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Transformed: the plant whose sex life fascinated Charles Darwin

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Researchers have genetically transformed the Common Primrose (Primula vulgaris) for the first time in a development that could shed light on one of the plant world's most renowned reproductive systems.

Transformed: the plant whose sex life fascinated Charles Darwin
Credit: John Innes Historical Collection
The complicated sex life of Primula was a subject that fascinated Charles Darwin and generations of geneticists that followed because it's one of the best examples of heteromorphic flower development.

Heteromorphy (or heterostyly) is a phenomenon in which plants exhibit two or three distinct forms of flowers based on the position of the male and female sex organs. Now, some of the secrets that eluded Darwin could be revealed following the biotechnological success announced by researchers from the John Innes Centre, the University of East Anglia (UEA) and the Earlham Institute.

The technology known as Agrobacterium-mediated plant transformation involves using soil bacteria to insert or modify genes in a plant genome. Genetic transformation is a valuable tool that allows researchers to study gene function and genetically controlled characteristics in organisms.

It is a research method routinely used on model organisms such as Nicotiana benthamiana and Arabidopsis thaliana to understand the molecular workings of plants. However, these species cannot be used to study heteromorphy because their flowers are all homomorphic which means they are able to self-fertilise.


"Now we have a transformation system we can use gene editing tools such as CRISPR-Cas9 to work out exactly what the gene function is that controls heteromorphy in the Primula family," says Sadiye Hayta, of the John Innes Centre.

"Longer term, there may be implications for commercial crops. If we understand the roles of these different genes we could take them over to a commercial crop and use it in a hybrid system," she adds.

Until now attempts to transform Primula have been unsuccessful because the plant has proved resistant to laboratory regeneration of whole plants from tissue culture.

The new transformation protocols reported in the peer-reviewed journal Plant Methods will allow the scientists of today to study the Primula at a molecular level.

The flowering plant is one of the best-known examples of heteromorphic flower development. This reproductive system enthralled not only Darwin but many leading geneticists from the early 1900s including William Bateson, the first director of the John Innes Centre and colleagues JBS Haldane, Cyril Darlington and Dorothea de Winton.


Darwin, in a landmark paper of 1862, worked out the functional significance of the different anatomical formations: they made the plants self-incompatible. This is Nature's way of promoting cross-pollination to maintain genetic variation in the population, driving natural selection.

Fundamental research into heteromorphy has continued. In a research paper in 2016 a John Innes Centre - University of East Anglia team led by Professor Philip Gilmartin identified the S-Locus supergene that controls heteromorphy as described by Darwin.

Armed with this fundamental knowledge and a the newly announced transformation system, scientists can delve deeper into the mysteries of heteromorphy.

Co-author Mark Smedley, of the John Innes Centre says: "It is not every day you get to work on a paper that references Darwin. This is a fundamental story that scientists have been trying to unravel for 200 years."


Professor Philip Gilmartin of the UEA whose laboratory started out on this scientific mission more than 20 years ago, said: "The development of a Primula transformation system is an important component of our lab's long-term study to identify and characterise the genes that control development of the two forms of Primula flower studied by Charles Darwin."

It's a piece of research that would have excited Darwin. Towards the end of his illustrious career the author of On the Origin of Species remarked:

"I do not think anything in my scientific life has given me so much satisfaction as making out the meaning of the structure of these plants."

Source: John Innes Centre [December 11, 2018]

Life in deep Earth totals 15 to 23 billion tons of carbon - hundreds of times more than humans

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Barely living "zombie" bacteria and other forms of life constitute an immense amount of carbon deep within Earth's subsurface -- 245 to 385 times greater than the carbon mass of all humans on the surface, according to scientists nearing the end of a 10-year international collaboration to reveal Earth's innermost secrets.

Life in deep Earth totals 15 to 23 billion tons of carbon - hundreds of times more than humans
A nematode (eukaryote) in a biofilm of microorganisms. This unidentified nematode (Poikilolaimus sp.) from Kopanang gold
mine in South Africa, lives 1.4 km below the surface [Credit: Gaetan Borgonie, Extreme Life Isyensya, Belgium]
On the eve of the American Geophysical Union's annual meeting, scientists with the Deep Carbon Observatory today reported several transformational discoveries, including how much and what kinds of life exist in the deep subsurface under the greatest extremes of pressure, temperature, and low nutrient availability.

Drilling 2.5 kilometers into the seafloor, and sampling microbes from continental mines and boreholes more than 5 km deep, scientists have used the results to construct models of the ecosystem deep within the planet.


With insights from now hundreds of sites under the continents and seas, they have approximated the size of the deep biosphere -- 2 to 2.3 billion cubic km (almost twice the volume of all oceans) -- as well as the carbon mass of deep life: 15 to 23 billion tonnes (an average of at least 7.5 tonnes of carbon per cu km subsurface).

The work also helps determine types of extraterrestrial environments that could support life.

Among many key discoveries and insights:

- The deep biosphere constitutes a world that can be viewed as a sort of "subterranean Galapagos" and includes members of all three domains of life: bacteria and archaea (microbes with no membrane-bound nucleus), and eukarya (microbes or multicellular organisms with cells that contain a nucleus as well as membrane-bound organelles)

- Two types of microbes -- bacteria and archaea -- dominate Deep Earth. Among them are millions of distinct types, most yet to be discovered or characterized. This so-called microbial "dark matter" dramatically expands our perspective on the tree of life. Deep Life scientists say about 70% of Earth's bacteria and archaea live in the subsurface

- Deep microbes are often very different from their surface cousins, with life cycles on near-geologic timescales, dining in some cases on nothing more than energy from rocks

- The genetic diversity of life below the surface is comparable to or exceeds that above the surface


- While subsurface microbial communities differ greatly between environments, certain genera and higher taxonomic groups are ubiquitous -- they appear planet-wide

- Microbial community richness relates to the age of marine sediments where cells are found -- suggesting that in older sediments, food energy has declined over time, reducing the microbial community

