine. In a recent study, a research group from Nagoya University in Japan found electric eels can release enough electricity to genetically modify small fish larvae.
The researchers’ findings add to what we know about electroporation, a gene delivery technique. Electroporation uses an electric field to create temporary pores in the cell membrane. This lets molecules, like DNA or proteins, enter the target cell. The research group was led by Professor Eiichi Hondo and Assistant Professor Atsuo Iida from Nagoya University. They thought that if electricity flows in a river, it might affect the cells of nearby organisms.
Cells can incorporate DNA fragments in water, known as environmental DNA. To test this, they exposed the young fish in their laboratory to a DNA solution with a marker that glowed in the light to see if the zebrafish had taken the DNA. Then, they introduced an electric eel and prompted it to bite a feeder to discharge electricity. According to Iida, electroporation is commonly viewed as a process only found in the laboratory, but he was not convinced.
“I thought electroporation might happen in nature,” he said. “I realized that electric eels in the Amazon River could well act as a power source, organisms living in the surrounding area could act as recipient cells, and environmental DNA fragments released into the water would become foreign genes, causing genetic recombination in the surrounding organisms because of electric discharge.”
The researchers discovered that 5% of the larvae had markers showing gene transfer.
“This indicates that the discharge from the electric eel promoted gene transfer to the cells, even though eels have different shapes of pulse and unstable voltage compared to machines usually used in electroporation,” said Iida.
“Electric eels and other organisms that generate electricity could affect genetic modification in nature..”
Other studies have observed a similar phenomenon occurring with naturally occurring fields, such as lightning, affecting nematodes and soil bacteria. Iida is very excited about the possibilities of electric field research in living organisms. He believes these effects are beyond what conventional wisdom can understand. He said, “I believe that attempts to discover new biological phenomena based on such “unexpected” and “outside-the-box” ideas will enlighten the world about the complexities of living organisms and trigger breakthroughs in the future.”
Bimodular architecture of bacterial effector SAP05 that drives ubiquitin-independent targeted protein degradation
by Qun Liu, Abbas Maqbool, Federico G. Mirkin, Yeshveer Singh, Clare E. M. Stevenson, David M. Lawson, Sophien Kamoun, Weijie Huang, Saskia A. Hogenhout in Proceedings of the National Academy of Sciences
Researchers have uncovered the intricate molecular mechanism used by parasitic phytoplasma bacteria, known for inducing ‘zombie-like’ effects in plants. This detailed revelation opens new horizons for groundbreaking applications in biotechnology and even in biomedicine.
The team led by Professor Saskia Hogenhout at the John Innes Centre, in partnership with The Sainsbury Laboratory, has employed X-ray crystallography to unveil the structure and functional mechanism of SAP05. This molecule plays a crucial role in bridging two distinct components inside plant cells.
The discovery sheds new light on a peculiar phenomenon in nature — mostly seen in “witches’ brooms” in which plant stems and leaves proliferate due to Phytoplasma bacteria. This insect-transmitted bacteria triggers diseases like Aster Yellows, significantly diminishing yields in leaf crops including oilseed rape, lettuce, carrots, grapevines, onions, and a variety of ornamental and vegetable crops worldwide.
Previous research by the Hogenhout group revealed how the bacterial protein SAP05 is able to manipulate plants by hijacking molecular machinery called the proteasome. The proteasome breaks down and recycles proteins that are no longer required inside plant cells. SAP05 hijacks this process, causing proteins which regulate growth and development to be dispensed into a molecular recycling centre known as the 26S proteasome. This latest research focusses on how this happens at the structural level.
SAP05 effectively disrupts the molecular recycling pathway, serving as a scaffold that connects its two cellular targets: a transcription factor and the proteasome. Fascinatingly, SAP05 binds in a manner that enables it to ‘lift the dustbin lid’, selectively disposing of developmental proteins, while strategically preserving functions vital for the survival of its plant host.
