Genetics biweekly vol.41, 2nd November — 16th November
TL;DR
- Researchers have discovered that the affinity between cells can control complex developmental processes.
- A new genetic study finds large dams restrict platypus movement, with significant implications for their conservation.
- Researchers have compiled the first genome sequences of desert pupfish from the American Southwest, including the unique Devils Hole pupfish. The genomes of the 8 Devils Hole pupfish sequenced contained an amazing number of identical stretches of DNA, amounting to 58% of the genome — among the most inbred of any known vertebrate. Paradoxically, of 15 gene deletions, five involved adaptation to hypoxia, or low oxygen levels, which are characteristic of the pupfish’s habitat.
- A research team have discovered a mechanism of flowering plant sperm compaction and gathered clues as to why it is required.
- Researchers have published seven draft genomes for Nordic hare species.
- Biologists demonstrate how the auxiliary factor CGL160 contributes to the synthesis of crucial parts of the photosynthetic machinery.
- The formation of fruiting bodies for sexual reproduction is a central developmental process in fungi. Even though genetic methods have been applied in recent decades to identify a large number of factors involved in this process, we still lack an understanding of how the formation of different cell types is regulated. A research team has gained new insights by studying a mutant sac fungus that is infertile. The mutant is impaired in its respiratory chain, thus lacking the energy to form fruiting bodies.
- Researchers have developed a three-dimensional model that shows how exposure to cadmium might lead to congenital heart disease. Affecting nearly 40,000 newborns a year, congenital heart disease is the most common type of birth defect in the United States.
- Researchers identify a gene that enables beta cells to communicate with each other, helping the pancreas to respond to glucose by insulin secretion.
- More adaptable crops are needed to address global hunger and worsening challenges in food production. Researchers have now developed new genetic blueprints for two types of groundcherry. Their work can help unlock the potential for orphan crops like groundcherry to strengthen global food supplies. It may also help reveal how plants evolve and develop new traits.
- 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
Eya-controlled affinity between cell lineages drives tissue self-organization during Drosophila oogenesis
by Vanessa Weichselberger, Patrick Dondl, Anne-Kathrin Classen in Nature Communications
During the growth and development of living organisms, different types of cells must come into contact with each other in order to form tissues and organs together. A small team working with Prof. Dr. Anne Classen of the Excellence Cluster CIBSS — Centre for Integrative Biological Signalling Studies of the University of Freiburg has discovered that complex changes in form, or morphogenesis, during development are driven exclusively via the affinity of cells to each other. The researchers examined the egg chambers of fruit flies (Drosophila melanogaster) and combined genetic methods and mathematical modeling in their work.
The lead author of the study and a member of Classen’s lab, Dr. Vanessa Weichselberger, summarized the team’s work: “We wanted to find out how different types of cells organize their morphogenesis with each other in order to form functional units.” She continues, “The egg chamber is a good example, because within it, different cell populations must self-organize into functional units.”
The egg chamber is the structure in which an immature egg cell, or oocyte, matures until it is ready for fertilization. Drosophila’s egg chamber looks like a tiny football. Inside, the growing egg cell is located on one side, and on the other are 15 nurse cells that provide nutrients for the immature egg cell. In order to produce an egg, the egg cell must mature, while the nurse cells are ultimately removed.
Both processes — the maturation of the egg cell and the removal of the nurse cells, are dependent on an external layer of epithelial cells. For this purpose, the epithelial cells are divided into specialized groups, which — based on their function — must either make contact with the nurse cells or the egg cell. This partnering between the inner and outer cells is a complex process which takes place while simultaneously the size relationships within the egg chamber continually change.
“Until now, the mechanisms that could robustly control such a dynamic process were unknown,” says Classen.
The researchers observed that the epithelial cells specialized in removal of the nurse cells spread out and flatten over the nurse cells. This creates a particularly large contact area with the nurse cells underneath. Weichselberger explains, “That could be explained by heightened affinity between the two cell types. So we hypothesized that the matching of inner and outer cells took place through simple mechanical processes of attraction and repulsion.” A heightened affinity of one specialized group of epithelial cells to the nurse cells would lead to the rest of the epithelial cells being displaced from the nurse cells onto the egg cell. The researchers found that a protein, Eya, which can control the activity of genes, influences the contact behavior between epithelial cells and nurse cells. If the researchers increased the concentration of Eya in the epithelial cells, these increased their contact surface area with the nurse cells. If they removed Eya, the contact surface was minimized.
