TL;DR
- Scientists have completed the sequences for the coast redwood and giant sequoia genomes. The research reveals genes for climate adaptation and insights into genetic basis for survival. The findings indicate that the coast redwood genome evolved from a single ancestral species.
- HIV replication in the human body requires that specific viral RNAs be packaged into progeny virus particles. A new study has found how a small difference in the RNA sequence can allow the viral RNA to be packaged for replication, creating potential targets for future HIV treatments.
- Researchers describe a breakthrough using CRISPR-Cas9, a tool that has transformed molecular biological research, but whose use in the study of adipose tissue had been elusive.
- Experts have identified a fundamental part of the immune system’s long-term memory, providing a useful new detail in the pursuit to design better vaccines for diseases, ranging from COVID-19 to malaria.
- Researchers have discovered the genetic basis for a quirk of the animal kingdom — how ant queens produce broods that are entirely male or female.
- Scientists discovered a way to transform millions of predatory bacteria into swirling flash mobs reminiscent of painter Vincent Van Gogh’s ‘The Starry Night’ as the unexpected result of experiments on a genetic circuit the creatures use to discern friend from foe.
- Researchers have investigated the genetic structure of the relic species, Acer miyabei, from three regions in Japan: Hokkaido Island and two southern groups in Northern and Central Honshu. There was significant genetic differentiation among the regions, with the northern group separated from the southern groups. Populations in the mountains of Central Honshu showed a high proportion of distinct alleles and the mountainous terrain in this area likely contributed to this genetic differentiation.
- Scientists have developed an easy way to genetically profile a cell, including human cells, and rapidly determine all DNA sequences in the genome that regulate expression of a specific gene. This can help track down upstream genes that regulate disease genes, and potentially find new drug targets. The technique involves ‘CRISPRing’ the entire genome while giving each CRISPR guide RNA a unique barcode. Deep sequencing of pooled cells uniquely identifies control genes.
- Researchers used gallic acid, an antioxidant found in gallnuts, green tea and other plants, and applied a stretching mechanism to human cartilage cells taken from arthritic knees that mimics the stretching that occurs when walking. The combination not only decreased arthritis inflammation markers in the cells but improved the production of desired proteins normally found in healthy cartilage. While still at an early stage, the findings suggest a new procedure could be developed to treat cartilage cells extracted from a patient to grow a supply of cells or a tissue to be re-implanted.
- The green pigment chlorophyll is essential to plants’ ability to generate food; but what happens if they don’t have enough of it? New work reveals the complex, interdependent nutrient responses underpinning a potentially deadly, low-chlorophyll state called chlorosis that’s associated with an anemic, yellow appearance. It could usher in more environmentally friendly agricultural practices — using less fertilizer and fewer water resources.
- 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
Assembled and annotated 26.5 Gbp coast redwood genome: a resource for estimating evolutionary adaptive potential and investigating hexaploid origin
by David B Neale, Aleksey V Zimin, Sumaira Zaman, Alison D Scott, Bikash Shrestha, Rachael E Workman, Daniela Puiu, Brian J Allen, Zane J Moore, Manoj K Sekhwal, Amanda R De La Torre, Patrick E McGuire, Emily Burns, Winston Timp, Jill L Wegrzyn, Steven L Salzberg in G3 Genes|Genomes|Genetics
Scientists have completed the sequences for the coast redwood and giant sequoia genomes. The research helps to better explain the genetic basis for these species’ ability to adapt to their changing environments. The research indicates that the coast redwood genome evolved from a single ancestral species.
The multiyear effort was conducted by researchers at University of California, Davis; Johns Hopkins University; University of Connecticut; and Northern Arizona University; and was funded by Save the Redwoods League. The research provides the foundation to better understand redwood responses to climate impacts and pathogens.
The research team previously made available the completed giant sequoia genome research in November 2020.
“It’s remarkable how far genomics research has come since we undertook this challenge in 2017,” said David Neale, plant sciences professor emeritus at UC Davis and lead author on the new coast redwood genome research. “Our work on the coast redwood and giant sequoia genomes will enable us to develop modern genetic tools that can be used in the restoration and conservation of these ecologically important tree species.”
The league and its research partners launched the Redwood Genome project in 2017. Project partners outlined an ambitious plan to fully sequence the coast redwood and giant sequoia genomes for the first time using new conifer genetic sequencing techniques.
The genomic resources and screening tools developed in this project will help researchers quickly assess evolutionary adaptive potential in these forests and ultimately inform forest restoration and management plans.
The coast redwood is the world’s tallest tree, and its genome is among the most complex sequenced. Nearly nine times larger than the human genome, it is also the second largest genome sequenced. The redwood genome has 26.5 billion base pairs of DNA, and it is hexaploid, meaning redwoods have six sets of chromosomes. Humans have 3 billion base pairs of DNA and are diploid, with two sets of chromosomes.
When comparing the coast redwood genome sequence to that of other conifers, researchers found hundreds of gene families unique to the coast redwood. Many are genes that help the trees respond to and fight stress, resist disease and repair after injury.