Professor Hogenhout, group leader at the John Innes Centre, and lead of the research team behind these findings explains: “We now know the structure of this complex and how the protein binds to two cellular components to create a short circuit. Whilst SAP05 allows itself to get involved in the plant, it does not disrupt other important processes. It is so amazing to see evolution crystalized in this way.”
Usually in plants, in fact across all multicellular organisms, this recycling of proteins in the proteasome is dependent on a molecule called ubiquitin. By short-circuiting this process SAP05 provides a new way of carrying out the essential task of protein degradation which serves its own parasitic purpose and is completely independent of ubiquitin. The discovery presents some intriguing possibilities. The researchers were struck by the sophisticated ingenuity of SAP05, a master manipulator, and its promising applications in biotechnology.
First author of the paper Dr Qun Liu said: “It was so exciting to see that this molecule SAP05 had two sides, one side binding to the transcription factor and the other binding to the 26S proteasome, It’s very smart.”
By understanding how this bacterial mechanism interacts with cells at a structural level, the researchers can now use this knowledge to engineer SAP05-like molecules which could be repurposed to remove unwanted proteins such as pathogen effectors or viruses, with an impact on therapeutics, research and in agriculture.
Barley Nodulin 26-like intrinsic protein permeates water, metalloids, saccharides, and ion pairs due to structural plasticity and diversification
by Akshayaa Venkataraghavan, Julian G. Schwerdt, Stephen D. Tyerman, Maria Hrmova in Journal of Biological Chemistry
Aquaporins, which move water through membranes of plant cells, were not thought to be able to permeate sugar molecules, but University of Adelaide researchers have observed sucrose transport in plant aquaporins for the first time, challenging this theory.
The finding, made by researchers from the School of Agriculture, Food and Wine, widens the concept of aquaporins’ role in plant biology and will have implications for the bioengineering of plants for food production and plant survival.
Aquaporins, which belong to a class of membrane proteins known as water-transporters, were first identified in 1993 by American molecular biologist and Nobel Laureate, Peter Agre. The concept of water-permeation in small molecules was accepted at the time, but it was unclear if aquaporins could permeate larger molecules, such as sucrose. This has now been demonstrated, with researchers employing a multidisciplinary approach to observe the biochemical process in HvNIP2;1, which is a Nodulin 26-like Intrinsic Protein found in barley.
“We used nanobiotechnology, electrophysiology, protein chemistry, protein modelling and computational chemistry. We also integrated vast experimental and theoretical data with phylogenomics exploring around 3,000 aquaporins,” said the University of Adelaide’s Professor Maria Hrmova.
HvNIP2;1 is different from other sub-clades of aquaporins in that it has altered structural characteristics and thus it acquired the ability to transport saccharides. Researchers are interested to see what other functions it may serve and how this relates to in planta function.
“We also performed full-scale steered molecular dynamics simulations of HvNIP2;1 and a spinach aquaporin — a structurally and functionally divergent aquaporin compared to HvNIP2;1 — revealing potential rectification of water, boric acid, and sucrose. This will be the subject of future studies,” said Professor Hrmova.
“This work exemplifies that we need to be more open-minded about what different aquaporins may permeate, besides water,” said the paper’s co-author, Professor Steve Tyerman, who previously revealed ion permeation in plant aquaporins.
“Water may be secondary to other important molecules in aquaporins, or some may be co-transport water and other molecules by virtue of a vast array of protein-ligand interactions,” said Professor Hrmova.
Understanding the properties of aquaporins is important for bioengineering to design novel proteins with improved characteristics, such as substrate specificity, thermostability, and folding. These properties are fundamental to the survival of plants as they mediate water and nutrient uptake, govern the distribution of solutes through plants, remove toxins from the cytosol, and recycle valuable sugars.