In order to test their hypothesis, the developmental biologists used mathematical models. To do this, they worked with Prof. Dr. Patrick Dondl of the Faculty of Mathematics and Physics of the University of Freiburg. Dondl created mathematical models that could simulate different degrees of mechanical affinity between the cells.
“The mathematical models allowed us to show that a change in affinity dependent on Eya levels was sufficient to control the complex process of matching cell types,” explains Weichselberger. “That meant that we could use Eya as a set screw to genetically control partner location,” she says.
By genetically changing the Eya concentrations in the epithelial cells and simulating these experiments on the computer, the researchers were able to test if the Eya-regulated affinity between the epithelial cells and nurse cells is responsible for self-organization. They observed that solely by manipulating Eya, they could deliberately control which epithelial cells spread out on the nurse cells and which epithelial cells came into contact with the egg cell. This showed that Eya — via affinity regulation — is the main regulator of self-organization between the epithelial cells and the inner cells — the nurse cells and the egg cell. The results surprised Classen, who led the study.
She explains, “Specific affinity is actually sufficient as a mechanism for controlling such complex development processes. And in a way that is extremely flexible, robust, and independent from the volume of the egg chamber.”
This mechanism is not limited solely to the egg chamber. The development of sperm cells in Drosophila males is also dependent on Eya. Here, too, the protein Eya controls the affinity between the developing, interior sperm cells and the exterior epithelial cells. It is unclear if these results can also be applied to other animals or humans. But comparable structures and developmental processes during oogenesis in other species make this seem possible.
Mountain- and brown hare genetic polymorphisms to survey local adaptations and conservation status of the heath hare (Lepus timidus sylvaticus, Nilsson 1831)
by Craig T. Michell, Jaakko L. O. Pohjoismäki, Göran Spong, Carl-Gustaf Thulin in Scientific Data
Researchers at the University of Eastern Finland, in collaboration with colleagues from the Swedish University of Agricultural Sciences (SLU, Sveriges lantbruksuniversitet), have published seven draft genomes for Nordic hare species.
The genomes include three heath hares (Lepus timidus sylvaticus), a subspecies of the mountain hare (Lepus timidus) that is unique to southern Scandinavia and western Estonia. Instead of a white winter pelage that is typical of boreal/arctic mountain hares (Lepus timidus timidus), the heath hare has a grey/blue winter pelage. It is generally believed that this form of winter coloration is a specific adaptation to the less reliable snow coverage in southern Scandinavia. The distribution of heath hares overlaps with that of the non-native brown hare, which seem to outcompete heath hares wherever they occur. Together with the threat from land use, this competition has pushed the uniquely adapted mountain hare subspecies at risk of going extinct.
Genomic knowledge helps to understand the genetic basis for traits that are important for specific adaptations and provides information about the evolutionary relationships as well as historical origins of the populations. Therefore, the first whole genome sequences from three heath hares were acquired along with two mountain hares, and two brown hares. Rather surprisingly, the genome of the heath hare differed notably from the nominal mountain hares, despite the thousands of years of coexistence, demonstrating that the subspecies difference is not restricted to local adaptation but represents a unique, old evolutionary divergence. This suggests that the heath hare colonized Scandinavia from the south after the most recent ice age, whereas the contemporary mountain hare probably arrived later from the northeast.
The obtained genome sequences are useful also for screening genetic variation that could be used for investigations of genetic differentiation and local adaptations. Hopefully, these sequence data will provide authorities with tools to assess the status of the unique heath hares and help conservation efforts.
Severe inbreeding, increased mutation load and gene loss-of-function in the critically endangered Devils Hole pupfish
by David Tian, Austin H. Patton, Bruce J. Turner, Christopher H. Martin in Proceedings of the Royal Society B: Biological Sciences
As its name implies, the Devil’s Hole pupfish lives in a truly hellish environment.
Confined to a single deep limestone cave in Nevada’s Mojave Desert, 263 of them live in water that hovers around 93 degrees Fahrenheit year-round, with food resources so scarce that they are always on the edge of starvation, and with oxygen levels so low that most other fish would die immediately. The pupfish, Cyprinodon diabolis, live in the smallest habitat of any known vertebrate. New research now documents the extreme effect that these harsh and isolated conditions have had on this fish’s genetic diversity.
In a paper, University of California, Berkeley, biologists report the first complete genome sequences of eight pupfish species from the American Southwest — 30 individuals in all, including eight Devils Hole pupfish. Astoundingly, the Devils Hole pupfish is so inbred that 58% of the genomes of these eight individuals are identical, on average.