The giant sequoia is the world’s largest tree species and among the oldest on the planet. As reported by the research team in 2020, its genome contains 8.125 billion base pairs of DNA. Similar to the human genome, the giant sequoia genome is diploid. The reference genome produced for this study represents the first genome sequenced in the Cupressaceae family, and it lays a foundation for using genomic tools to aid in giant sequoia conservation and management.
The genomes of conifers are three to 10 times larger than the human genome. They are highly repetitive and complex. The first conifer genomes ever sequenced were the Norway spruce in 2013 and loblolly pine in 2014, 10 years after the human genome was completed.
Sequencing conifer genomes was not previously feasible due to economic and technical limitations. With technological advancements that also reduced the cost, 10 conifer genomes have now been sequenced.
In the last 160 years, commercial logging and clear-cutting claimed 95% of the coast redwood range and about one-third of the giant sequoia range. In 2020, an estimated 10%-14% of giant sequoia died from high-intensity wildfires, and in some areas the seedbank also died.
Two wildfires also burned through large sections of the giant sequoia range in 2021, and mortality from those is currently estimated to impact another 5% of the mature trees. As a result, both forests have experienced significant losses in total acreage and genetic diversity.
With these significant impacts to both populations, the league is leading restoration projects in both forest ranges. It aims to use this and future genetic research to inform efforts to restore and maintain genetic diversity and bolster the resilience of these species in the face of rapid, unprecedented environmental change.
“This ambitious scientific research provides a critical foundation for the League and the entire redwoods community,” said Joanna Nelson, Ph.D., director of science and conservation planning for Save the Redwoods League. “It will ultimately help us understand the incredible range of responses that coast redwood and giant sequoia species have exhibited in the face of climate change and how native genetic diversity has informed these responses. The Redwood Genome Project helps us see, for the first time, the full genetic diversity that has allowed these forests to adapt and survive for millennia — and could protect them against a suite of conditions they have never experienced.”
Selective packaging of HIV-1 RNA genome is guided by the stability of 5′ untranslated region polyA stem
by Olga A. Nikolaitchik, Shuohui Liu, Jonathan P. Kitzrow, Yang Liu, Jonathan M. O. Rawson, Saurabh Shakya, Zetao Cheng, Vinay K. Pathak, Wei-Shau Hu, Karin Musier-Forsyth in Proceedings of the National Academy of Sciences
HIV replication in the human body requires that specific viral RNAs be packaged into progeny virus particles. A new study has found how a small difference in the RNA sequence can allow the viral RNA to be packaged for replication, creating potential targets for future HIV treatments.
The study found that HIV chooses its viral RNA genome — the “source code” that it injects into healthy human cells to infect them — based on functions attributable to just two nucleotides.
“It’s just this two-nucleotide difference that makes such a dramatic effect,” said Karin Musier-Forsyth, senior author of the study, Ohio Eminent Scholar and a professor of chemistry and biochemistry at The Ohio State University. “If we can prevent it from packaging its own genome, we can prevent it from spreading inside the body.”
The study’s authors, who also include researchers from the National Cancer Institute, hoped to answer a long-standing question in HIV biology research: How does the virus know to package its specific viral RNA to be copied in human cells?
“Just like we need a genome encoded by DNA, viruses have their own genomic DNA or RNA — in the case of HIV it’s RNA — and they have to package their genomic RNA and that’s what this whole study is about,” she said. “It’s an essential step for how we understand the replication of the virus.”
RNA is a string of nucleotides, and it is present in some form or another in all living things, including viruses. In HIV, it carries the genetic information that allows the virus to copy itself inside a host — the human body. HIV RNA comprises about 9,800 nucleotides.
“We have lots of types of RNA in our cells as humans, including messenger RNA (mRNA), which is very abundant — and which everyone has heard about now, thanks to COVID-19,” Musier-Forsyth said. “But the viral genome from HIV is made in small amounts, and it is very selectively packaged as genomic RNA, in addition to serving as mRNA to make viral proteins. How does the virus find this genomic RNA to package and not just package any old RNA in our cells?”
Researchers believed if they could find an answer to that question, they might eventually be able to develop drugs that could block the virus from replicating and stop it from infecting healthy human cells.
The researchers examined the structures of two nearly identical HIV RNA strings and found that the virus used a two-nucleotide difference on the very end of the RNA strings to distinguish between genomic RNA and viral mRNA. One, they found, was more efficient at being packaged as a genome than the other due to the conformations, or structures, that it formed.
The findings could have implications for future HIV treatments that target RNA and would be different from current HIV treatments, which primarily target viral proteins. New HIV drugs based on this discovery are likely years away, but Musier-Forsyth said this finding is an important scientific step.
“Now that we understand more about the structure of the RNA, we could develop therapeutics, whether they be small molecules or other new nucleic acid therapeutics, that could lock the RNA into a conformation that wouldn’t be packaged. If it can’t package its genome then it can’t replicate,” Musier-Forsyth said.
