Is this how simple life got complicated?

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(Biomechanism.com) — A new study has created an analog of what researchers think the first multicellular cooperation might have looked like, showing that yeast cells—in an environment that requires them to work for their food—grow and reproduce better in multicellular clumps than singly.

Saccharomyces Cerevisiae cells observed at the microscope.

A team of researchers, led by Harvard professor Andrew Murray, found that cells of brewer’s yeast that clumped together were able more effectively to manipulate and absorb sugars in their environment than were similar cells that lived singly. The experiments showed that in environments where the yeast’s sugar food source is dilute and the number of cells is small, the ability to clump together allowed cells that otherwise would have remained hungry and static to grow and divide.

The work, published August 9 in the online, open access journal PLoS Biology, used the yeast Saccharomyces cerevisiae, which is commonly used in brewing and bread-making and has long been used by scientists as a model organism for understanding single-celled life. Murray and colleagues devised a series of experiments that presented two problems for the yeast cells to solve if they were to take in enough food to grow and divide: the first was how to change their food from an unusable form to a usable form; the second was how to actually take in this food.

The researchers put the yeast in a solution of sucrose—plain old table sugar—which is composed of two simpler sugars, glucose and fructose. Yeast lives on sugar, but the sucrose can’t get through the membrane that surrounds the cell. So the yeast makes an enzyme called invertase to chop the sucrose into glucose and fructose, each of which can enter the cell using gate-keeping molecules, called transporters, that form part of the membrane.

The second problem was how to get the glucose and fructose from the place where they were split apart by invertase to the transporters in the cell membrane. The only way to bridge the gap is through diffusion, an inefficient process. Researchers calculated that once a cell makes invertase and chops the larger sugar down to usable bits, only one sugar molecule in 100 would be captured by the cell that made it.

They also calculated that, working alone, a single yeast cell in a dilute solution of sucrose would never take in enough glucose and fructose to be able to grow and divide. But by cooperating, clumps of yeast in that same solution might have a chance. With several cells in proximity, all releasing invertase to create smaller sugars, these cooperating yeast cells would increase the density of those sugars near the clump, increasing the chances that each cell could take in enough to grow and divide. Sure enough, when the researchers tested these hypotheses on two strains of yeast, they found that the strain which clumped cells together was growing and dividing, while the yeast cells living alone were not.

Murray said the work offers one explanation as to why single-celled organisms might have initially banded together deep in the history of life, although it’s impossible to prove conclusively that this is what happened. “Because there is an advantage to sticking together under these circumstances, and because we know that lots of single-celled organisms make enzymes to liberate goods from their environment, this may be the evolutionary force that led to multicellularity,” Murray said. Although, he continued, “short of inventing time travel and going back several billion years to see if this is how it happened…this is going to remain speculation.”

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Funding: JK is supported by NIH NIGMS award K25GM085806-01, KF is supported by European Research Council Grant 242670, and AM is supported by NIGMS Center for Systems Biology (GM068763). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Citation: Koschwanez JH, Foster KR, Murray AW (2011) Sucrose Utilization in Budding Yeast as a Model for the Origin of Undifferentiated Multicellularity. PLoS Biol 9(8): e1001122. doi:10.1371/journal.pbio.1001122

The machinery for recombination is part of the chromosome structure

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New insights into the biology of germ cells…

(Biomechanism.com) — During the development of gametes, such as egg and sperm cells in humans, chromosomes are broken and rearranged at many positions. Using state of the art technology, the research group of Franz Klein, professor for genetics at the Max F. Perutz Laboratories of the University of Vienna, has analyzed this process at high resolution. The surprising observations regarding the biomechanism of meiosis are now published in the scientific top-journal Cell.

Without meiosis there would be no sexual reproduction, as germ cells have to be generated in this specialized cell division. Meiosis results in daughter cells containing a single, complete set of chromosomes, while body cells contain two sets. During fertilization, when sperm and egg fuse, their sets of chromosomes are combined to form a diploid embryo to close the cycle.