“High levels of inbreeding are associated with a higher risk of extinction, and the inbreeding in the Devils Hole pupfish is equal to or more severe than levels reported so far in other isolated natural populations, such as the Isle Royale wolves in Michigan, mountain gorillas in Africa and Indian tigers,” said lead researcher Christopher Martin, UC Berkeley associate professor of integrative biology and curator of ichthyology in the campus’s Museum of Vertebrate Zoology. “Although we were not able to directly measure fitness, the increased inbreeding in these pupfish likely results in a substantial reduction in fitness.”
Other pupfish species are also inbred, the researchers found, but only between 10% and 30% of their genomes are identical.
Graduate student David Tian, lead author of the study, said that the level of inbreeding in the Devils Hole pupfish is equivalent to what would happen if four to five generations of siblings mated with one another. This tends to burn in or fix, rather than weed out, harmful mutations, potentially dooming a population to extinction by mutational meltdown. The Devils Hole pupfish species is currently doing well in the wild and in captive or “refuge” populations, but such low genetic diversity could spell trouble as the climate changes and human impacts become greater.
In the face of these potential threats, the new genome sequences will help scientists and conservationists assess the health of native pupfish populations and potentially intervene in refuge populations to increase the genetic diversity of these species — the Devils Hole pupfish, in particular.
“With this new genomic data, there’s a lot of potential to look not just at genetic diversity and how these species are related to each other phylogenetically, but also look at inbreeding and mutation load to get an idea of what their current status is, how evolutionary history may have influenced their current genetic variation, and think about where the population is going and what we should do, if anything, to preserve these species,” Tian said.
Pupfish species are scattered around the globe and tend to like isolated lakes and springs, often with extreme conditions that most fish would find unsurvivable. About 30 species inhabit warm, salty desert springs and streams in California and Nevada. Martin has studied various pupfish populations, including several on San Salvador Island in the Bahamas, to understand the genetics behind their adaptation to extreme conditions and unusual ecological niches. The Devils Hole pupfish, however, is unique in its small range and perilous existence, Martin said, making its fluctuating population in the wild worrisome to conservationists.
“Part of the question about these declines is whether they may be due to the genetic health of the population,” Martin said. “Maybe the declines are because there are harmful mutations that have become fixed because the population is so small.”
The small population is partly a result of human incursions into their habitat, Martin noted. Local ranchers and developers pumped groundwater in the region in the 1960s and ’70s that drastically reduced the water level in Devils Hole, leading to a drop in population levels. A 1976 Supreme Court ruling that allowed the federal government to limit groundwater pumping saved Devils Hole and the resident population, while captive breeding at a nearby 100,000-gallon pool in the Ash Meadows National Wildlife Refuge rescued the species. Nevertheless, a decline in the 1990s led the wild population to its nadir in 2013: 35 individuals. The wild population has since recovered, while the refuge population has ballooned to about 400, twice the wild population.
Humans are not totally to blame for the lack of genetic diversity in the Devils Hole pupfish, however. The UC Berkeley researchers also sequenced the genome of a pupfish collected in 1980 and held at the University of Michigan. It showed inbreeding and a lack of genetic diversity similar to that found in individuals collected recently, most of which died a natural death. This implies that the pupfish has likely seen population bottlenecks frequently over hundreds, if not thousands, of years.
One result of this, Martin and Tian found, is that 15 genes have disappeared entirely from the Devils Hole pupfish genome. Five of them seem to be involved in adaptation to living in low-oxygen or hypoxic environments.
“These deletions are a paradox, because this is a habitat where you’re most exposed to hypoxia,” Martin said. “It could have something to do with the stability of the habitat over time. But it looks to us like the hypoxia pathway is broken. Once you break one gene, it doesn’t really matter if you break additional genes in that regulatory pathway. Our future work is to actually look at what these deletions do. Do they increase tolerance of hypoxia? Do they decrease tolerance of hypoxia? I think those two scenarios are equally plausible at this time.”
Selective breeding within a captive population of Devils Hole pupfish could help increase the diversity and perhaps save the species from eventual extinction, he said. And to restore genes already lost, CRISPR genome editing could add them back. The fact that the genome of the fish collected in 1980 was about as inbred as today’s fish is “maybe good news,” Martin said, “in that the population has historically been highly inbred with very low genetic diversity, suggesting that the recent decline in the ’90s, with population bottlenecks to only 35 fish in 2013 and 38 fish in 2007, doesn’t seem to have had much of an effect.”