Given their gatekeeping functions, aquaporins and other membrane transporters are attractive targets in agricultural biotechnology for increasing nutrient contents in edible parts of crop plants, excluding toxic elements, which together directly affect crop quality and ultimately sustained production of our food.
Domestication through clandestine cultivation constrained genetic diversity in magic mushrooms relative to naturalized populations
by Alistair R. McTaggart, Stephen McLaughlin, Jason C. Slot, Kevin McKernan, Chris Appleyard, Tia L. Bartlett, Matthew Weinert, Caine Barlow, Leon N. Warne, Louise S. Shuey, André Drenth, Timothy Y. James in Current Biology
Scientists have amassed genome data for dozens of “magic mushroom” isolates and cultivars, with the goal to learn more about how their domestication and cultivation has changed them. The findings may point the way to the production of intriguing new cultivars, say the researchers.
The study shows that commercial cultivars of the mushroom Psilocybe cubensis lack genetic diversity because of their domestication for human use. Meanwhile, a naturalized population of mushrooms in Australia has maintained much more diversity, they show, including unique gene variants controlling the production of the mushroom’s active ingredient, psilocybin.
“What was surprising was the extreme homozygosity of some cultivars of magic mushroom,” says Alistair McTaggart of The University of Queensland, Australia. “Some of these cultivars have been nearly stripped of any diversity except at their genes controlling sexual reproduction.”
“Whether this happened intentionally, by targeted inbreeding to fix traits over the last half century, or unintentionally through a lack of diversity to cross against is hard to know,” he says. “The trailblazers who domesticated magic mushrooms have set the stage for how we can advance cultivation and innovate with shrooms as we improve our understanding of psilocybin and its benefits.”
McTaggart says that research into these mushrooms has been driven by an underground community of people interested in magic mushrooms, many of whom are co-authors on the new study. With no financial support for the effort, the wider community of people interested in magic mushrooms collected the cultivars and isolates under study, sending samples at their own expense and risk.
Ultimately, the researchers sequenced and assembled DNA data for more than 100 varieties of magic mushrooms. As part of the study, the team sequenced genomes from 38 isolates from Australia and compared them to 86 commercially available cultivars. They wanted to find out whether the mushrooms were introduced to Australia and how domestication has changed those that are commercially available.
Their analyses showed that the Australian mushrooms are naturalized, having bounced back to a population size large enough to maintain genetic diversity after their initial introduction to the country. By comparison, commercial cultivars are sorely lacking in diversity across their genomes. The findings suggest that some of the unique gene variants in Australia may allow for differences in the synthesis of psilocybin and related compounds. The data they’ve generated on mating compatibility and diversity at the genes controlling production of psilocybin “will advance breeding for ‘designer shrooms,’ in which heterozygosity of psilocybin alleles may unlock variety in the production of psychedelic tryptamines,” McTaggart says.
In fact, he reports, their start-up company, Funky Fungus, has already started to translate the findings for developing designer cultivars. McTaggart says these developments may have significance for the use of psilocybin as a natural compound, with potential benefits for treating mental health disorders.
“Magic mushrooms are the cheapest source of psilocybin and may fill a niche in natural drug development,” he said. “There is yet more to understand about how magic mushrooms produce other compounds that may impact a psilocybin experience, and this will be an exciting area of research to watch unfold.”
Combinatorial single-cell profiling of major chromatin types with MAbID
by Silke J. A. Lochs, Robin H. van der Weide, Kim L. de Luca, Tessy Korthout, Ramada E. van Beek, Hiroshi Kimura, Jop Kind in Nature Methods
Researchers from the group of Jop Kind developed a new technique called MAbID. This allows them to simultaneously study different mechanisms of gene regulation, which plays a major role in development and disease. MAbID offers new insights into how these mechanisms work together or against each other.
DNA is the most important carrier of genetic information. Each cell contains approximately two meters of DNA. To ensure that all this genetic material fits into the small cell nucleus, it must be tightly packed. The DNA is therefore wrapped around a special type of protein, a histone. The packages of DNA and histones are called chromatin.