Caption: This is a section of a chromosome with "DNA-break machines." Loops of sister chromatids (blue and turquoise) are linked and held in shape by ring-shaped molecules. The machines are anchored between the DNA-loops at the axis of the chromosome. One of the two machines holds on to a piece of DNA it just has broken. This model only illustrates the principles described in the text above; other details (such as the form of the machines, colors etc.) are symbolic and not to be taken literally. Credit: Illustration: Franz Klein

Enigmatic meiosis

There are 46 chromosomes in every human cell, 23 maternal and 23 paternal ones. When germ cells are produced, one aspect of the reduction in chromosome numbers comes from merging maternal and paternal chromosomes to form a single daughter chromosome – a biomechanism called recombination. “The more we learn about meiosis, the more mysterious it becomes”, says Franz Klein from the Department for Chromosome Biology of the University of Vienna. “It is surprising that maternal and paternal chromosomes find each other at all. Because at the time of interaction all chromosomes have generated a sister and are tightly connected with her like a Siamese twin. Normally, in non-meiotic cells, chromosomes only interact and exchange with the sister chromosome. However, during the development of germ cells, only the exchange between parental chromosomes can guarantee the production of daughter cells with the right number of chromosomes”, explains Klein.

Nano-view of the chromosome

Franz Klein and his research team have analyzed components of the protein machinery, which initiates recombination by DNA-breakage. They created a high resolution map of the chromosomes and marked the interaction sites with those proteins. “Thanks to DNA microarray-technology, we get a resolution in the nanometer range, with insights unimaginable before”, says Klein. The researchers were surprised to find the DNA-breaking machine tightly associated with chromosomal axis regions, instead of being soluble – an observation with far reaching consequences.

Disposable machines

One of the many riddles in meiosis was how breaks on chromosomes impede the occurrence of other breaks in their vicinity. Earlier research had shown that each individual DNA-breakage complex only works a single time. “As we now know that these machines are anchored, we understand why there is preferentially a single break per region. The locally bound machine has fired and other machines can’t get there as they are anchored to other chromosomal regions”, explains Klein.

When chromosomes are out of shape

Healthy chromosomes can form DNA loops, which are, in meiosis, connected by a protein axis. Defective genes can cause chromosomes to lose this shape. “No one could understand why the shape of chromosomes influences the function of the DNA-break machines. Now we know that these machines have to anchor between loops on the chromosome axis. If their loop-environment changes they anchor in different regions or lose functionality altogether”, says Klein.

Hyperactive sister

Sister chromosomes are connected like Siamese twins along the chromosome axis, where the DNA-break machines are anchored. It was very mysterious, how the sister chromosome is prevented to take part in the repair of DNA breaks during meiosis, despite being so close to the damage. A special feature of meiosis is the formation of a zone along the chromosome axis that inhibits recombination.

Franz Klein concludes: “We think that the DNA-break machines are anchored at the axis to position the breaks right within the recombination inhibiting zone. This may attract the sister chromosome loop, which remains trapped in the recombination inhibiting zone by one of the two ends flanking the break, while the second end docks off to form a search tentacle for finding the paternal chromosome. We have evidence for many details of this scenario – but most importantly, the inhibition of the involvement of the sister breaks down, if the anchoring of the DNA-break machines is defective. This indicates that anchoring may be indeed a key mechanism to control the sister. The result of a sister, hyperactive for DNA-break repair in meiosis is the death or severe impairment of the developing embryo.”

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Funding

The published work was conducted within the framework of the Special Research Program F34-”Dynamic Chromosomes” of the FWF. Seven research groups of the Max F. Perutz Laboratories (MFPL) and the Institute of Molecular Pathology (IMP) collaborate in this research program to unravel questions of chromosome biology. Coordination: Franz Klein and Jan Michael Peters, this year’s Wittgenstein awardee.

Study shows an ancient crop ‘flaxseed’ is effective in protecting against a 21st century hazard

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(Biomechanism.com) — A diet of flaxseed shows protective effects against radiation in animal models.