Tian is currently analyzing about 150 complete genome sequences of nine species of American pupfish to get a more complete picture of the deleterious mutations and gene deletions in the various Southwestern populations. He sees the study as an example of what conservation genomics can do for endangered and possibly inbred populations around the world.
“We’re on a really cool cusp when it comes to using genomic data and applying it to conservation, especially at a time where it’s a problem that is likely only going to get worse with climate change and increased habitat fragmentation and just anthropogenic changes,” he said.
Tian is leery of genetic interventions, however, since little is known about how genes influence the physical and behavioral characteristics of a species and how this relates to fitness and adaptation to a specific environment. Conservation should still be a priority.
“The answer is still increased funding for these populations, protecting habitats, legal avenues for protecting these species and figuring out ways for humans and these endangered species to coexist on this planet,” he said.
Histone H2B.8 compacts flowering plant sperm through chromatin phase separation
by Toby Buttress, Shengbo He, Liang Wang, Shaoli Zhou, Gerhard Saalbach, Martin Vickers, Guohong Li, Pilong Li, Xiaoqi Feng in Nature
Sperm cells have compact bundles of DNA, yet exactly how and why sperm cell nuclei are condensed in flowering plants has been a mystery, until now.
A research team from the John Innes Centre have discovered a mechanism of flowering plant sperm compaction and gathered clues as to why it is required.
How do flowering plants compact their DNA in sperm cells?
Researchers from the Professor Xiaoqi Feng group have shown how in flowering plants, sperm chromatin, a complex of DNA and proteins, is compacted by a special histone protein that spontaneously self-aggregates as oil droplets do in water, a phenomenon known as phase separation.
Flowering plants use a different mechanism to animals and non-seed plants (such as ferns and mosses). In these other organisms, sperm chromatin undergoes near-complete replacement of histones with protamines which highly compacts the DNA. The mechanism of compaction in flowering plants was unknown, as they do not have protamines but instead maintain histone-based chromatin.
Professor Feng’s research team used super-resolution microscopy, comparative proteomics, single-cell-type epigenomic sequencing and 3D genome mapping to investigate this mystery. The team examined Arabidopsis thaliana sperm, vegetative and leaf cell nuclei using super-resolution microscopy, and identified a histone variant H2B.8 that is specifically expressed in sperm nuclei via comparative proteomics.
H2B.8 has a long intrinsically disordered region (IDR), a feature that frequently allows proteins to undergo phase separation. The research found nearly all flowering plant species have H2B.8 homologs (copies), all of which contain an IDR, suggesting important functions.
Using imaging, epigenomic sequencing and 3D genome mapping, the researchers show that H2B.8 condenses sperm DNA by inducing the phase separation and aggregation of euchromatin, the part of chromatin that is comparatively decondensed and transcriptionally active. Because euchromatin takes up most of the nuclear volume its aggregation is a highly effective mechanism for nuclear condensation. They also show that owing to the specific localization of H2B.8 within inactive euchromatin, its condensation function does not adversely affect transcription and the activity of genes.
Why do flowering plants condense their DNA in this way?
Many organisms have highly condensed sperm. For example, mammals produce motile sperm which swims, and they benefit from compact DNA bundles in their sperm nuclei to achieve a small and hydrodynamic sperm head that aids swimming velocity. Flowering plants produce pollen which does not swim, posing the question ‘why does DNA compaction occur in the sperm of flowering plants?’
The research team conclude that H2B.8 mediated sperm condensation is important for male fertility. The researchers speculate that sperm condensation is important for flowering plants, in which sperm cells need to travel through a long pollen tube to reach the egg cell deeply embedded in maternal tissues. Consistent with this idea, gymnosperms, a group of non-flowering seed plants (for example conifers, cycads) that have exposed egg apparatus have uncondensed sperm nuclei and lack H2B.8.
Dr Toby Buttress first author of the study said: “We propose that H2B.8 is a flowering plant evolutionary innovation that achieves a moderate level of nuclear condensation compared to protamines, which sacrifice transcription for super compaction. H2B.8-mediated condensation is sufficient for immotile sperm and compatible with gene activity.”
The team also speculate that such nuclear condensation mechanisms are likely to operate outside of flowering plants, in transcriptionally active cells that favour smaller nuclei.
Dr Buttress continues: “We have discovered the first example of a specific core histone variant being able to affect the phase separation properties of chromatin. “We demonstrate an exciting new mechanism of genome compaction that does not compromise gene activity.”