- The absolute limits of life on Earth in terms of temperature, pressure, and energy availability have yet to be found. The records continually get broken. A frontrunner for Earth's hottest organism in the natural world is Geogemma barossii, a single-celled organism thriving in hydrothermal vents on the seafloor. Its cells, tiny microscopic spheres, grow and replicate at 121 degrees Celsius (21 degrees hotter than the boiling point of water). Microbial life can survive up to 122°C, the record achieved in a lab culture (by comparison, the record-holding hottest place on Earth's surface, in an uninhabited Iranian desert, is about 71°C -- the temperature of well-done steak)

- The record depth at which life has been found in the continental subsurface is approximately 5 km; the record in marine waters is 10.5 km from the ocean surface, a depth of extreme pressure; at 4000 meters depth, for example, the pressure is approximately 400 times greater than at sea level

- Scientists have a better understanding of the impact on life in subsurface locations manipulated by humans (e.g., fracked shales, carbon capture and storage)

Life in deep Earth totals 15 to 23 billion tons of carbon - hundreds of times more than humans
Candidatus Desulforudis audaxviator (the purplish, blue rod-shaped cells straddling orange carbon spheres) is a species
of bacteria that survives on hydrogen. Scientists found it living within a fluid and gas-filled fracture 2.8 km beneath Earth's
surface at a mine near Johannesburg, South Africa. The genus name Desulforudis comes from the Latin for "from sulfur"
 and "rod," noting its shape and its ability to get energy from sulfates. And audaxviator? From Jules Verne's Journey to
the Center of the Earth, and a message in Latin deciphered by Verne's protagonist, Professor Lidenbrock, which read
 in part: "descend, bold traveler, and attain the center of the Earth" [Credit: Greg Wanger, California Institute
of Technology, USA, and Gordon Southam University of Queensland, Australia]
Ever-increasing accuracy and the declining cost of DNA sequencing, coupled with breakthroughs in deep ocean drilling technologies (pioneered on the Japanese scientific vessel Chikyu, designed to ultimately drill far beneath the seabed in some of the planet's most seismically-active regions) made it possible for researchers to take their first detailed look at the composition of the deep biosphere.

There are comparable efforts to drill ever deeper beneath continental environments, using sampling devices that maintain pressure to preserve microbial life (none thought to pose any threat or benefit to human health).

To estimate the total mass of Earth's subcontinental deep life, for example, scientists compiled data on cell concentration and microbial diversity from locations around the globe.

Led by Cara Magnabosco of the Flatiron Institute Center for Computational Biology, New York, and an international team of researchers, subsurface scientists factored in a suite of considerations, including global heat flow, surface temperature, depth and lithology -- the physical characteristics of rocks in each location -- to estimate that the continental subsurface hosts 2 to 6 × 10^29 cells.

Combined with estimates of subsurface life under the oceans, total global Deep Earth biomass is approximately 15 to 23 petagrams (15 to 23 billion tonnes) of carbon.


Says Mitch Sogin of the Marine Biological Laboratory Woods Hole, USA, co-chair of DCO's Deep Life community of more than 300 researchers in 34 countries: "Exploring the deep subsurface is akin to exploring the Amazon rainforest. There is life everywhere, and everywhere there's an awe-inspiring abundance of unexpected and unusual organisms.

"Molecular studies raise the likelihood that microbial dark matter is much more diverse than what we currently know it to be, and the deepest branching lineages challenge the three-domain concept introduced by Carl Woese in 1977. Perhaps we are approaching a nexus where the earliest possible branching patterns might be accessible through deep life investigation.

"Ten years ago, we knew far less about the physiologies of the bacteria and microbes that dominate the subsurface biosphere," says Karen Lloyd, University of Tennessee at Knoxville, USA. "Today, we know that, in many places, they invest most of their energy to simply maintaining their existence and little into growth, which is a fascinating way to live.

"Today too, we know that subsurface life is common. Ten years ago, we had sampled only a few sites - the kinds of places we'd expect to find life. Now, thanks to ultra-deep sampling, we know we can find them pretty much everywhere, albeit the sampling has obviously reached only an infinitesimally tiny part of the deep biosphere."

"Our studies of deep biosphere microbes have produced much new knowledge, but also a realization and far greater appreciation of how much we have yet to learn about subsurface life," says Rick Colwell, Oregon State University, USA. "For example, scientists do not yet know all the ways in which deep subsurface life affects surface life and vice versa. And, for now, we can only marvel at the nature of the metabolisms that allow life to survive under the extremely impoverished and forbidding conditions for life in deep Earth."

"A decade ago, we had no idea that the rocks beneath our feet could be so vastly inhabited. Experimental investigations told us that microbes could potentially survive to great depth; at that time, we had no evidence, and this has become real ten years later. This is simply fascinating and will surely foster enthusiasm to look for the biotic-abiotic fringe on Earth and elsewhere," said Isabelle Daniel, University of Lyon 1, France.

Life in deep Earth totals 15 to 23 billion tons of carbon - hundreds of times more than humans
This is a species of Methanobacterium, which produces methane. Found in samples from a buried coal bed 2 km below the
 Pacific Ocean floor off the coast of Japan, this specimen was retrieved during an Integrated Ocean Drilling Program
 (now the International Ocean Discovery Program) expedition aboard the Drilling Vessel Chikyu. Bar
represents 10 μm (micrometers, or 0.0004 inch) [Credit: Hiroyuki Imachi (Japan Agency
for Marine-Earth Science and Technology (JAMSTEC)]
Among the many remaining enigmas of deep life on Earth:

Movement: How does deep life spread -- laterally through cracks in rocks? Up, down? How can deep life be so similar in South Africa and Seattle, Washington? Did they have similar origins and were separated by plate tectonics, for example? Or do the communities themselves move? What roles do big geological events (such as plate tectonics, earthquakes; creation of large igneous provinces; meteoritic bombardments) play in deep life movements?

Origins: Did life start deep in Earth (either within the crust, near hydrothermal vents, or in subduction zones) then migrate up, toward the sun? Or did life start in a warm little surface pond and migrate down? How do subsurface microbial zombies reproduce, or live without dividing for millions to tens of millions of years?