Flax has been part of human history for well over 30,000 years, used for weaving cloth, feeding people and animals, and even making paint. Now, researchers from the Perelman School of Medicine at the University of Pennsylvania have discovered that it might have a new use for the 21st century: protecting healthy tissues and organs from the harmful effects of radiation. In a study just published in BMC Cancer, researchers found that a diet of flaxseed given to mice not only protects lung tissues before exposure to radiation, but can also significantly reduce damage after exposure occurs.

Flax seed is high in fiber, lignans, alpha linolenic acid, omega-3 fat, and is also a key player in the fight against cancer, particularly breast and colon cancer. Photo: Wikipedia

“There are only a handful of potential mitigators of radiation effect, and none of them is nearly ready for the clinic,” says the principal investigator Melpo Christofidou-Solomidou, PhD, research associate professor of Medicine, Pulmonary, Allergy and Critical Care Division. “Our current study demonstrates that dietary flaxseed, already known for its strong antioxidant and anti-inflammatory properties, works as both a mitigator and protector against radiation pneumonopathy.”

In several separate experiments, the researchers fed one group of mice a diet supplemented with 10 percent flaxseed, either three weeks before a dose of X-ray radiation to the thorax or two, four, or six weeks after radiation exposure. A control group subjected to the same radiation dose was given the same diet but receiving an isocaloric control diet without the flaxseed supplement. After four months, only 40 percent of the irradiated control group survived, compared to 70 to 88 percent of the irradiated flaxseed-fed animals. Various studies of blood, fluids, and tissues were conducted.

Dr. Christofidou-Solomidou and her colleagues found that the flaxseed diet conferred substantial benefits regardless of whether it was initiated before or after irradiation. Mice on flaxseed displayed improved survival rates and mitigation of radiation pneumonitis, with increased blood oxygenation levels, higher body weight, lower pro-inflammatory cytokine levels, and greatly reduced pulmonary inflammation and fibrosis.

The latter finding is especially exciting, because while radiation-induced inflammatory damage can be potentially treated with steroidal therapy (in radiotherapy patients for example), lung fibrosis is essentially untreatable. “There’s nothing you can give to patients to prevent fibrosis,” Dr. Christofidou-Solomidou points out. “Once a lung becomes “stiff” from collagen deposition, it’s irreversible. We have discovered that flaxseed not only prevents fibrosis, but it also protects after the onset of radiation damage.”

Dr. Christofidou-Solomidou and her colleagues are focusing further research on the bioactive lignan component of flaxseed, known as SDG (secoisolariciresinol diglucoside), which is believed to confer its potent antioxidant properties. The lignan component also “regulates the transcription of antioxidant enzymes that protect and detoxify carcinogens, free radicals and other damaging agents”, she says.

Flaxseed boasts many other qualities that make it particularly attractive as a radioprotector and mitigator. “Flaxseed is safe, it’s very cheap, it’s readily available, there’s nothing you have to synthesize,” Dr. Christofidou-Solomidou notes. “It can be given orally so it has a very convenient administration route. It can be packaged and manufactured in large quantities. Best of all, you can store it for very long periods of time.” That makes it especially interesting to government officials looking to stockpile radioprotective substances in case of accidental or terrorist-caused radiological disasters.

Co-author Keith Cengel, MD, PhD, assistant professor of Radiation Oncology at Penn, explains that in such cases, “a big issue is the ‘worried well’ — all the folks who probably weren’t exposed but are concerned and want to do something.” Many potential radioprotectors, however, could have risky side effects. Dr. Christofidou-Solomidou adds, “When you give something to 4 or 5 million ‘worried well,’ you have people with preexisting medical conditions. You can’t give just anything to people with heart disease, for example. But this is absolutely safe. In fact, it is known to increase cardiovascular health, a finding shown by another group of Penn investigators a few years ago. It’s loaded with omega-3 fatty acids.”

Along with other researchers at the Perelman School of Medicine, the authors are conducting further pilot studies on the potential of flaxseed for mitigation of lung damage in patients awaiting lung transplants and those undergoing radiation therapy for the treatment of intra-thoracic malignancies.