Fragmentation by major dams and implications for the future viability of platypus populations
by Jose L. Mijangos, Gilad Bino, Tahneal Hawke, Stephen H. Kolomyjec, Richard T. Kingsford, Harvinder Sidhu, Tom Grant, Jenna Day, Kimberly N. Dias, Jaime Gongora, William B. Sherwin in Communications Biology
The platypus is possibly the most irreplaceable mammal existing today. They have a unique combination of characteristics, including egg-laying despite being mammals, venomous spurs in males, electroreception for locating prey, biofluorescent fur, multiple sex chromosomes, and the longest evolutionary history in mammals.
Platypuses are a threatened species in some Australian states and their conservation is of concern more broadly, due to known decline in their populations. A new study examined the genetic makeup of platypuses in free-flowing and nearby rivers with large dams in New South Wales. These included the free-flowing Ovens River, along with the dammed Mitta Mitta River, and the free-flowing Tenterfield Creek, along with the nearby Severn River regulated by a large dam.
The study found that large dams are significant barriers to platypus movements. This was reflected in greater genetic differentiation between platypuses above and below large dams compared to rivers without dams. Importantly, this genetic differentiation increased over time since the dam was built, reflecting the long-term impacts of the dam.
“We extracted the DNA from the blood collected by our Platypus Conservation Initiative researchers at UNSW. By using thousands of molecular markers, we were able to identify a strong signal indicating that genetic differentiation increased rapidly between platypuses below and above these large dams,” said lead author Dr Luis Mijangos, a former UNSW PhD student who is now at the University of Canberra.
Professor Richard Kingsford, Director of the UNSW Centre for Ecosystem Science and one of the paper’s authors, said, “This is a profound result with significant implications for platypus conservation.
“We’ve long suspected that prey can restrict platypus movements, but this is the ‘smoking gun’. These animals just can’t get around big dams.”
This movement restriction of platypuses separated by large dams means there is limited or no gene flow between groups, making these separate populations increasingly vulnerable to threats. There is increased possibility of inbreeding depression, loss of adaptive genetic variation, failure to recolonise areas where local extinctions have occurred, and failure to disperse to areas with more suitable conditions.
“We know that platypuses are declining in many parts of their range in eastern Australia, affected by many threats. This study identifies one of the main threats to this iconic species,” said Dr Gilad Bino, leader of the Platypus Conservation Initiative at UNSW Sydney and another author of the study.
“There is still much we don’t know about the ecology of the platypus, but given its international status as a monotreme, it is increasingly vital that we understand and manage the threats to this unique species.”
The authors recommend that water conservation and management planning should consider alternative approaches to large dams. These could include storing water in off-river reservoirs and implementing strategies to reduce the effects of dams, such as the artificial relocation of individual platypuses between groups above and below dams, or the construction of passage structures that increase dispersal.
CGL160-mediated recruitment of the coupling factor CF1 is required for efficient thylakoid ATP synthase assembly, photosynthesis, and chloroplast development in Arabidopsis
by Bennet Reiter, Lea Rosenhammer, Giada Marino, Stefan Geimer, Dario Leister, Thilo Rühle in The Plant Cell
LMU biologists demonstrate how the auxiliary factor CGL160 contributes to the synthesis of crucial parts of the photosynthetic machinery.
Photosynthesis is the means by which plants, algae, and cyanobacteria extract their ‘food’ in the form of energy-rich biomolecules from sunlight, carbon dioxide, and water. It is a complex process, from which researchers are still coaxing many new details. A team led by LMU biologists Thilo Rühle, Bennet Reiter, and Prof. Dario Leister has now solved another piece of the puzzle of this essential process and elucidated the role of the auxiliary factor CGL160, as the scientists report.
Photosynthesis takes place in several partial reactions at the so-called thylakoid membranes in the chloroplasts, where various pigments absorb the electromagnetic radiation of sunlight. Specific protein complexes in conjunction with ATP synthases then convert this light energy into chemical energy in the form of ATP. This enables the plant, among other things, to synthesize carbohydrates as energy-rich ‘fuel’ for cellular respiration. As ‘molecular machines,’ ATP synthases are therefore a vital component of plant metabolism.
How ATP synthases are assembled in the cell has not yet been fully clarified. Based on the model organism Arabidopsis thaliana, the researchers have now been able to demonstrate that the protein CGL160 plays a key role in the process by recruiting the coupling factor CF1 of the ATP synthase.