Energy: Is methane, hydrogen, or natural radiation (from uranium and other elements) the most important energy source for deep life? Which sources of deep energy are most important in different settings? How do the absence of nutrients, and extreme temperatures and pressure, impact microbial distribution and diversity in the subsurface?


"Even in dark and energetically challenging conditions, intraterrestrial ecosystems have uniquely evolved and persisted over millions of years. Expanding our knowledge of deep life will inspire new insights into planetary habitability, leading us to understand why life emerged on our planet and whether life persists in the Martian subsurface and other celestial bodies,"  according to Fumio Inagaki, Japan Agency for Marine-Earth Science and Technology.

"While we are far from being able to quantify it, we believe Deep Life has an important impact on global biogeochemical cycles and chemical equilibria in habitable rocks. Deep Life plays a role in aquifer quality, for example, or carbon capture and storage (CCS). Unfortunately, the deep biosphere is very poorly considered in engineering operations carried out in the subsurface. We recently demonstrated the high reactivity of deep biota to CO2 injections (CCS), which ultimately led to the bioclogging of the injection well, and surrounding reservoir," adds Benedicte Menez, Institut de Physique du Globe de Paris, France.

Source: Deep Carbon Observatory [December 10, 2018]

Researchers discover information about a gene that helps define us as humans

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University of Otago researchers have discovered information about a gene that sets primates—great apes and humans—apart from other mammals, through the study of a rare developmental brain disorder.

Researchers discover information about a gene that helps define us as humans
Brain organoids, or "mini-brains" growing in culture [Credit: Dr Adam O'Neill]
Dr. Adam O'Neill carried out the research as part of his Ph.D. at the University of Otago, under the supervision of Professor Stephen Robertson, discovering that the PLEKHG6 gene has qualities that drives aspects of brain development differently in primates compared to other species.

"Broadly speaking, this gene can be thought of as one of the genetic factors that make us human in a neurological sense," Dr. O'Neill who now works in the Department of Physiological Genomics at Ludwig Maximilian Universität in Munich, Germany, explains.

Professor Robertson says the research, just published in international journal Cell Reports, aimed to address the idea that there must be genes that humans have that have made our brains bigger and better functioning in some respects than other animals. However, that increased complexity could come at a cost, potentially predisposing humans to the development of a whole suite of neurological or psychiatric conditions.


"Such genes have been hard to find, but using an approach where we studied children with a certain brain malformation called periventricular nodular heterotopia, we found a 'damaged' genomic element in a child that had the attributes of such a primate specific genetic factor," he explains. In this particular condition a subset of neurons in the developing brain fail to take up their correct position resulting in a variety of symptoms including epilepsy and delayed development.

Dr. O'Neill and research collaborators from Max Planck Institute of Psychiatry, Germany, then set forth to test the point that the gene drives aspects of brain development that are unique to primates. Some amazing data was found using a novel approach through studying human "mini-brains" in culture. It is now possible to take a skin cell and transform it using a set of genetic tricks, so that it can be triggered to form a tiny brain-like structure in culture in the lab.

Their results showed that the particular genetic change that disabled a component of this gene (PLEKHG6) altered its ability to support the growth and proliferation of specialised stem cells in the developing brain. In addition, some of these cells also failed to migrate to their correct position in the growing "mini-brain" during the first few weeks of brain development.


Professor Robertson says it has been known for a while that these stem cells behave differently between primates/humans and other animals, but understanding what genes regulate these differences has been a mystery.

"Adam's achievement has been to show that this particular component of the PLEKHG6 gene is one such regulator that humans have 'acquired' very recently in their evolution to make their brains 'exceptional'."

Dr. O'Neill says there are very few genetic elements that are primate specific in our genome, so this discovery adds to a very short list of genetic factors that, at least in one sense, make us human.

"Such an understanding positions us to better understand how a brain builds itself- knowledge that will add to our ability to design strategies to repair the damaged brain, especially early in infancy where there are still lots of stem cells around," Dr. O'Neill says.


The work also helps provide more information about the list of genes that are altered to cause this particular type of brain malformation.

"Personally, I also think it does underscore how it is very subtle nuanced differences that separate us from other animals. Our anthropocentrism could be a whole lot more humble," Dr. O'Neill says.

Source: University of Otago [December 06, 2018]

Double the stress slows down evolution

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Like other organisms, bacteria constantly have to fight to survive in hostile living conditions. Together with colleagues in Finland, researchers at the Max Planck Institute for Evolutionary Biology in Plön have discovered that bacteria adapt to their environment more slowly and less efficiently as soon as they are exposed to two stress factors rather than one. This is due to mutations in different genes. The slower rate of evolution led to smaller population sizes. This means that evolution can take divergent paths if an organism is exposed to several stress factors.

Double the stress slows down evolution
The single-cell organism Tetrahymena thermophila (green) with its bacterial prey (purple)
[Credit: Matti Jalasvuori]
Bacteria rarely live alone; they are usually part of a community of species that is exposed to various stress factors. They can often react to these factors by adapting to new environmental conditions with astonishing speed. Antibiotics that enter soil and water via waste water and accumulate there in low concentrations can trigger the evolution of resistance in bacteria – even though these concentrations are so low that they inhibit bacterial growth only slightly or not at all. However, bacteria do not only have to fight antibiotics; they also have to deal with predators. This is why they often grow in large colonies that cannot be consumed by predatory organisms.


Typically, scientists investigate the effects that a single stress factor has on an organism. Researchers at the Max Planck Institute for Evolutionary Biology in Plön and the Universities of Helsinki and Jyväskylä, Finland, have now investigated the question of how microorganisms behave when they are confronted with more than one stress factor. "We simulated natural environmental conditions in the lab and exposed bacteria to both predators and antibiotics. This allows us to estimate how likely it is to find evolution of resistance to antibiotics outdoors," explains study leader Lutz Becks.

