Lab yeast make evolutionary leap to multicellularity

IN JUST a few weeks single-celled yeast have evolved into a multicellular organism, complete with division of labour between cells. This suggests that the evolutionary leap to multicellularity may be a surprisingly small hurdle.

 One giant leap for yeastkind 

Multicellularity has evolved at least 20 times since life began, but the last time was about 200 million years ago, leaving few clues to the precise sequence of events. To understand the process better, William Ratcliff and colleagues at the University of Minnesota in St Paul set out to evolve multicellularity in a common unicellular lab organism, brewer's yeast.

Their approach was simple: they grew the yeast in a liquid and once each day gently centrifuged each culture, inoculating the next batch with the yeast that settled out on the bottom of each tube. Just as large sand particles settle faster than tiny silt, groups of cells settle faster than single ones, so the team effectively selected for yeast that clumped together.

Sure enough, within 60 days - about 350 generations - every one of their 10 culture lines had evolved a clumped, "snowflake" form. Crucially, the snowflakes formed not from unrelated cells banding together but from cells that remained connected to one another after division, so that all the cells in a snowflake were genetically identical relatives. This relatedness provides the conditions necessary for individual cells to cooperate for the good of the whole snowflake.

"The key step in the evolution of multicellularity is a shift in the level of selection from unicells to groups. Once that occurs, you can consider the clumps to be primitive multicellular organisms," says Ratcliff.

In some ways, the snowflakes do behave as if they are multicellular. They grow bigger by cell division and when the snowflakes reach a certain size a portion breaks off to form a daughter cell. This "life cycle" is much like the juvenile and adult stages of many multicellular organisms.

After a few hundred further generations of selection, the snowflakes also began to show a rudimentary division of labour. As the snowflakes reach their "adult" size, some cells undergo programmed cell death, providing weak points where daughters can break off. This lets the snowflakes make more offspring while leaving the parent large enough to sink quickly to the base of the tube, ensuring its survival. Snowflake lineages exposed to different evolutionary pressures evolved different levels of cell death. Since it is rarely to the advantage of an individual cell to die, this is a clear case of cooperation for the good of the larger organism. This is a key sign that the snowflakes are evolving as a unit, Ratcliff reported last week at a meeting of the Society for the Study of Evolution in Norman, Oklahoma.

Other researchers familiar with the work were generally enthusiastic. "It really seemed to me to have the elements of the unfolding in real time of a major transition," says Ben Kerr, an evolutionary biologist at the University of Washington in Seattle. "The fact that it happened so quickly was really exciting."

Sceptics, however, point out that many yeast strains naturally form colonies, and that their ancestors were multicellular tens or hundreds of millions of years ago. As a result, they may have retained some evolved mechanisms for cell adhesion and programmed cell death, effectively stacking the deck in favour of Ratcliff's experiment.

"I bet that yeast, having once been multicellular, never lost it completely," says Neil Blackstone, an evolutionary biologist at Northern Illinois University in DeKalb. "I don't think if you took something that had never been multicellular you would get it so quickly."

Even so, much of evolution proceeds by co-opting existing traits for new uses - and that's exactly what Ratcliff's yeast do. "I wouldn't expect these things to all pop up de novo, but for the cell to have many of the elements already present for other reasons," says Kerr.

Ratcliff and his colleagues are planning to address that objection head-on, by doing similar experiments with Chlamydomonas, a single-celled alga that has no multicellular ancestors. They are also continuing their yeast experiments to see whether further division of labour will evolve within the snowflakes. Both approaches offer an unprecedented opportunity to bring experimental rigour to the study of one of the most important leaps in our distant evolutionary past.

Source New Scientist

Cause of hereditary blindness discovered

RUB Medicine: new protein identified.

Initially the occurrence of progressive retinal degeneration - progressive retinal atrophy, in man called retinitis pigmentosa - had been identified in Schapendoes dogs. Retinitis pigmentosa is the most common hereditary disease which causes blindness in humans. The researchers report on their findings, in Human Molecular Genetics.

Genetic test developed Based on the new findings, the researchers from Bochum have developed a genetic test for diagnosis in this breed of dogs that can also be used predictively in breeding. Schapendoes dogs are originally a Dutch breed of herding dog, which is now kept mainly in Holland, Germany, Northern Europe and North America. However, the research results are also potentially significant for people. The scientists are currently investigating whether mutations of the CCDC66 gene could also be responsible for some retinitis pigmentosa patients.