“The protein CGL160 sits with its base in the thylakoid membrane, while its N-terminal domain protrudes like a rod and fishes the soluble CF1 portion of the ATP synthases out of the fluid inside the chloroplasts. This portion of the protein binds the CF1 ‘headpiece’ and facilitates linkage with the portion of the ATP synthase embedded in the thylakoid membrane, making its formation considerably more efficient,” explains Thilo Rühle.
Even under unfavorable growth conditions, the presence of auxiliary factors such as CGL160 prove to be advantageous: The LMU biologists discovered that an absence of CGL160, with its CF1-binding function, under conditions of light deficiency negatively impacts the development of chloroplasts.
“We observed that the chloroplast structure of corresponding mutants suffers more during short days with just eight hours of daylight. We advance the hypothesis therefore that the interaction between the N-terminal domain of CGL160 and CF1 is also an evolutionary adaptation that enables plants to cope better in various light conditions,” says Rühle.
The researchers also found clues as to the evolutionary origin of CGL160. In experiments with Arabidopsis thaliana, they succeeded in functionally replacing the membrane domain of CGL160 with the Atp1 protein from cyanobacteria of the genus Synechocystis. “Around 80 percent of the function can be restored in this way. This suggests that CGL160 in land plants may have come from a predecessor protein of cyanobacteria,” says Rühle. Indeed, plant cells acquired their chloroplasts through incorporation and functional integration of cyanobacteria.
This set in train the emergence of a complex synthesis plan for photosynthetic machinery. To better understand this plan, the LMU biologists now want to identify all auxiliary factors — in addition to CGL160 and a handful of other currently known factors — that are important for the assembly and function of ATP synthases in plant thylakoid membranes.
“We assume that there are much fewer factors involved here than in the photosystems themselves — accordingly, ATP synthase is an easier potential route for the regulation of photosynthesis,” says Rühle. “In the future, people could use this knowledge for various applications, such as modifying plants so that they can optimally cover their ATP requirements even when exposed to stressors like heat or extreme light conditions.”
Sordaria macrospora Sterile Mutant pro34 Is Impaired in Respiratory Complex I Assembly
by Andrea Hamann, Heinz D. Osiewacz, Ines Teichert in Journal of Fungi
Sordaria macrospora is a model system for studying the development of fruiting bodies in sac fungi, so-called filamentous ascomycetes. Using conventional mutagenesis, more than 100 developmental mutants were generated for this fungus in the 1990s.
Assistant Professor Dr. Ines Teichert from the General and Molecular Botany group at the Department of Biology and Biotechnology at the Ruhr University Bochum, Germany, in cooperation with Dr. Andrea Hamann and Professor Heinz D. Osiewacz from the Goethe University Frankfurt, has been studying such a mutant: unlike the wild-type strain, the so-called pro34 mutant doesn’t form mature fruiting bodies and sexual spores, and in addition has a slower growth rate. Through genome sequencing, the researchers identified a major gap in a gene, which they named pro34. In the wild-type strain, this gene is affected by RNA editing during fruiting body formation; this means that a new variant of the RNA and protein is generated at this point, which may have a specific function.
But what is the function of PRO34 in the first place? “Using fluorescence microscopy, we successfully localised PRO34 in the mitochondria,” explains Ines Teichert. These cell organelles contain the respiratory chain, a series of protein complexes that, to put it simply, help generate energy in the form of adenosine triphosphate (ATP). In the mutant, one of these complexes is missing. The mutant is nevertheless viable; this is because fungi as well as plants possess various alternative pathways in the mitochondrial respiratory chain to compensate for such defects.
“However, this compensation is insufficient to cover the high energy demand during fruiting body formation, and thus the mutant remains sterile,” says Ines Teichert.
A surprising discovery was that the so-called alternative oxidase (AOX) is likewise activated in the pro34 mutant. “According to previous findings, AOX usually compensates for other defects and must therefore fulfil additional functions,” points out Ines Teichert. The authors speculate about a protective function of AOX against oxidative stress, since a defect in the mitochondrial respiratory chain leads to increased formation of oxygen radicals.
“An explanation could also be that AOX helps in the assembly of certain mitochondrial complexes,” believe the authors. “Consequently, the pro34 mutant is an excellent starting point for subsequent analyses.”