Antibiotics and predators

In the scientists' laboratory, the bacterium Pseudomonas fluorescence had to cope with both antibiotics and the predatory single-cell organism Tetrahymena thermophila. After just a short time, the team of researchers noticed that the bacterial population was changing: the bacteria were much slower and less effective in developing resistance and protecting themselves from being consumed than others of the species that were only exposed to one of these factors. Moreover, resistance against the antibiotic was much less common. "The bacteria were clearly unable to optimize both attributes at the same time," says Becks.


In the next step, the scientists analysed the genetic basis of these adaptations. Their results show that mutations for improved protection from predators appear in the same numbers and at the same places in the bacterial genome if only the predatory ciliates are present. The same applies to mutations that cause resistance to antibiotics. However, other mutations occur as soon as both stress factors influence the bacteria and the bacteria have to fight both predators and antibiotics. This causes both the bacteria's protection against predators and resistance to antibiotics to evolve more slowly and be less efficient.

Because the bacteria are less able to protect themselves from predators if they are confronted by the predatory ciliates and antibiotics simultaneously, their numbers are fewer than when they only have to defend themselves from predators. Several stress factors therefore appear to have a strong influence on whether and how often resistance to antibiotics develops and how large the population of bacteria can become.


"Microbial populations – whether in a lake or in the gut – are complex communities in which many species have to compete for resources. The various stress factors to which microbes are exposed have an enormous effect on their evolution and survival rate. It will take some time until we fully understand the interaction of all these factors and the influence of antibiotics and pesticides," explains Becks.

The study is published in Nature Ecology & Evolution.

Source: Max Planck Society [December 06, 2018]

Parrot genome analysis reveals insights into longevity, cognition

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Parrots are famously talkative, and a blue-fronted Amazon parrot named Moises - or at least its genome - is telling scientists volumes about the longevity and highly developed cognitive abilities that give parrots so much in common with humans. Perhaps someday, it will also provide clues about how parrots learn to vocalize so well.

Parrot genome analysis reveals insights into longevity, cognition
This photograph shows an Amazona aestiva taking care of the nest in Pantanal
[Credit: Glaucia Seixas]
Morgan Wirthlin, a BrainHub post-doctoral fellow in Carnegie Mellon University's Computational Biology Department and first author of a report to appear in the journal Current Biology, said she and her colleagues sequenced the genome of the blue-fronted Amazon and used it to perform the first comparative study of parrot genomes.


By comparing the blue-fronted Amazon with 30 other long- and short-lived birds -- including four additional parrot species -- she and colleagues at Oregon Health and Science University (OHSU), the Federal University of Rio de Janeiro and other entities identified a suite of genes previously not known to play a role in longevity that deserve further study. They also identified genes associated with longevity in fruit flies and worms.

"In many cases, this is the first time we've connected those genes to longevity in vertebrates," she said.

Parrot genome analysis reveals insights into longevity, cognition
This photograph shows Amazona aestiva chicks in Pantanal
[Credit: Glaucia Seixas]
Wirthlin, who began the study while a Ph.D. student in behavioral neuroscience at OHSU, said parrots are known to live up to 90 years in captivity -- a lifespan that would be equivalent to hundreds of years for humans. The genes associated with longevity include telomerase, responsible for DNA repair of telomeres (the ends of chromosomes), which are known to shorten with age. Changes in these DNA repair genes can potentially turn cells malignant. The researchers have found evidence that changes in the DNA repair genes of long-lived birds appear to be balanced with changes in genes that control cell proliferation and cancer.


The researchers also discovered changes in gene-regulating regions of the genome -- which seem to be parrot-specific -- that were situated near genes associated with neural development. Those same genes are also linked with cognitive abilities in humans, suggesting that both humans and parrots evolved similar methods for developing higher cognitive abilities.

Parrot genome analysis reveals insights into longevity, cognition
This photograph shows an Amazona aestiva taking care of the nest in Pantanal
[Credit: Glaucia Seixas]
"Unfortunately, we didn't find as many speech-related changes as I had hoped," said Wirthlin, whose research is focused on the evolution of vocal behaviors, including speech. Animals that learn songs or speech are relatively rare -- parrots, hummingbirds, songbirds, whales, dolphins, seals and bats -- which makes them particularly interesting to scientists, such as Wirthlin, who hope to gain a better understanding of how humans evolved this capacity.


"If you're just analyzing genes, you hit the end of the road pretty quickly," she said. That's because learned speech behaviors are thought be more of a function of gene regulation than of changes in genes themselves. Doing comparative studies of these "non-coding" regulatory regions, she added, is difficult, but she and Andreas Pfenning, assistant professor of computational biology, are working on the computational and experimental techniques that may someday reveal more of their secrets.

Author: Byron Spice | Source: Carnegie Mellon University [December 06, 2018]

Sea invertebrate sheds light on evolution of human blood, immune systems

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Botryllus schlosseri, a marine invertebrate that lives in underwater colonies resembling fuzzy pinheads clinging to rocks, has a blood-forming system with uncanny similarities to that of humans, according to scientists at Stanford University.

Sea invertebrate sheds light on evolution of human blood, immune systems
Under the microscope, a Botryllus colony looks like a bouquet of flowers, although in reality each “petal”
is a separate organism with its own heart, gills, digestive system, brain and blood cells
[Credit: Stanford Hopkins Marine Station]
In a study published in Nature, the researchers report that these lowly sea creatures may provide a way to understand our own blood-forming system, improve our immune function and find new immune-associated tools for biological discovery.

"The mammalian and Botryllus blood-forming systems also share hundreds of homologous genes, even though the two species are separated by over 500 million years of evolution," said former postdoctoral scholar Benyamin Rosental, PhD.


Rosental shares lead authorship of the study with graduate student Mark Kowarsky. The senior authors are Irving Weissman, MD, the Virginia and D.K. Ludwig Professor for Clinical Innovation in Cancer Research and professor of pathology and of developmental biology; Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics; and senior research scientist Ayelet Voskoboynik, PhD.