Mouse model: disease progression in months instead of years "Since at the beginning of the work, the importance of the CCDC66 protein in the organism was completely unknown, in collaboration with Dr. Thomas Rülicke (Vienna) and Prof. Dr. Saleh Ibrahim (Lübeck), we developed a mouse model with a defect in the corresponding gene" explained Prof. Epplen. The aim was initially to obtain basic information about the consequences of the CCDC66 deficiency in order to draw conclusions on the physiological function of the protein. "Fortunately, the mice showed exactly the expected defect of slow progressive impaired vision", said Epplen. "Along with Dr. Elisabeth Petrasch-Parwez (RUB) and Prof. Dr. Jan Kremers (Erlangen), we were able to anatomically and functionally study the entire development of the visual defect in the mouse in just a few months, whereas the progress takes years in humans and dogs." In this interdisciplinary project, the researchers have precisely documented and characterised the progress of retinal degeneration. Epplen: "Interestingly, the CCDC66 protein is, for example, only localised in certain structures of the rods".

Studies continue The insights gained from the studies of the working group can now be applied in order to better understand the processes that cause this inherited disorder. The mouse model will be studied further, as the researchers said: "with regard to malfunctions of the brain, but naturally, above all as a prerequisite for future therapeutic trials in retinitis pigmentosa."


Source EurekaAlert!

Magnetic Field Sensed by Gene, Study Shows

A researcher studying how monarch butterflies navigate has picked up a strong hint that people may be able to sense the earth’s magnetic field and use it for orienting themselves. 

Many animals rely on the magnetic field for navigation, and researchers have often wondered if people, too, might be able to detect the field; that might explain how Polynesian navigators can make 3,000-mile journeys under starless skies. But after years of inconclusive experiments, interest in people’s possible magnetic sense has waned.

That may change after an experiment being reported Tuesday by Steven M. Reppert, a neurobiologist at the University of Massachusetts Medical School, and his colleagues Lauren E. Foley and Robert J. Gegear. They have been studying cryptochromes, light-sensitive proteins that help regulate the daily rhythm of the body’s cells, and how they help set the sun compass by which monarchs navigate.

But the butterflies can navigate even when the sun is obscured, so they must have a backup system. Since physical chemists had speculated the cryptochromes might be sensitive to magnetism, Dr. Reppert wondered if the monarch butterfly was using its cryptochromes to sense the earth’s magnetic field. He first studied the laboratory fruit fly, whose genes are much easier to manipulate and showed three years ago that the fly could detect magnetic fields but only when its cryptochrome gene was in good working order.
He then showed that the monarch butterfly’s two cryptochrome genes could each substitute for the fly’s gene in letting it sense magnetic fields, indicating that the butterfly uses the proteins for the same purpose.

One of the monarch’s two cryptochrome genes is similar in its DNA sequence to the human cryptochrome gene. That prompted the idea of seeing whether the human gene, too, could restore magnetic sensing to fruit flies whose own gene had been knocked out. In the journal Nature Communications, Dr. Reppert reports that this is indeed the case. “A reassessment of human magnetosensitivity may be in order,” he and his colleagues write.

The human cryptochrome gene is highly active in the eye, raising the possibility that the magnetic field might in some sense be seen, if the cryptochromes interact with the retina.
Dr. Reppert said the focus on human use of the magnetic field for navigation might be misplaced. Following an idea proposed last year by John B. Phillips of Virginia Tech, he said the primary use of magnetic sensing might be for spatial orientation.

“It could be providing a spherical coordinate system that the animal could use for spatial positioning,” he said.
Dr. Phillips said that Dr. Reppert’s work was of interest but that he had been surprised by an experiment in which Dr. Reppert disrupted the part of the cryptochrome thought to interact with the magnetic field, yet the flies had still detected the magnetism. “It’s 50-50 whether he’s really studying what he thinks he is,” Dr. Phillips said.

Dr. Reppert replied that he had already ruled out the alternative explanation suggested by Dr. Phillips.
But both scientists agreed on the possibilities opened up by the cryptochrome system. Depending on how the proteins are aligned in the eye, insects may perceive objects as being lighter or darker as they orient themselves in relation to the magnetic field, Dr. Phillips said.
In fact, the cryptochrome system might supply a grid imposed on all the landmarks in a visual scene, helping a squirrel find a buried acorn, or a fox integrate its visual scene with what it hears. “This is the fun stage where we are not constrained by many facts,” Dr. Phillips said.

If butterflies, birds and foxes possess such a wonderful system, why would it ever have died out in the human lineage? “It may be that our electromagnetic world is interfering with our ability to do this kind of stuff,” Dr. Phillips said.
As for Dr. Reppert, he is now planning his next step, that of understanding how the cryptochrome proteins sense the magnetic field and how they convey that information to the fruit fly’s and monarch’s brain.

Source The New York Times

Loophole found in genetic traffic laws

Altered molecule causes protein-making machinery to run stop signs.