Cardiac Development in the Presence of Cadmium: An in Vitro Study Using Human Embryonic Stem Cells and Cardiac Organoids
by Xian Wu, Yichang Chen, Anthony Luz, Guang Hu, Erik J. Tokar in Environmental Health Perspectives
Researchers have developed a three-dimensional model that shows how exposure to cadmium might lead to congenital heart disease. Affecting nearly 40,000 newborns a year, congenital heart disease is the most common type of birth defect in the United States. The model was created by scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.
Cadmium is a metal that can be released into the environment through mining and various industrial processes, and it has been found in air, soil, water, and tobacco. The metal can enter the food chain when plants absorb it from soil. Previous studies suggested that maternal exposure to cadmium might be a significant risk factor for congenital heart disease.
Using models derived from human cells and tissues, called in vitro models, researchers designed a 3D organoid model that mimics how the human heart develops. The researchers saw how exposure to low levels of cadmium can block usual formation of cardiomyocytes, which are the major type of cells that form the heart. In doing so, they revealed the biological mechanisms that might explain how cadmium could induce heart abnormalities.
“The models we created are useful for not only studying cadmium, but for studying other chemicals and substances as well,” said study lead Erik Tokar, Ph.D., from the Mechanistic Toxicology Branch of the NIEHS Division of Translational Toxicology (DTT).
For the study, the researchers developed three different models to evaluate the effects of cadmium on different stages of heart development.
First, they used human pluripotent stem cells to develop 3D embryoid bodies to mimic early steps in tissue and organ formation in humans. They then used a 2D in vitro model that included a fluorescent regulatory protein system (NKX2–5) known to be involved in heart development, which allowed them to look at cadmium toxicity after exposure.
The 3D cardiac organoid model, which can simulate the beating heart, confirmed what was seen in the other two models, showing how low doses of cadmium can inhibit the cardiomyocytes from functioning properly. The study builds on decades of work by toxicology researchers to advance knowledge about how environmental exposures may contribute to human diseases including cancer, cardiovascular disease, autism, and other conditions.
“These new models are leveraging advances in technology that allow us to model human biology in a way that identifies real human health hazards,” noted Brian Berridge, D.V.M., Ph.D., scientific director, DTT. “They also help reduce our reliance on animal testing.
“We found that early exposure to human-relevant levels of cadmium lead to a dramatic inhibitory effect on cardiomyocyte differentiation, whereas later stage exposures did not have this effect,” said Xian Wu, Ph.D., who conducted these studies. “This cadmium exposure also damaged the cardiac organoid functionality.”
Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function
by Keiichi Katsumoto, Siham Yennek, Chunguang Chen, Luis Fernando Delgadillo Silva, Sofia Traikov, Dror Sever, Ajuna Azad, Jingdong Shan, Seppo Vainio, Nikolay Ninov, Stephan Speier, Anne Grapin-Botton in Nature Communications
Diabetes, which affects millions of people worldwide, develops when the body either generates insufficient amounts of the hormone insulin- a hormone that maintains healthy blood sugar — or when the body cannot effectively use the insulin it produces. When the number of beta cells is too low or they aren’t functioning properly, there isn’t enough insulin getting released. Beta cells communicate with each other to secrete insulin in a coordinated manner. An international team of scientists from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, the Paul Langerhans Institute Dresden (PLID), and the Universities of Oulu, Finland and Copenhagen, Denmark now shows that the gene Wnt4 in beta cells enables them to sense glucose and release the hormone insulin that enables other cells in the body to store glucose. These insights could help to create replacement beta cells for diabetes therapy in the future.
At birth, a baby starts to eat food and turns it into energy. Many nutrients can be converted to sugar (glucose) and be released into the bloodstream. Higher blood sugar levels signal the beta cells in the pancreas to release insulin, which lets the blood sugar into the cells to use or store it as energy. However, at different stages of life, the food-sensing beta cells need to adapt to different foods and needs. In a recent study, Anne Grapin-Botton, director at MPI-CBG, and her team in Dresden and at the Novo Nordisk Foundation Center for Stem Cell Biology in Copenhagen, Denmark, together with colleagues from the Faculty of Medicine Carl Gustav Carus of the Technische Universität Dresden found that the gene Wnt4 becomes active in food-sensing beta cells as they mature in early postnatal life.