BAd-CRISPR: Inducible gene knockout in interscapular brown adipose tissue of adult mice
by Steven M. Romanelli, Kenneth T. Lewis, Akira Nishii, Alan C. Rupp, Ziru Li, Hiroyuki Mori, Rebecca L. Schill, Brian S. Learman, Christopher J. Rhodes, Ormond A. MacDougald in Journal of Biological Chemistry
Fat — it is vital for life but too much can lead to a host of health problems. Studying how fat, or adipose, tissue functions in the body is critical for understanding obesity and other issues, yet structural differences in fat cells and their distribution throughout the body make doing so challenging.
“Fat cells are different from other cells in that they lack unique cell surface receptors and only account for a minority of the cells within fat tissue,” said Steven Romanelli, Ph.D., a former member in the laboratory of Ormand MacDougald, Ph.D., in the Department of Molecular & Integrative Physiology.
In a new paper, Romanelli, MacDougald and their colleagues describe a breakthrough using CRISPR-Cas9, a tool that has transformed molecular biological research, but whose use in the study of adipose tissue had been elusive.
“The biggest challenge in terms of adipose research to date has been that if you want to study a gene’s function, you have to commit a considerable amount of time, resources and money into developing a transgenic mouse,” said Romanelli.
The traditional way of developing mouse models involves breeding mice with a desired mutation to delete or introduce certain genes of interest, which Romanelli says can take more than a year and tens of thousands of dollars.
CRISPR-Cas9 has revolutionized this process. It’s a gene editing technique comprised of an enzyme called Cas9 which can break strands of DNA and a piece of RNA that guides the Cas9 enzyme to a specific site in the genome for editing. This tool is packaged into a non-harmful virus for delivery to the cells being studied. The tool has been successfully used to study heart, liver, neurons, and skin cells to name a few, but never a certain type of adipose cells known as brown fat.
Using the technique, the team was able to successfully target brown fat, a specialized adipose tissue used to generate heat and protect core body temperature.
“What we’ve been able to do is take that whole process and distill it into anywhere from two weeks to a month to generate a transgenic mouse, reducing the cost to less than $2,000. Not only does it reduce time and cost, it democratizes the research so that any lab that is familiar with molecular biology techniques can adopt this method and do it themselves,” said Romanelli.
They were also able to use this method to delete multiple genes simultaneously, a fact that could help researchers better understand important molecular pathways. Using their adeno-associated virus CRISPR-Cas9 components, they were able to knockout the UCP1 gene that defines brown adipose and enables it to generate heat, in adult mice. They observed that the knockout mice were able to adapt to the loss of the gene and maintain their body temperature in cold conditions, hinting at other pathways involved in temperature homeostasis.
Romanelli says these early results are exploratory, but the technique represents an important step forward in studying fat.
Genetic variation of a relict maple Acer miyabei Uncovering its history of disjunct occurrence and the role of mountain refugia in shaping genetic diversity
by Ikuyo Saeki, Akira S. Hirao, Tanaka Kenta in American Journal of Botany
In a recent study, researchers from the University of Tsukuba revealed that the mountainous landscape of Central Honshu, Japan, has played a role in shaping the genetic diversity of the maple species Acer miyabei.
Acer miyabei is found mainly in river floodplains, from lowland to mountainous areas. The species was once abundant but is now only found in small, isolated populations. In Japan, Acer miyabei is found in three regions: a northern group in Hokkaido with a number of local populations at low elevation, and groups in North and Central Honshu, which have smaller populations. In Central Honshu, Acer miyabei is found at high altitude in mountainous areas.
“The genetic diversity and variation of relic species, like Acer miyabei, can provide clues to their origins and history, as well as the ability of current populations to respond to climate change,” says lead author of the study, Professor Ikuyo Saeki. “We wanted to explore the biogeographic history ofthis species, which was once widespread, to understand how it has survived in these pockets of suitable habitat.”
To look at the genetic variation of trees from the three regions, the researchers collected samples from 604 trees at 43 sites. They then examined their genetic structure using microsatellite markers.
While the results showed genetic differentiation among the three regions, the variation among populations within regions was larger than that among regions. “The northern group could be differentiated from the two southern groups, but our findings suggest that division of the populations occurred relatively recently,” explains Professor Saeki. “It appears that the mountainous terrain of Central Honshu likely played an important role in shaping the genetic variation of populations in that region.”
While Central Honshu has a small number of geographically scattered populations, these have a high number of distinct alleles-a sign of genetic diversity. As the climate warmed after the glacial periods of the last ice age, the cool higher elevations of the mountains may have provided refugia for Acer miyabei. Genetic flow between these populations may then have been limited by the terrain.
Species distributions can be shaped by many different climatic, environmental, and biological factors and the relationships among them over time. Looking at the genetic structure of relic species, like Acer miyabei, can provide insights into the relationships between genetics and the environment, as well as insights into how species may adapt to future change.