Dr. Christofidou-Solomidou is even conducting a pilot study for NASA on the benefits of flaxseed for astronauts on extended deep space missions. Lengthy space exploration missions require that the astronauts perform extravehicular activities (EVAs) for repairs, during which they can face exposure to high levels of solar and galactic radiation with the added risk factor of breathing 100 percent oxygen. “Hyperoxia superimposed with radiation could potentially cause some lung damage and some reason to worry for the astronauts,” she says. “We are one of a handful of teams in the US that can study radiation in addition to hyperoxia. So now we’re adding another level of complexity to the one-hit, radiation damage studies; the double-hit model is something novel, nobody has done it before.”

The researchers are already convinced enough to incorporate flaxseed into their own routine. “I actually eat it every morning,” says Dr. Cengel, noting, “The potential health benefits are significant and there is no known toxicity—it just makes good sense to me.”

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The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA) under a grant initiative focused on the development of novel medical countermeasures to prevent or mitigate pulmonary injury or restore function after exposure to ionizing radiation

The “Awesome Power” of Yeast: An Almost Perfect Match

The “Awesome Power” of Yeast: An Almost Perfect Match

Posted by Biomechanism 

(Biomechanism.com)– Yeast has been known and loved by human beings since ancient times. When added to mashed-up wheat, it makes bread rise. When added to squashed grapes, it produces wine. Its warm, slightly fruity smell is the smell of live cells at work. Even a slim package of “active dry” yeast contains roughly 35 billion cells of Saccharomyces cerevisiae (baker’s or brewer’s yeast), and as soon as these cells find food, they produce fermentation bubbles—the bubbles that cause dough to rise or beer to foam.

The 3-D structures of many yeast and mammalian proteins are nearly identical. Here the structure of the yeast actin (yellow) is superimposed on the structure of the mammalian actin, a muscle protein (blue), and fits almost perfectly. Image: Sergey Vorobiev

Yeast is also plentiful. When you eat grapes, you swallow millions of live yeast cells that were feasting on sugar on the grapes’ surface. Yeast is cheap. It’s easy to grow—yeast cells double every 90 minutes when food is available, and billions of them will fit in a few petri dishes.

Not only are these cells alive (until oven heat kills them), they can do almost everything that human cells do to survive: transmit signals from the cell’s surface to its nucleus, manufacture thousands of proteins, create a cellular scaffolding, repair DNA in the nucleus, and so on. And although yeast cannot make tissues and does not have a brain, it is universally recognized as the best model organism for studies of anything that goes on inside a single cell.

Researchers speak glowingly of the “awesome power” of yeast genetics to solve problems in biology. “It’s so easy with yeast!” says Randy Schekman, an HHMI investigator at the University of California, Berkeley. He points out that “genetic surgery has been possible in yeast for 20 years. You can stitch bits of DNA from a normal yeast cell onto a plasmid, the plasmid will carry this DNA into a mutant yeast cell, and the normal yeast gene will replace the mutant one at precisely the right place.”

It’s also very quick. The yeast genome has so few genes—6,000, compared with the estimated 40,000 genes in mice and humans–and the tools for manipulating these genes are so highly developed that yeast experiments can generally be performed in days or weeks. Similar experiments in mice might take years—if they could be done at all.

Another great virtue of yeast is that its genes have very few of the bothersome introns (intervening sequences of DNA) that interrupt the coding sequences of mammalian genes. This makes it “easy to recognize where the genes are in yeast and what their boundaries are, just by looking at the genome sequence,” Pat Brown explains. He notes that approximately 70 percent of the yeast genome codes for protein—a huge amount, compared with only 5 percent of the human genome. (The function of the remaining 95 percent of the human genome is still unknown.)

Despite these differences, large numbers of yeast genes closely resemble those of mice and humans. They also produce nearly identical proteins. “You can generally take a yeast protein and an equivalent human protein and superimpose their 3-D structures, and they will be crystallographically the same,” says David Botstein. In his studies of actin, a protein, Botstein found that “not only is actin conserved [unchanged by evolution] from yeast to humans but most of the proteins that interact with actin in yeast are also conserved, and so are their interactions.”