The researchers isolated the Botryllus stem cells that are the foundation of its blood and immune system, as well as the progenitor cells they make on their way to becoming adult blood and immune cells. "Out of all the invertebrates, the Botryllus blood stem cells and progenitors are the most similar to vertebrate blood cells, so it is possible, if not likely, that they are the 'missing link' between vertebrates and invertebrates," said Weissman, who also directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center at Stanford.

Odd characteristics

Botryllus is an organism with many odd characteristics. It lives part of its life as a free-swimming chordate "tadpole" -- an animal without vertebrae but with a spinal bundle called a notochord. Then it attaches itself to a rock, undergoes metamorphosis to lose its notochord, tail, body muscles and one of its two brains, and settles down to live in colonies with other Botryllus organisms on the subtidal surface.

Sea invertebrate sheds light on evolution of human blood, immune systems
The separate Botryllus organisms in the colony share a common blood supply,
and even exchange cells [Credit: Stanford Hopkins Marine Station]
Under the microscope, a Botryllus colony looks like a bouquet of flowers, although in reality each "petal" is a separate organism with its own heart, gills, digestive system, brain and blood cells. The separate Botryllus organisms in the colony share a common blood supply, and even exchange cells. This blood sharing allows stem cells for sperm and eggs and stem cells for body tissues to be shared throughout the growing colony.


The researchers showed that there are close parallels between the blood systems in Botryllus and in mammals. They found that Botryllus has a sort of incubator of specialized cells, called a niche, that holds and supports blood stem cells and is a lot like the blood stem cell niche in mammalian bone marrow. They also found that Botryllus blood stem cells will find their own way from blood vessels to the niche, exactly as they do in mammals. And they found 327 genes involved in blood cell formation in Botryllus that are similar to genes involved in blood formation in mammals.

Previously, researchers in the Weissman lab showed that a single variant of a gene called BHF regulated whether separate Botryllus organisms would send out blood vessels from their own bodies and merge with adjacent individuals, or undergo an immune rejection, preventing blood cell exchanges. The new study identifies how BHF regulates whether organisms fuse together in the colony: If the protein produced by the gene is recognized as compatible by the other colony, it prevents the activation of a rejection process that is similar to the way that the human immune system's natural killer cells attacks tissues that are not "self."

An excellent model

The discovery of such strong parallels between the two systems offers researchers an excellent model for studying many biological phenomena in mammals, the researchers said. "Blood stem cells in mammals are hard to find and, when found, it's very hard to follow what is going on in the blood stem cell niche," Voskoboynik said. "Botryllus is a translucent organism, so we can easily spot the niche and visually follow the migration of each type of cell from one part of their body to the other."


It's also easy to observe how the cells in individual organisms interact when one mounts an immune attack against the other, or the two individuals fuse blood vessels. This could provide scientists with a better understanding of why an organism accepts or rejects foreign cells, knowledge that could give insights into organ transplant acceptance and rejection, Voskoboynik said.

"With its primitive but effective immune system, Botryllus may also give us insights into how we can boost our own immune responses to pathogens and cancer," Voskoboynik said. "But in addition to any practical benefits this research may produce, we are delighted to explore this important guidepost on the path to understanding the evolution of vertebrates, and of their blood-forming and immune systems. Isn't that what curiosity-driven science is supposed to do?"

Author: Christopher Vaughan | Source: Stanford Medicine [December 05, 2018]

30 years of experimental evolution results in a new sex chromosome

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On 3 December 2018, the laboratory of Professor Axel Meyer, University of Konstanz published new findings of an experimental evolutionary project that ran for 30 years on the genomic mechanisms of sex determination in swordtail fish in the journal Nature Communications. Dr Paolo Franchini, evolutionary biologist and Junior Research Group Leader at the University of Konstanz is the lead author of this collaboration with the laboratory of Professor Manfred Schartl of the University of Würzburg

30 years of experimental evolution results in a new sex chromosome
Xiphophorus maculatus hellerii [Credit: Manfred Schartl/Paolo Franchini]
The diversity of sex determination systems is remarkably diverse among fishes compared to mammals that all have a stereotypic XX, XY sex-chromosomal mechanism to determine sex. Why and how the genomic mechanisms and the evolutionary causes behind such diversity in sex determination in fish are so variable remained unknown.

Evolutionary biologist Dr Paolo Franchini with his collaborators has now been able to describe such a mechanism and its exact function in this study entitled "Long-term experimental hybridisation results in the evolution of a new sex chromosome in swordtail fish".

Professor Manfred Schartl, Head of the Department for Physiological Chemistry at the Biocenter of the University of Würzburg, initiated this experiment that included hybridisation with backcrossing by two Xiphophorus fish species with different sex chromosome systems three decades ago. Hybrid origins of species, the result of the crossing of two genetically different species, are found frequently in fish populations.

"What we know from the study of these systems in natural habitats is that hybridisation is a crucial mechanism for the evolution of new species", explains Paolo Franchini. In the experiment the researchers could study the effects of hybridisation on the genomic mechanism of sex-determination.


Determining the sex of these fish is easy: as its name suggests, the male swordtail fish has a sword-like elongated caudal fin; the female, on the other hand, is rounder and fuller and does not have a swordtail. In this long-term laboratory study the effects of hybridisation that is thought to have resulted in at least two swordtail species in nature on the genome and the mechanisms that determine sex could be studied in detail.

In an experimental design that makes it possible to track crossings of more than 100 generations over more than 30 years, a female Xiphophorus maculatus was crossed repeatedly with a male Xiphophorus hellerii.

These two species have different sex chromosome systems. In further steps, the new hybrid fish originating from the cross was backcrossed again with the male species, and this design was repeated for more than 100 generations.

Paolo Franchini explains further: "We found out that introgression - the movement of genetic material from one species to another - and the selection of pigmentation phenotypes results in the retention of an unexpectedly large maternally derived genomic region."


During the hybridisation process, the sex-determining region on the X chromosome of one parent was transferred to an autosome of the hybrid fish. This transfer led to the evolution of a completely new sex chromosome.

"Our results show above all the complexity of factors that contribute to patterns observed in hybrid genomes including such fundamental issues such as sex determination", summarises Paolo Franchini. The work proves that hybridisation can catalyse the rapid evolution of a new sex chromosome and thus makes an essential contribution to an experiment launched more than 30 years ago.