B cell–intrinsic TBK1 is essential for germinal center formation during infection and vaccination in mice
by Michelle S.J. Lee, Takeshi Inoue, Wataru Ise, Julia Matsuo-Dapaah, James B. Wing, Burcu Temizoz, Kouji Kobiyama, Tomoya Hayashi, Ashwini Patil, Shimon Sakaguchi, A. Katharina Simon, Jelena S. Bezbradica, Satoru Nagatoishi, Kouhei Tsumoto, Jun-Ichiro Inoue, Shizuo Akira, Tomohiro Kurosaki, Ken J. Ishii, Cevayir Coban in Journal of Experimental Medicine
Experts in Japan have identified a fundamental part of the immune system’s long-term memory, providing a useful new detail in the pursuit to design better vaccines for diseases, ranging from COVID-19 to malaria. The research reveals a new role for the enzyme TBK1 in deciding the fate of immune system memory B cells.
The immune system is made of many cell types, but the two types relevant for this University of Tokyo research project are white blood cells called CD4+ follicular helper T cells and B cells. After the body recognizes an infection, the follicular helper T cells release chemical signals that cause immature B cells to learn and remember what pathogens to attack. This process of T-to-B cell signaling and B cell training occurs within a temporary cell structure called the germinal center in organs of the immune system, including the spleen, lymph nodes and tonsils. Memory B cells developed within the germinal center memorize a pathogen the first time it infects you and then if it ever gets into your body again, the mature, trained memory B cells attack it by inducing antibody production before the pathogen can multiply, saving you from feeling sick a second time.
“A goal of vaccination is to produce high-quality memory B cells for long-lasting antibody production,” said Project Assistant Professor Michelle S. J. Lee from the UTokyo Institute of Medical Science, first author of the recent publication.
“There are many factors to consider when designing vaccines for long-lasting immunity, so we should not focus only on the germinal center alone. But if you don’t have a functional germinal center, then you will be very susceptible to reinfection,” said Lee.
However, there is no limit to the number of times you can be bitten by mosquitoes and reinfected by the malaria parasite. Somehow, malaria parasites escape memory B cells. Although children are more likely to die from malaria than adults, some people can become severely ill despite any number of previous malaria infections.
This ability of the parasite to prevent and evade effective B cells is what makes malaria an interesting pathogen for Professor Cevayir Coban, who leads the Division of Malaria Immunology at the UTokyo Institute of Medical Science and is last author of the research paper with Lee and collaborators.
“We want to understand the fundamentals of the natural immune response. Whatever we do should aim to eventually benefit malaria patients,” said Coban. “The COVID-19 pandemic brought global attention to infectious diseases and interest in vaccine design, so we have a chance to renew the focus on neglected diseases like malaria,” she continued.
Over many years, the scientific community has identified a wide range of roles for the molecule TBK1, an enzyme that can alter the activity of genes or other proteins by adding chemical tags, through a process called phosphorylation. TBK1 has well-known roles in antiviral immunity. However, no research group had connected TBK1 to B cell fate and the germinal center.
Researchers genetically modified mice that had nonfunctional TBK1 genes only in specific types of cells, primarily either B cells or CD4+ T cells. This cell type-specific knockout of TBK1 gives researchers a clearer idea of what a gene with many jobs is doing in different cells of the body. Coban, Lee and their colleagues infected these modified mice and healthy adult mice with the malaria parasite, observed their health, and then examined samples of their spleens and lymph nodes.
Microscopy images revealed that germinal centers only form in mice that have functional TBK1 in their B cells. Mice with no TBK1 in their B cells were more likely to die and died sooner from the malaria infection than their normal peers. Additional experiments showed that the few mice who survived malaria with no TBK1 in their B cells were able to use other types of immune responses, but they can become reinfected. However, deleting TBK1 only from the CD4+ follicular helper T cells had no effect on the germinal centers or how the mice fared with a malaria infection.
Further analysis confirmed that without TBK1, many proteins in immature B cells had abnormal phosphorylation compared to normal immature B cells. For different genes, abnormal phosphorylation can cause either abnormal increases or decreases in activity. Researchers suspect that in B cells, TBK1 activity acts as an off switch for certain genes, essentially turning off genes that trap the B cells in their immature state.
“This is the first time to show TBK1 is essential in B cells to form the germinal centers and produce high-quality, mature antibodies,” said Lee.
Researchers are hopeful that eventually, with more fundamental knowledge about the remaining mysteries of the immune system, future vaccines can be designed to produce longer-lasting immunity, potentially without needing multiple doses of vaccine. However, vaccine design will always be complicated by the unique qualities of each pathogen and its mutated versions, especially in the case of rapidly evolving pathogens like Sars-CoV-2, the virus causing COVID-19.
“For now, we can at least say that an effective vaccine tailored to produce long-lasting protective immunity should not reduce TBK1 activity in B cells,” said Coban.