Biology’s rules may be full of exceptions, but a new discovery has uncovered a violation in a rule so fundamental that geneticists call it the central dogma.
The molecular equivalent of writing one RNA letter in a different font can change the way a cell’s protein-building machinery interprets the genetic code, Yitao Yu and John Karijolich of the University of Rochester in New York report in the June 16 Nature. They found that occasional conversions of a genetic letter found in RNA into a slightly different form can cause a cell’s protein-building machinery to roll right through a stop sign.

That might seem like a run-of-the-mill molecular traffic violation, but it results in an entirely different protein than the one encoded by DNA — a clear violation of the central dogma.
The central dogma holds that DNA is the repository for all genetic instructions in a cell. The tenet declares that those instructions are carefully transcribed into multiple messenger RNA, or mRNA, copies, which are then read in three-letter chunks called codons by cellular machinery called ribosomes. Ribosomes then convert the mRNA instructions into proteins.

Yu and Karijolich studied pseudouridine, a slightly different version of the RNA component uridine. The enzymes that copy DNA to RNA and vice versa can’t tell the difference between the two components, but the subtle chemical tweak — akin to writing a letter in a hard-to-read, byzantine font — gives an entirely different meaning for the ribosome, the researchers suggest.
The result is “groundbreaking,” says Nina Papavasiliou, a molecular biologist at Rockefeller University in New York City. “It says that we don’t fully understand how ribosomes decode RNAs.”
That discovery could also mean that genes contain more information than scientists have realized, Papavasiliou says.

Pseudouridine is already known to be important for the function of many types of RNA in cells. Yu and Karijolich engineered a system to discover whether mRNAs containing the modified letter might also have a slightly different function than those with plain old uridine. The researchers created a flawed copper-detoxifying gene called CUP1 that contained an early signal to stop making protein. The team also created a system that would cause yeast cells to edit the mRNA, replacing the uridine in the stop codon with pseudouridine. If pseudouridine behaved just like uridine, then cells would prematurely halt production of the detoxifying protein and wouldn’t be able to grow in the presence of copper.
Yeast cells that replaced uridine in the stop sign with pseudouridine could grow on copper, the researchers found. Looking more closely, the team found that instead of reading the stop sign as stop, ribosomes interpreted the pseudouridine-containing codon as an instruction to insert the amino acids serine, threonine, phenylalanine or tyrosine into the protein.

That choice of amino acids by the ribosome has biologists reeling, because those aren’t even the amino acids usually chosen when the protein factories do occasionally run stop signs.
“When you know the literature, you would expect other [amino acids],” says Henri Grosjean, a biochemist and geneticist at the University of Paris-South.
Apparently ribosomes haven’t read those papers.

Whether pseudouridine plays a part in changing the genetic code in nature remains to be seen, but researchers are betting that it does. The implications for health and disease could be great, says Juan Alfonzo, a molecular biologist at the Ohio State University. Pseudouridines may be required to make some proteins correctly, but “misplacing a pseudouridine could make things a physiological mess,” he says, causing some proteins to have flaws, even fatal ones.
And Yu and Karijolich’s technique might be used to fix genetic errors, too. Introducing stop sign–busting pseudouridine into an RNA may one day help people with rare genetic diseases in which one of their genes contains an early stop codon, Alfonzo says.

Source Science News

Geneticists discover technique to tackle mutant DNA

Scientists at the University of Rochester believe they have found a way to alter the genes that can cause disease.

Scientists have hit on a genetic trick that opens up fresh avenues for the treatment of devastating diseases, such as cystic fibrosis, muscular dystrophy and certain forms of cancer.

The technique corrects glitches in genetic machinery that cause the body to make faulty versions of proteins that can lead to the onset of disease.
Although the work is at an early stage, the strategy represents a radical new approach to tackling mutations that give rise to an estimated one third of all genetic disorders.

"This is a really powerful concept that can be used to try to suppress the tendency of individuals to get certain debilitating, and sometimes fatal genetic diseases," said Robert Bambara at the University of Rochester Medical Centre, who was not involved in the study.
Proteins are the workhorses of the body and carry out all of the functions necessary for life, from metabolising food to building cells and directing immune attacks on unwelcome invaders. Taken together, the cells of the body make around 20,000 different proteins.

The instructions to make human proteins are carried by around 25,000 genes that are found in almost every cell. To make a protein, each "letter" of a gene must be copied into a single strand of genetic material called messenger RNA (mRNA). The cell then takes this mRNA and uses it as a blueprint to build the protein in a process called translation.
But the business of making proteins does not always proceed smoothly. Mutations in genes or mRNA can give rise to faulty proteins that in many cases trigger disease.
John Karijolich and Yi-Tao Yu at the University of Rochester Medical Centre focused on a type of mutation that causes strands of mRNA to contain premature "halt" signs called stop codons. These order cells to stop making proteins before the job is finished. As a result, affected cells churn out short and incomplete proteins.
Writing in the journal, Nature, the scientists describe a series of experiments in which they used short strands of RNA to correct faulty mRNA, by switching unwanted stop signs into "go" signs. To their surprise, treated cells began to produce healthy, full-length proteins again.