Source: University of Konstanz [December 05, 2018]

Enhancing our vision of the past

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An international group of scientists led by researchers from the University of Bristol have advanced our understanding of how ancient animals saw the world by combining the study of fossils and genetics.

Enhancing our vision of the past
A fossil trilobite with its complex eye. These ancient animals were inferred to have minimally possessed four opsins,
like many modern arthropods, and should have therefore been able to see colours
[Credit: University of Bristol]
Ancestors of insects and crustaceans that lived more than 500 million years ago in the Cambrian period were some of the earliest active predators, but not much is known about how their eyes were adapted for hunting.

Work published in the Proceedings of the Royal Society B suggests that when fossil and genetic data are assessed in tandem, previously inaccessible and exciting conclusions about long dead species can be made.

By examining the morphological characteristics of fossils' eyes, alongside the genetic visual pigment clues, a cross-disciplinary team led by a collaboration between the University of Bristol's Davide Pisani, Professor of Phylogenomics in the School of Earth Sciences and Nicholas Roberts, Professor of Sensory Ecology in the School of Biological Sciences, were able to find that ancient predators with more complex eyes are likely to have seen in colour.


Professor Pisani remarked: "Being able to combine fossil and genetic data in this way is a really exciting frontier of modern palaeontological and biological research. Vision is key to many animals' behaviour and ecology, and understanding how extinct animals perceived their environment will help enormously to clarify how they evolved."

By calculating the time of emergence of different visual pigments, and then comparing them to the inferred age of origin of key fossil lineages, the researchers were able to work out the number of pigments likely to have been possessed by different fossil species. They found that fossil animals with more complex eyes appeared to have more visual pigments, and that the great predators of the Cambrian period may have been able to see in colour.

Dr James Fleming, Professor Pisani and Roberts' former PhD student, explained: "Animal genomes and therefore opsin genes (constituting the base of different visual pigments) evolve by processes of gene duplication. The opsin and the pigment that existed before the duplication is like a parent, and the two new opsins (and pigments) that emerge from the duplication process are like children on a family tree.

"We calculated the birth dates of these children and this allowed understanding of what the ancient world must have seemed like to the animals that occupied it. We found that while some of the fossils we considered had only one pigment and were monochromat, i.e. they saw the world as if looking into a black and white TV, forms with more complex eyes, like iconic trilobites, had many pigments and most likely saw their world in colours."


The combinations of complex eyes and multiple kinds of visual pigments are what allows animals to distinguish between different objects based on colour alone - what we know as colour vision.

Professor Roberts commented: "It is remarkable to see how in only a very few million years the view those animals' had of their world changed from greys to the colourful world we see today."

The project involved scientists from all across the world - from the UK as well as Denmark, Italy, Korea and Japan, where Dr Fleming has now moved to work as a postdoctoral researcher. Each of them brought their own specialities to this multidisciplinary work, providing expertise in genetics, vision, taxonomy and palaeontology.

Source: University of Bristol [December 04, 2018]

Life has a new ingredient

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Our prehistoric Earth, bombarded with asteroids and lightening, rife with bubbling geothermal pools, may not seem hospitable today. But somewhere in the chemical chaos of our early planet, life did form. How? For decades, scientists have attempted to create miniature replicas of infant Earth in the lab. There, they hunt for the primordial ingredients that created the essential building blocks for life.

Life has a new ingredient
Somewhere in the hostile environment of early Earth, life was born
[Credit: Harvard University]
It's attractive to chase our origin story. But this pursuit can bring more than just thrill. Knowledge of how Earth built its first cells could inform our search for extraterrestrial life. If we identify the ingredients and environment required to spark spontaneous life, we could search for similar conditions on planets across our universe.

Today, much of the origin-of-life research focuses on one specific building block: RNA. While some scientists believe that life formed from simpler molecules and only later evolved RNA, others look for evidence to prove (or disprove) that RNA formed first. A complex but versatile molecule, RNA stores and transmits genetic information and helps synthesize proteins, making it a capable candidate for the backbone of the first cells.


To verify this "RNA World Hypothesis," researchers face two challenges. First, they need to identify which ingredients reacted to create RNA's four nucleotides--adenine, guanine, cytosine, and uracil (A, G, C, and U). And, second, they need to determine how RNA stored and copied genetic information in order to replicate itself.

So far, scientists have made significant progress finding precursors to C and U. But A and G remain elusive. Now, in a paper published in the Proceedings of the National Academy of Sciences, Jack W. Szostak, Professor of Chemistry and Chemical Biology at Harvard University, along with first-author and graduate student Seohyun (Chris) Kim suggest that RNA could have started with a different set of nucleotide bases. In place of guanine, RNA could have relied on a surrogate--inosine.


"Our study suggests that the earliest forms of life (with A, U, C, and I) may have arisen from a different set of nucleobases than those found in modern life (A, U, C, and G)," said Kim. How did he and his team arrive at this conclusion? Lab attempts to craft A and G, purine-based nucleotides, produced too many undesired side products. Recently, however, researchers discovered a way to make versions of adenosine and inosine--8-oxo-adenosine and 8-oxo-inosine--from materials available on primeval Earth. So, Kim and his colleagues set out to investigate whether RNA constructed with these analogs could replicate efficiently.

But, the substitutes failed to perform. Like a cake baked with honey instead of sugar, the final product may look and taste similar, but it doesn't function as well. The honey-cake burns and drowns in liquid. The 8-oxo-purine RNA still performs, but it loses both the speed and accuracy needed to copy itself. If it replicates too slowly, it falls apart before completing the process. If it makes too many errors, it cannot serve as a faithful tool for propagation and evolution.


Despite their inadequate performance, the 8-oxo-purines brought an unexpected surprise. As part of the test, the team compared 8-oxo-inosine's abilities against a control, inosine. Unlike its 8-oxo counterpart, inosine enabled RNA to replicate with high speed and few errors. It "turns out to exhibit reasonable rates and fidelities in RNA copying reactions," the team concluded. "We propose that inosine could have served as a surrogate for guanosine in the early emergence of life."