Combining stretching and gallic acid to decrease inflammation indices and promote extracellular matrix production in osteoarthritic human articular chondrocytes
by Haneen A. Abusharkh, Olivia M. Reynolds, Juana Mendenhall, Bulent A. Gozen, Edwin Tingstad, Vincent Idone, Nehal I. Abu-Lail, Bernard J. Van Wie in Experimental Cell Research
A healthy diet and a little exercise appear to be good for arthritis, even on the cellular level.
A team led by Washington State University researchers used gallic acid, an antioxidant found in gallnuts, green tea and other plants, and applied a stretching mechanism to human cartilage cells taken from arthritic knees that mimics the stretching that occurs when walking. The combination not only decreased arthritis inflammation markers in the cells but improved the production of desired proteins normally found in healthy cartilage.
While still at an early stage, the findings suggest a new procedure could be developed to treat cartilage cells extracted from a patient to grow a supply of cells or a tissue to be re-implanted.
“We found the combined stretching, which acts like an exercise for the cell itself, with the gallic acid decreased inflammation markers, which means we were able to reverse osteoarthritis,” said Haneen Abusharkh, the study’s lead author and a recent WSU Ph.D. graduate. “It’s basically like having good exercise and a good diet on a micro-scale.”
For the study the researchers harvested osteoarthritic cartilage cells from donated knees taken out during joint replacement surgery at Pullman Regional Hospital. They cultured the cells in the lab and first tested six antioxidant “nutraceuticals,” or nutritional products, including Vitamin C, Vitamin E and curcumin. Antioxidants can neutralize free radicals, unstable atoms that result from oxidative stress which can damage cells and tissues.
The laboratory tests suggested gallic acid as the most effective antioxidant for neutralizing the free radicals in the osteoarthritic cartilage cells. The researchers then applied the gallic acid and added stretching, using a cytostretcher developed by the company Curi Bio Inc. They set stretching to 5%, a level that matches the stretch in human knees when walking.
The combination decreased inflammation markers known as matrix metalloproteinases. It increased the deposition of collagen and glycosaminoglycans, which are compounds that give connective tissue its integrity, tensile strength and resistance to compressive forces from body weight on the joints. The stretching and gallic acid also increased the expression of two other cartilage-specific proteins.
Osteoarthritis, the most common musculoskeletal disorder in the world, destroys cartilage in joints causing pain and limiting movement. As of yet there is no complete cure, and treatments range from prescribing pain killers to replacing the joint surgically with a synthetic one, but even the surgery does not allow the patient to return to a full range of motion.
Another procedure is called autologous chondrocyte implantation, or ACI, which involves removing cartilage cells from the joint, growing them to large numbers and then re-implanting them. Currently, the cells are not treated before re-implantation, the researchers noted, and the lack of treatment results in cells growing a weaker fibrocartilage. They can also remain affected by osteoarthritis, and these procedures do not return full functionality to the joint. This study shows a potential way to develop a similar procedure by first treating the cartilage cells while growing them into a tissue that could then be re-implanted.
“We are advancing techniques to make regenerative cartilage in the laboratory that could potentially be implanted into cartilage lesions, so that joint replacements would decrease in number,” said Bernard Van Wie, WSU professor in the Voiland School of Chemical Engineering and Bioengineering and the study’s principal investigator and corresponding author. “We’re looking to develop a natural cartilage that works properly from the beginning, rather than replacing the joint.”
The study adds evidence that it may be good to eat foods high in antioxidants — and to exercise, although the researchers caution that gallic acid should not be seen as a miracle cure, and any course of action should be taken only in consultation with a person’s doctor.
“This provides some evidence that a good diet and an exercise actually work,” said Abusharkh. “Even for people who have mild osteoarthritis, it’s really good to exercise. It’s very bad for our cartilage tissue to just lay down or sit the whole day; we have to have a little bit of activity.”
Linked supergenes underlie split sex ratio and social organization in an ant
by German Lagunas-Robles, Jessica Purcell, Alan Brelsford in Proceedings of the National Academy of Sciences
Researchers have discovered the genetic basis for a quirk of the animal kingdom — how ant queens produce broods that are entirely male or female.
“It’s weird to have any parent that’s only producing one sex or the other,” said UC Riverside entomologist and study author Jessica Purcell.
Scientists have known for some time that ant colonies can specialize in producing all-male or all-female offspring. For the first time, UC Riverside scientists have located a set of genes on a single chromosome that are associated with this phenomenon.
When humans mate, both parents contribute one copy of the genome to their offspring. However, female ants are the only ones that carry two copies, like humans and most other animals do, whie the males carry only one copy.
“Male ants develop from unfertilized eggs their mother lays,” said UCR evolutionary biologist and senior study author Alan Brelsford. “Therefore, male ants, as well as bees and wasps, genetically have a mother but no father.”