Chromatin not only ensures that all the DNA fits into the cell, it also determines which parts of the genetic material can be read by the cell. For example, a piece of DNA that is tightly wrapped around the histone is more difficult to read than a piece of DNA that is packed more loosely. Ultimately, the way in which chromatin is folded determines which parts of the genetic material are expressed and which parts are not. This pattern of gene expression differs per cell type. Different genes are active in a skin cell than in a liver cell, for example.
The activity of genes is not always the same: a different pattern of genes may be active in one moment compared to another. That is because the structure of chromatin can change. For instance, changes can occur in the histones, which are called histone modifications. Certain proteins can also bind to the chromatin. Both processes influence the readability of the DNA and therefore the gene expression.
In recent years, various technologies have been developed to investigate the mechanisms of gene regulation. However, there was still a technique missing to allow researchers to simultaneously look at multiple mechanisms in one cell. The group of Jop Kind therefore designed a new technique: MAbID. With MAbID, researchers can simultaneously study multiple types of histone modifications and the proteins that bind to chromatin.
“With our new technique, we can see how the different mechanisms of gene expression are connected, for example how they work together or against each other. And the great thing is that we no longer need separate experiments for this, we can study everything at once in each individual cell. That makes the research much more efficient,” Silke Lochs, one of the researchers on the project, explains.
Common origin of sterol biosynthesis points to a feeding strategy shift in Neoproterozoic animals
by T. Brunoir, C. Mulligan, A. Sistiaga, K. M. Vuu, P. M. Shih, S. S. O’Reilly, R. E. Summons, D. A. Gold in Nature Communications
Paleontologists are getting a glimpse at life over a billion years in the past based on chemical traces in ancient rocks and the genetics of living animals. Research combines geology and genetics, showing how changes in the early Earth prompted a shift in how animals eat.
David Gold, associate professor in the Department of Earth and Planetary Sciences at the University of California, Davis, works in the new field of molecular paleontology, using the tools of both geology and biology to study the evolution of life. With new technology, it’s possible to recover chemical traces of life from ancient rocks, where animal fossils are scarce.
Lipids in particular can survive in rocks for hundreds of millions of years. Traces of sterol lipids, which come from cell membranes, have been found in rocks up to 1.6 billion years old. In the present day, most animals use cholesterol — sterols with 27 carbon atoms (C27) — in their cell membranes. In contrast, fungi typically use C28 sterols, while plants and green algae produce C29 sterols.
The C28 and C29 sterols are also known as phytosterols. C27 sterols have been found in rocks 850 million years old, while C28 and C29 traces appear about 200 million years later. This is thought to reflect the increasing diversity of life at this time and the evolution of the first fungi and green algae. Without actual fossils, it’s hard to say much about the animals or plants these sterols came from. But a genetic analysis by Gold and colleagues is shedding some light.
Most animals are not able to make phytosterols themselves, but they can obtain them by eating plants or fungi. Recently, it was discovered that annelids (segmented worms, a group that includes the common earthworm) have a gene called smt, which is required to make longer-chain sterols. By looking at smt genes from different animals, Gold and colleagues created a family tree for smt first within the annelids, then across animal life in general. They found that the gene originated very far back in the evolution of the first animals, and then went through rapid changes around the same time that phytosterols appeared in the rock record. Subsequently, most lineages of animals lost the smt gene.
“Our interpretation is that these phytosterol molecular fossils record the rise of algae in ancient oceans, and that animals abandoned phytosterol production when they could easily obtain it from this increasingly abundant food source,” Gold said. “If we’re right, then the history of the smt gene chronicles a change in animal feeding strategies early in their evolution.”
Subscribe to Paradigm!
Medium. Twitter. Telegram. Telegram Chat. Reddit. LinkedIn.
Main Sources
Research articles