Szostak and Kim's discovery could help substantiate the RNA world hypothesis. In time, their work might confirm RNA's primary role in our origin story. Or, scientists might find that early Earth offered multiple paths for life to grow. Eventually, armed with this knowledge, scientists could identify other planets that have the essential ingredients and determine whether we share this universe or are, indeed, alone.

Source: Harvard University [December 03, 2018]

First jellyfish genome reveals ancient beginnings of complex body plan

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Jellyfish undergo an amazing metamorphosis, from tiny polyps growing on the seafloor to swimming medusae with stinging tentacles. This shape-shifting has served them well, shepherding jellyfish through more than 500 million years of mass extinctions on Earth.

First jellyfish genome reveals ancient beginnings of complex body plan
Jellyfish are an ancient and successful group of animals. An in-depth look at the genome of the moon jelly, Aurita
aurelia, shows that early jellyfish likely repurposed an existing set of genes to transition between polyp
and swimming life stages [Credit: Alexander Vasenin/WikiCommons]
"Whatever they're doing has really worked for them," said David Gold, an assistant professor of paleobiology in the UC Davis College of Letters and Science.

The first in-depth look at the genome of a jellyfish -- the moon jelly Aurelia aurita -- reveals the origins of this successful survival strategy. The Aurelia genome, published online in the journal Nature Ecology and Evolution, indicates early jellyfish recycled existing genes to morph from polyp to medusa. The results suggest animals can radiate into new niches and forms fairly easily.


"These findings provide further evidence that evolution doesn't necessarily make the genetic code more complex," said Gold, a lead researcher on the genome study. "Jellyfish can build a big, complex life history using many of the same genes found in simpler animals."

The research team was led equally by Gold, who performed much of the work as a postdoctoral fellow at the California Institute of Technology, and by Takeo Katsuki, a project scientist at the Kavli Institute for Brain and Mind at UC San Diego.

The genome: a multi-use tool

Jellyfish come from one of the oldest branches on the animal family tree, the phylum Cnidaria, which includes corals and anemones. Jellyfish were probably the first muscle-powered swimmers in the open ocean. They appeared in the late Precambrian Era, a period of major geologic and ecological changes that preceded the Cambrian explosion of animal life.


At some point in their evolution, jellyfish gained the ability to transition from a stationary polyp to a swimming medusa. The transition involves major changes in the jellyfish nervous system, muscles and weaponry, aka the stinging cells called cnidocytes. To accomplish this, the medusa life stage often co-opts existing developmental gene networks and cell types present in polyps, the researchers found. In addition, Aurelia appears to pattern its different life stages using many of the same genes found in animals such as fruit flies and humans, the study reports. (all of these animals share a common ancestor, albeit an ancient one.)

There is a second, more controversial explanation for what the scientists found in the jellyfish genome. Perhaps the similarities between the moon jellyfish genome and "higher" animals demonstrates that the Cnidaria originally had a medusa life stage, which animals like corals and sea anemones lost.


"Our results can't distinguish between these two scenarios," said Gold. If the second hypothesis turns out to be correct, "Swimming, carnivorous animals may be even older than we think." In addition to questions of evolution, the Aurelia genome will prove valuable in many other areas of biology, Gold said. Aurelia is an important model for studying the development and function of nervous systems, and can offer insights into animal wound healing and regeneration. Moon jellies are also a major culprit in environmentally and economically damaging jellyfish blooms, which are becoming more common. For example, giant swarms of moon jellies have clogged water-intake pipes, forcing the shutdown of nuclear plants in Florida and Sweden. An improved understanding of Aurelia genetics could offer new ideas for controlling the blooms.

"In many ways, the ancient oceans in the late Precambrian are very much like what the modern oceans will look like in the near future," Gold said "meaning studying how jellyfish evolved in the past can tell us about their potential impact on the future."

Source: University of California - Davis [December 03, 2018]

Effort clarifies major branch of insect tree of life

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The insects known as Hemiptera are not a particularly glamorous bunch. This group includes stink bugs, bed bugs, litter bugs, scale insects and aphids. Their closest relatives are thrips, bark lice and parasitic lice. But with a massive number of species, two-thirds of which are still unknown to science, these insects together make up one of the twiggiest branches of the tree of life.

Effort clarifies major branch of insect tree of life
Philagra, a Chinese spittlebug [Credit: Christopher Dietrich]
A new study published in the Proceedings of the National Academy of Sciences collected a vast amount of molecular data on these insects and used the information to help tease out their family relationships and evolutionary history. The findings - and the data, which are now publicly available - will aid future research into some of the most abundant and economically important insects on the planet, the researchers said.

"There are 120,000 known species in this group, which is maybe a third of what's actually out there," said Illinois Natural History Survey entomologist Christopher Dietrich, who led the study with INHS ornithologist Kevin Johnson. "To put that in perspective, that's more than all the vertebrates combined. It's a massively diverse group. They cover the planet. They're in every habitat."


Many of these insects feed on plants and animals and can be seen as pests, Dietrich said. But they also provide food for birds, insectivorous mammals, reptiles, amphibians and other predacious insects.

"Many of them form the first link of the food chain, converting plant material into protein that can be used by other animals," he said.

Among this group are many, like aphids and planthoppers, that afflict crops; others, such as body lice and certain assassin bugs, transmit disease, Dietrich said.

Effort clarifies major branch of insect tree of life
Bird louse [Credit: Stephany Virrueta Herrera]
To sort out these insects' family relationships and history, the researchers analyzed nearly 2,400 protein-coding genes, their expression in the form of messenger RNA and the resulting amino-acid sequences. It was a massive effort involving collaborators in China, Europe, Japan and across the United States.

"We wanted to use newer sequencing technologies to address how all these major groups of hemipteroid insects related to each other," Johnson said. "This is probably one of the largest data sets in existence for insects."


The effort yielded several key findings. The most interesting of these had to do with the development of special mouthparts in some members of this group, the researchers said.