Purcell and Brelsford found their study specimens in 2016 while on a journey to collect and study ants from Riverside all the way to the Arctic Circle. In northern Canada’s Yukon territory, they found more than 100 colonies of two Formica ant species that appeared ready for their annual reproductive flights. Back in Riverside, ecology doctoral student German Lagunas-Robles analyzed the genomes of these ants, looking for differences between male-producing and female-producing colonies.
During mating flights, a queen will mate, land, chew off her own wings, and look for a place to burrow. She’ll lay roughly a dozen eggs in that burrow, which then develop into her first brood of workers. These worker ants are always female, but they won’t reproduce. Once they’ve matured, the workers take over foraging for food, and the queen continues to reproduce, laying hundreds of eggs per day.
While the males live for only a few hours after their mating flight, the queen will store their sperm and can use it over the course of the next decade to produce new offspring. The majority of the young in an ant colony are wingless workers, but in mature colonies, queens will also produce offspring that can fly. Though the researchers found genes associated with which sex of offspring is produced, genetics may not be the only way that queens can influence the sex of their colonies. They could decide not to use their stored sperm, which would result in male ants. Workers could also manipulate the sex ratio of a colony by not feeding or selectively killing certain larvae.
Other studies have documented that the availability of food also has an effect on the sex of an ant colony. “When extra food is dumped on a colony, it produces fewer males,” Brelsford said. The research team wants to conduct additional studies to learn when genes or environmental factors play a bigger role in determining the sex of offspring.
The team also wants to study how these genes work in different environments. Such details could ultimately help preserve beneficial native North American ants. Mating flights tend to coincide with specific seasons and temperatures. Climate change could affect food availability, the timing of breeding, and generally throw the sex ratio of a population out of balance. Unlike their invasive, non-native pesky relatives, these species rarely bother humans, and perform important environmental functions.
“Ants are really integral to ecosystems as one of the most abundant insects,” Purcell said. “Gardeners tend to love earthworms, but ants do similar things to enhance soil health.”
Emergent Myxobacterial Behaviors Arise from Reversal Suppression Induced by Kin Contacts
by Rajesh Balagam, Pengbo Cao, Govind P. Sah, Zhaoyang Zhang, Kalpana Subedi, Daniel Wall, Oleg A. Igoshin in mSystems
Scientists discovered a way to transform millions of predatory bacteria into swirling flash mobs reminiscent of painter Vincent Van Gogh’s “The Starry Night” as the unexpected result of experiments on a genetic circuit the creatures use to discern friend from foe.
Myxococcus xanthus has been studied for decades as a model system for social cooperation and bacterial gene regulation. While studying M. xanthus mutants that overexpress two proteins the cells use to recognize close relatives, researchers from Rice University and the University of Wyoming discovered a previously unreported behavior: self-organization into circles a millimeter or more in diameter.
“When you overexpress that protein, you can see these circular aggregates emerge after four hours, and by 12 hours they take up the whole (petri dish),” said study co-author Oleg Igoshin, a professor of bioengineering at Rice and senior scientist at Rice’s Center for Theoretical Biological Physics.
Igoshin’s research group and the Wyoming microbiology group led by co-author Daniel Wall collaborated for five years on the study, conducting dozens of laboratory and computational experiments to uncover the genetic mechanism of the circular swarms . M. xanthus prey on other bacteria. Lacking internal organs to digest their prey, they band together in familial packs to engulf and devour victims, which can include M. xanthus that aren’t members of the family.
About five years ago, Wall and study co-author Pengbo Cao, then a graduate student in his lab and now a postdoctoral research associate at the Georgia Institute of Technology, showed M. xanthus uses a surface receptor called TraA and a partner protein called TraB to recognize kin. When M. xanthus bumps into a close relative, the TraAB complex acts as a kind of glue, forming a sticky bond between the two. When M. xanthus runs into unrelated M. xanthus, TraAB helps poison non-kin.
While investigating the mechanism of TraAB, Wall’s team created several mutant strains, including some that overexpressed TraAB, making more of the protein than normal, and Cao noticed they had a tendency to form cell clusters within a few hours. While Wall’s team followed up with microbiological experiments, Igoshin’s group was asked if it could create a theoretical model that might explain the mystery.
“What’s interesting about our theory is that the only way we see these (circular aggregates) in our simulations is when we make the cells non-reversing,” Igoshin said. “In normal wild-type cells, they go back and forth, back and forth, like a commuter train. The head becomes the tail and the tail becomes the head. And they do it every eight minutes or so.”
The model simulated M. xanthus behavior based on changes to TraAB and other signaling circuits and was developed by Igoshin and study co-authors Rajesh Balagam and Zhaoyang Zhang , who were then graduate students in his lab.
“Our first idea was maybe they’re so sticky, they just can’t reverse,” Igoshin said. “So we tried to see if sticky cells that normally reverse would form circular aggregates. We added a very, very strong adhesion to our simulations, and nothing happened. They didn’t make circles. However, if we instead inhibited the reversals the simulations worked. Circular aggregates emerged.”
Follow-up experiments at Wyoming verified cells in the aggregates did not reverse, but that raised even more questions.