The discovery of the role of Wnt4 in the development of a pancreas started in the 1990s at Harvard University, when Anne Grapin-Botton, a postdoctoral researcher at that time, discussed with Seppo Vainio, now a research unit leader at the University of Oulu. “I remember that when I worked with Wnt4 in kidney development, we speculated that this signal would have a role in the development of the pancreas too,” says Seppo Vainio. But the researchers were lacking the right tools at that time. Over 20 years later, postdoctoral researcher Keiichi Katsumoto in the lab of Anne Grapin-Botton was keen on finding out what function the gene Wnt4 has in pancreas development. In the meantime, the lab of Vainio at Oulu had further developed their mouse models: “With all these tools, we could target Wnt4 function in pancreas development and physiology with Anne Grapin-Botton’s research lab,” says Seppo Vainio.
Keiichi Katsumoto describes what he observed, “We found that the gene Wnt4 is expressed in beta cells during the maturation of the cell. The cells that start expressing Wnt4 stop proliferating and become more functional. We saw that with less Wnt4, the beta cell secretes less insulin.” The team found that even though the beta cells were able to detect sugar in the blood, they secreted less insulin in response to glucose.
“When we saw that mice without the gene Wnt4 were becoming diabetic, we knew we had found something important, but we did not understand how it was acting,” says Anne Grapin-Botton, who supervised this study. “We understood from work in other organs, notably our collaborator Seppo Vainio and his colleagues, that this gene is a signal sent by cells to others. It was exciting to find communication between beta cells in the pancreas, its conservation across several animal species and the mechanisms by which it operates, notably the profound metabolic changes it provokes in beta cells. However, we do not understand yet if beta cells release Wnt4 constantly or under special circumstances. This will be something, we want to explore in the future.”
“The results also suggest that the increase of Wnt4 shortly after birth enables beta cells to mature,” says Katsumoto. Our next step is to understand why Wnt4 becomes expressed as the cells mature.” Those results could support the development replacement beta cells for diabetes therapy with added Wnt4 to promote maturation.
Establishing Physalis as a Solanaceae model system enables genetic reevaluation of the inflated calyx syndrome
by Jia He, Michael Alonge, Srividya Ramakrishnan, Matthias Benoit, Sebastian Soyk, Nathan T Reem, Anat Hendelman, Joyce Van Eck, Michael C Schatz, Zachary B Lippman in The Plant Cell
Over 34 million people in the U.S. don’t have enough food. More diverse and adaptable crops are needed to address challenges in food production made worse by climate change. Small, sweet berries called groundcherries may not feed the country, but along with other related “orphan crops,” they could strengthen food supplies. Unfortunately, these distant relatives of tomatoes aren’t ready for large-scale production — at least not yet.
Cold Spring Harbor Laboratory (CSHL) Professor and HHMI Investigator Zachary Lippman is working to change that. Alongside CSHL and HHMI postdoc Jia He, Lippman built genetic blueprints, or models, for two types of groundcherry. These new models can guide plant geneticists toward unlocking groundcherries’ untapped potential. They may also be key in scaling up other nightshade plants for widespread use. Lippman says:
“The nightshade family encompasses more than 20 crops. There’s the major crops — potato, tomato, eggplant — and then there are minor crops, or orphan crops, which are either semi-domesticated or simply wild. A lot of those have not received a lot of research attention, but might have more potential for greater production if they could be developed further.”
Groundcherries are ideal models of the nightshade family because of their similar genetics and long evolutionary history. They’re also common in North America, easy to grow, and easy to genetically modify. But their most interesting attribute, Lippman says, might be the papery, balloon-like husk, or inflated calyx, that surrounds their berries.
“It seems to have evolved independently multiple times in flowering plants,” Lippman explains. “It’s not clear whether it’s a quirk of evolution, an adaptive trait, or both. But one thing, in my mind, is very clear — it’s one of the coolest evolutionary novelties to emerge in plants.”
Previous research on nightshades suggested genes called MADS-box were responsible for the inflated calyx’s emergence. Using the genome editing tool CRISPR on their new groundcherry models, Lippman and He switched off the MADS-box genes one by one. They found that the plants still grew an inflated calyx whether they had the genes or not. The models also allowed them to uncover a gene essential for inflated calyx development. He says:
“Without these genomic resources, it’s very hard to pinpoint the molecular mechanisms underlying some of the traits that arose through evolution. We think with our new resource, our new genomes, we can dissect this whole process.”
Lippman calls the new groundcherry models “the poster children” for what’s coming next from his lab. Their goal is to pepper the nightshade family with many new plant models, which will make it easier to improve crops through genome editing. These models will also help provide a better understanding of plants’ evolutionary development.
“Beyond improving crops, these new models can give us the means to answer the fundamental question of how new traits emerge in plants,” Lippman says. “I think Jia’s going to be the one to tackle that going forward.”
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