"The earliest, most primitive insects just had a pair of mandibles to chew, like ants do," Dietrich said. "But some groups went off in a different direction."

For those, the mandibles gradually evolved into sturdy narrow tubes that could pierce things and suck out the juices. "It was a major shift in feeding strategy," Dietrich said. "All the insects to this point had just been chomping on things."

Effort clarifies major branch of insect tree of life
Assassin bug of the family Reduviidae [Credit: Rachel Skinner]
The team's molecular divergence estimate revealed that the evolution of piercing and sucking mouthparts likely occurred more than 350 million years ago. Similar mouthparts evolved independently in parasitic lice and other insects with the trait, such as mosquitoes.

"According to the fossil record, this group became the dominant group of insects on Earth in the Permian, 300 million years ago to 250 million years ago," Dietrich said. "But at the end of the Permian they underwent a mass extinction, which was worse than the one that killed off the dinosaurs a couple hundred million years later."


Eventually, the Hemiptera, along with the orders representing thrips and lice, were eclipsed by another group of insects, the Holometabola, which undergo complete metamorphosis and are even more diverse. Holometabola include butterflies, moths, ants, bees, flies and beetles.

Though more robust than other genetic studies of this group of insects, the new analysis has not fully resolved the relationship between the order that includes bark lice and parasitic lice, and the hemiptera and thrips, which likely belong to the same superorder, the researchers said. But the study sets the stage for future work, and an improved understanding of how some of the less charismatic, but ecologically essential, insects evolved.

Source: University of Illinois at Urbana-Champaign [November 26, 2018]

How ancient viruses got cannabis high

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THC and CBD, bioactive substances produced by cannabis and sought by medical patients and recreational users, sprung to life thanks to ancient colonization of the plant's genome by viruses, U of T researchers have found.

How ancient viruses got cannabis high
Modern day hemp and marijuana evolved distinct chemistry thanks to ancient viruses that colonized
the ancestral cannabis genome millions of years ago [Credit: Michael Fischer]
The finding is only one of the insights revealed by the long-awaited cannabis genome map detailing gene arrangement on the chromosomes, published recently in the journal Genome Research. Among other revelations are discovery of a gene responsible for the production of cannabichromene, or CBC, a lesser known cannabinoid, as the active substances in cannabis are known, and new insights into how strain potency is determined.

"The chromosome map is an important foundational resource for further research which, despite cannabis' widespread use, has lagged behind other crops due to restrictive legislation," says Tim Hughes, a professor in the Donnelly Centre for Cellular and Biomolecular Research and co-leader of the study. Hughes is also a professor in the Department of Molecular Genetics and Senior Fellow at the Canadian Institute for Advancement of Research.

The researchers expect the map will speed up breeding efforts to create new strains with desired medical properties as well as varieties that can be grown more sustainably, or with increased resistance to diseases and pests.


The study was a three-part collaboration between Tim Hughes' team and those of Jonathan Page, of Aurora Cannabis and the University of British Columbia , and Harm van Bakel, of the Icahn School of Medicine at Mt Sinai in New York.

Hughes, Page and van Bakel first got together in 2011 when they released the first draft of cannabis genome which was too fragmented to reveal gene position on chromosomes.

The new map reveals how hemp and marijuana, which belong to the same species Cannabis sativa, evolved as separate strains with distinct chemical properties. Cannabis plants grown for drug use ("marijuana") are abundant in psychoactive tetrahydrocannabinol, or THC, whereas hemp produces cannabidiol, or CBD, popular of late for its medicinal potential. Some people use CBD to relieve pain and it is also being tested as a treatment for epilepsy, schizophrenia and Alzheimer's.


The enzymes making THC and CBD are encoded by THCA and CBDA synthase genes, respectively. Both are found on chromosome 6 of the ten chromosomes the cannabis genome is packaged into. There, the enzyme genes are surrounded by vast swathes of garbled DNA which came from viruses that colonized the genome millions of years ago. This viral DNA, or retroelements as it is known, made copies of itself that spread across the genome by jumping into other sites in the host cell's DNA.

"Plant genomes can contain millions of retroelement copies," says van Bakel, an assistant professor in the Icahn Institute for Data Science and Genomic Technology in New York and in the department of Genetics and Genome Sciences. "This means that linking genes on chromosomes is analogous to assembling a huge puzzle where three quarters of the pieces are nearly the same color. The combination of a genetic map and PacBio sequencing technology allowed us to increase the size of the puzzle pieces and find enough distinguishing features to facilitate the assembly process and pinpoint the synthase genes."

The researchers believe that gene duplication of the ancestral synthase gene and expanding retroelements drove ancient cannabis to split into chemically distinct types. Humans subsequently selected for plants containing desirable chemistry such as high THC.

The gene sequences for the THCA and CBDA synthases are nearly identical supporting the idea that they come from the same gene which was duplicated millions of years ago. Over time, one or both gene copies became scrambled by invading retroelements, and by evolving separately, they eventually came to produce two different enzymes - CBDA synthase found in hemp (fibre-type), and THCA synthase in drug-type (marijuana).


Because the enzymes are so similar at the DNA level, until this study it was not even clear if they are encoded by separate genes or by two versions of the same gene. Adding to the confusion was the fact that most strains produce both CBD and THC despite breeders' efforts to grow hemp varieties free from the mind-altering THC for users looking to avoid it.

The chromosome map now clearly shows that two distinct genes are at play which should make it possible to separate them during breeding to grow plants without THC.

Some psychoactive effects in medical strains could be coming from CBC, a lesser known cannabinoid that has unusual pharmacology including anti-inflammatory properties. The discovery of the gene responsible for CBC synthesis will make it possible for breeders to tailor its content in future varieties.

"Mainstream science has still not done enough because of research restrictions," says Page, of UBC and Chief Scientific Officer at Aurora, one of Canada's largest producers of medical cannabis. "Legalization and looming ease of research regulation really provide for opportunities for more research to be done. And Canada is leading the way."

Source: University of Toronto [November 26, 2018]