“Somehow TraAB overexpression in aggregates prevented cells from reversing,” Igoshin said. “So this was very cool for us, because this is what our model predicted. But this was also a bit puzzling and completely unexpected. Because TraAB, as far as we knew, didn’t have anything to do with reversal regulation.”
A few possible explanations were ruled out with follow-up experiments. Evidence suggested TraAB stickiness could be the key.
“But how is it that adhesion suppresses the reversals?” Igoshin said. “Our idea was maybe there is some sort of contact-dependent signal between cells that suppresses the reversals. The cells are in dense groups and are in contact with others all the time, but those contacts are transient. But if TraAB overexpression really makes you sticky, your neighbor will remain your neighbor for longer, and that could trigger the signal that suppresses the reversals.”
With those changes, the model began producing patterns very similar to what Wall’s team was seeing in its experiments with engineered M. xanthus strains. To see if the model could predict a behavior that hadn’t yet been seen in experiments, Igoshin’s team simulated what would happen in mixed colonies of M. xanthus, including mixtures of two extra-sticky mutants that didn’t recognize one another as kin. The model predicted they would form large rotating swarms containing mixtures of the two strains.
The prediction was borne out in experiments by Wall’s team, and the application of false color to microscopic images of the colonies revealed M. xanthus’ pastiche of “The Starry Night.”
“Our work highlights how a social bacterium, known for rich sources of therapeutic natural products and as crop biocontrol agents, serves as a powerful model for studying emergent behaviors that also exhibit artistic beauty,” Wall said.
CiBER-seq dissects genetic networks by quantitative CRISPRi profiling of expression phenotypes
by Ryan Muller, Zuriah A. Meacham, Lucas Ferguson, Nicholas T. Ingolia in Science
CRISPR-Cas9 makes it easy to knock out or tweak a single gene to determine its effect on an organism or cell, or even another gene. But what if you could perform several thousand experiments at once, using CRISPR to tweak every gene in the genome individually and quickly see the impact of each?
A team of University of California, Berkeley, scientists has developed an easy way to do just that, allowing anyone to profile a cell, including human cells, and rapidly determine all the DNA sequences in the genome that regulate the expression of a specific gene.
While the technique will mostly benefit basic researchers who are interested in tracking the cascade of genetic activity — the genetic network — that impacts a gene they’re interested in, it will also help researchers quickly find the regulatory sequences that control disease genes and possibly find new targets for drugs.
“A disease where you might want to use this approach is cancer, where we know certain genes that those cancer cells express, and need to express, in order to survive and grow,” said Nicholas Ingolia, UC Berkeley associate professor of molecular and cell biology. “What this tool would let you do is ask the question: What are the upstream genes, what are the regulators that are controlling those genes that we know about?”
Those controllers may be easier to target therapeutically in order to shut down the cancer cells. The new technique simplifies something that has been difficult to do until now: backtrack along genetic pathways in a cell to find these ultimate controllers.
“We have a lot of good ways of working forward,” he said. “This is a nice way of working backward, figuring out what is upstream of something. I think it has a lot of potential uses in disease research.”
“I sometimes use the analogy that when we walk into a dark room and flip a light switch, we can see what light gets switched on. That light is like a gene, and we can tell, when we flip the switch, what genes it turns on. We are already very good at that,” he added. “What this lets us do is work backward. If we have a light we care about, we want to find out what are the switches that control it. This gives us a way to do that.”
Since the advent of CRISPR-Cas9 gene-editing eight years ago, researchers who want to determine the function of a specific gene have been able to precisely target it with the Cas9 protein and knock it out. Guided by a piece of guide RNA complementary to the DNA in the gene, the Cas9 protein binds to the gene and cuts or, as with CRISPR interference (CRISPRi), inhibits it.
In the crudest type of assay, the cell or organism either lives or dies. However, it’s possible to look for more subtle effects of the knockout, such as whether a specific gene is turned on or off, or how much it’s turned up or down.
Today, that requires adding a reporter gene — often one that codes for a green fluorescent protein — attached to an identical copy of the promoter that initiates expression of the gene you’re interested in. Since each gene’s unique promoter determines when that gene is expressed, if the Cas9 knockout affects expression of your gene of interest, it will also affect expression of the reporter, making the culture glow green under fluorescent light. Nevertheless, with 6,000 total genes in yeast — and 20,000 total genes in humans — it’s a big undertaking to tweak each gene and discover the effect on a fluorescent reporter.
“CRISPR makes it easy to comprehensively survey all the genes in the genome and perturb them, but then the big question is, How do you read out the effects of each of those perturbations?” he said.
This new technique, which Ingolia calls CRISPR interference with barcoded expression reporter sequencing, or CiBER-seq, solves that problem, allowing these experiments to be done simultaneously by pooling tens of thousands of CRISPR experiments. The technique does away with the fluorescence and employs deep sequencing to directly measure the increased or decreased activity of genes in the pool. Deep sequencing uses high-throughput, long-read next generation sequencing technology to sequence and essentially count all the genes expressed in the pooled samples.