Philip Hieter of the University of British Columbia in Vancouver, a pioneer of what he calls “comparative genomics,” remembers that when he gave talks about yeast in the 1980s, “there was a lot of skepticism. People didn’t appreciate how similar yeast was to mammals. But the next 10 years showed that all the basic pathways within cells are much more conserved than anybody expected at the time.

So if you examine a new human protein—a protein involved in a human disease, let’s say—and you find that it matches a yeast protein, this brings up the entire biochemical pathway.” For a biomedical scientist, that’s like hitting a jackpot.

Sneaky squid: Why small males have big sperm

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Male squid (Loligo bleekeri) employ different reproductive strategies depending on their body size. Research published in BioMed Central’s open access journal BMC Evolutionary Biology shows that the divergent mating behavior of male squid has resulted in the evolution of different sperm sizes.

Larger male squids strategy resulted in higher paternity rates - but for smaller males, who cannot win a female by fair means, being sneaky gives them a chance of passing on their genes.

Large male squid compete for females by courting them with flashy skin color-change displays. Once a female has chosen her partner they mate in an above and below position so that the male can place his sperm inside the female’s oviduct. He remains with the female until she spawns, ensuring that his sperm fertilize her eggs and that no other males have a chance to mate with her. At the moment a female lays her eggs, small ‘sneaker’ males rush in and mate with her, head to head. These small males place packages of sperm by the female’s mouth in the hope that their sperm have a chance of fertilizing the eggs as they leave the female’s body.

When researchers from London and Japan looked at the sperm produced by small sneaker males and large consort males they discovered that the sperm produced by the sneaker males was larger than that of the consorts. Dr Yoko Iwata from University of Tokyo said, “Sperm size is likely to be an adaptation to fertilization environment, either inside the female or externally, rather than competition between sperm, because the fertility and motility of sneaker and consort sperm were the same.”

Overall, the larger males’ strategy resulted in higher paternity rates – but for smaller males, who cannot win a female by fair means, being sneaky gives them a chance of passing on their genes.

The complete study is available in PDF:  Why small males have big sperm: dimorphic squid sperm linked to alternative mating behaviours.  

Authors: Yoko Iwata, Paul Shaw, Eiji Fujiwara, Kogiku Shiba, Yasutaka Kakiuchi and Noritaka Hirohashi.

Abstract From The Study

Background

Sperm cells are the target of strong sexual selection that may drive changes in sperm structure and function to maximize fertilisation success. Sperm evolution is regarded to be one of the major consequences of sperm competition in polyandrous species, however it can also be driven by adaptation to the environmental conditions at the site of fertilization. Strong stabilizing selection limits intra-specific variation, and therefore polymorphism, among fertile sperm (eusperm). Here we analyzed reproductive morphology differences among males employing characteristic alternative mating behaviours, and so potentially different conditions of sperm competition and fertilization environment, in the squid Loligo bleekeri.

Results

Large consort males transfer smaller (average total length = 73 um) sperm to a female’s internal sperm storage location, inside the oviduct; whereas small sneaker males transfer larger (99 um) sperm to an external location around the seminal receptacle near the mouth. No significant difference in swimming speed was observed between consort and sneaker sperm. Furthermore, sperm precedence in the seminal receptacle was not biased toward longer sperm, suggesting no evidence for large sperm being favoured in competition for space in the sperm storage organ among sneaker males.

Conclusions

Here we report the first case, in the squid Loligo bleekeri, where distinctly dimorphic eusperm are produced by different sized males that employ alternative mating behaviours. Our results found no evidence that the distinct sperm dimorphism was driven by between- and within-tactic sperm competition. We propose that presence of alternative fertilization environments with distinct characteristics (i.e. internal or external), whether or not in combination with the effects of sperm competition, can drive the disruptive evolution of sperm size.

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