“In one pooled CiBER-seq experiment, in one day, we can find all the upstream regulators for several different target genes, whereas, if you were to use a fluorescence-based technique, each of those targets would take you multiple days of measurement time,” Ingolia said.
CRISPRing each gene in an organism in parallel is straightforward, thanks to companies that sell ready-made, single guide RNAs to use with the Cas9 protein. Researchers can order sgRNAs for every gene in the genome, and for each gene, a dozen different sgRNAs — most genes are strings of thousands of nucleotides, while sgRNAs are about 20 nucleotides long.
The team’s key innovation was to link each sgRNA with a unique, random nucleotide sequence — essentially, a barcode — connected to a promoter that will only transcribe the barcode if the gene of interest is also switched on. Each barcode reports on the effect of one sgRNA, individually targeting one gene out of a complex pool of thousands of sgRNAs. Deep sequencing tells you the relative abundances of every barcode in the sample — for yeast, some 60,000 — allowing you to quickly assess which of the 6,000 genes in yeast has an effect on the promoter and, thus, expression of the gene of interest. For human cells, a researcher might insert more than 200,000 different guide RNAs, targeting each gene multiple times.
“This is really the heart of what we were able to do differently: the idea that you have a big library of different guide RNAs, each of which is going to perturb a different gene, but it has the same query promoter on it — the response you are studying. That query promoter transcribes the random barcode that we link to each guide,” he said. “If there is a response you care about, you poke each different gene in the genome and see how the response changes.”
If you get one barcode that is 10 times more abundant than any of the others, for example, that tells you that that query promoter is switched on 10 times more strongly in that cell. In practice, Ingolia attached about four different barcodes to each guide RNA, as a quadruple check on the results.
“By looking more directly at a gene expression response, we can pick up on a lot of subtlety to the physiology itself, what is going on inside the cell,” he said.
In the newly reported experiments, the team queried five separate genes in yeast, including genes involved in metabolism, cell division and the cell’s response to stress. While it may be possible to study up to 100 genes simultaneously when CRISPRing the entire genome, he suspects that, for convenience, researchers would limit themselves to four or five at once.
Interdependent iron and phosphorus availability controls photosynthesis through retrograde signaling
by Hye-In Nam, Zaigham Shahzad, Yanniv Dorone, Sophie Clowez, Kangmei Zhao, Nadia Bouain, Katerina S. Lay-Pruitt, Huikyong Cho, Seung Y. Rhee, Hatem Rouached in Nature Communications
Green is a color that is almost universally associated with plants — for good reason. The green pigment chlorophyll is essential to plants’ ability to generate food; but what happens if they don’t have enough of it?
New work from Carnegie, Michigan State University, and the National Research Institute for Agriculture, Food and Environment in France reveals the complex, interdependent nutrient responses underpinning a potentially deadly, low-chlorophyll state called chlorosis that’s associated with an anemic, yellow appearance. Their findings could usher in more environmentally friendly agricultural practices — using less fertilizer and fewer water resources.
Photosynthesis is the complex biochemical process by which plant cells convert the Sun’s energy into chemical energy, which then is used to fix carbon dioxide from the atmosphere into sugar molecules. It occurs inside highly specialized plant cell organelles called chloroplasts.
Nutrients accumulate in chloroplasts and are essential to their optimal functioning. The research team — led by MSU’s Hatem Rouached and including Carnegie’s Sue Rhee, Hye-In Nam, Yanniv Dorone, Sophie Clowez, and Kangmei Zhao — showed that a balance of both iron and phosphorus are necessary to prevent chlorosis. The project was initiated when Rouached was a visiting scholar at Carnegie from France.
“For a long time, experts have thought that low iron is the sole cause of chlorosis and farmers have often applied iron to combat leaf yellowing,” Rhee explained. “But recent work has shown that other nutrients play a role in bringing about this anemic reaction.”
To better understand what makes leaves chlorotic, the investigators decided to look at the response to multiple nutrients in concert, rather than one by one. They found that plants showing chlorosis induced by iron deficiency would yellow and photosynthetic activity would be affected, as expected. However, when the nutrient phosphorus was also removed, the plant’s leaves started accumulating chlorophyll and turned green again.
The explanation for this unexpected response lies in the signaling between the chloroplast, where photosynthesis occurs, and the cell’s nucleus, where its genetic code is stored. Interdisciplinary analyses indicated that the nucleus’ ability to regulate gene expression in response to low iron depends on the availability of phosphorus. This kind of complex layering of nutrient responses shows that there is much still to learn about these communication channels between these two crucial plant organelles.
The team’s findings could have implications for resilience in food crops — especially crucial in a changing climate.
“We need to rethink fertilizer management, for example,” Rouached concluded. “If we take actions that don’t consider how the nutrients interact with each other, we potentially create conditions that set plants up to fail. It’s critical that we correct this thinking moving forward for the benefit of food production worldwide.”
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