"This is a very exciting finding," Yu said. "No one ever imagined that you could alter a stop codon the way we have and allow translation to continue uninterrupted like it was never there in the first place."
"Our work is still really early with regard to clinical application," Yu told the Guardian. "However, we believe it will eventually offer a potential therapeutic option for premature stop codon-caused diseases, such as cystic fibrosis and muscular dystrophy."

Source The Guardian

Breeding with Neanderthals helped humans go global

WHEN the first modern humans left Africa they were ill-equipped to cope with unfamiliar diseases. But by interbreeding with the local hominins, it seems they picked up genes that protected them and helped them eventually spread across the planet.

The publication of the Neanderthal genome last year offered proof that Homo sapiens bred with Neanderthals after leaving Africa. There is also evidence that suggests they enjoyed intimate relations with other hominins including the Denisovans, a species identified last year from a Siberian fossil.

But what wasn't known is whether the interbreeding made any difference to their evolution. To find out Peter Parham of Stanford University in California took a closer look at the genes they picked up along the way.

He focused on human leukocyte antigens (HLAs), a family of about 200 genes that is essential to our immune system. It also contains some of the most variable human genes: hundreds of versions - or alleles - exist of each gene in the population, allowing our bodies to react to a huge number of disease-causing agents and adapt to new ones.

The humans that left Africa probably carried only a limited number of HLA alleles as they likely travelled in small groups. Worse, their HLAs would have been adapted to African diseases.

When Parham compared the HLA genes of people from different regions of the world with the Neanderthal and Denisovan HLAs, he found evidence that non-African humans picked up new alleles from the hominins they interbred with.

One allele, HLA-C*0702, is common in modern Europeans and Asians but never seen in Africans; Parham found it in the Neanderthal genome, suggesting it made its way into H. sapiens of non-African descent through interbreeding. HLA-A*11 had a similar story: it is mostly found in Asians and never in Africans, and Parham found it in the Denisovan genome, again suggesting its source was interbreeding outside of Africa.

Parham points out that because Neanderthals and Denisovans had lived outside Africa for over 200,000 years by the time they encountered H. sapiens, their HLAs would have been well suited to local diseases, helping to protect migrating H. sapiens too.

While only 6 per cent of the non-African modern human genome comes from other hominins, the share of HLAs acquired during interbreeding is much higher. Half of European HLA-A alleles come from other hominins, says Parham, and that figure rises to 72 per cent for people in China, and over 90 per cent for those in Papua New Guinea.

This suggests they were increasingly selected for as H. sapiens moved east. That could be because humans migrating north would have faced fewer diseases than those heading towards the tropics of south-east Asia, says Chris Stringer of the Natural History Museum in London.

Parham presented his work at a Royal Society discussion meeting on human evolution in London last week.

 Source New Scientist

Researchers identify protein that improves DNA repair under stress

Findings could lead to treatments to prevent premature aging and cancer

Cells in the human body are constantly being exposed to stress from environmental chemicals or errors in routine cellular processes. While stress can cause damage, it can also provide the stimulus for undoing the damage. New research by a team of scientists at the University of Rochester has unveiled an important new mechanism that allows cells to recognize when they are under stress and prime the DNA repair machinery to respond to the threat of damage. Their findings are published in the current issue of Science.

The scientists, led by biologists Vera Gorbunova and Andrei Seluanov, focused on the most dangerous type of DNA damage – double strand breaks. Unrepaired, this type of damage can lead to premature aging and cancer. They studied how oxidative stress affects efficiency of DNA repair. Oxidative stress occurs when the body is unable to neutralize the highly-reactive molecules, which are typically produced during routine cellular activities.

The research team found that human cells undergoing oxidative stress synthesized more of a protein called SIRT6. By increasing SIRT6 levels, cells were able to stimulate their ability to repair double strand breaks. When the cells were treated with a drug that inactivated SIRT6, DNA repair came to a halt, thus confirming the role of SIRT6 in DNA repair. Gorbunova notes that the SIRT6 protein is structurally related to another protein, SIR2, which has been shown to extend lifespan in multiple model organisms.

"SIRT6 also affects DNA repair when there is no oxidative stress," explains Gorbunova. "It's just that the effect is magnified when the cells are challenged with even small amounts of oxidative stress." SIRT6 allows the cells to be economical with their resources, priming the repair enzymes only when there is damage that needs to be repaired. Thus SIRT6 may be a master regulator that coordinates stress and DNA repair activities, according to Gorbunova.

SIRT6 does not act alone to repair DNA. Gorbunova and her group also showed that, in response to stress, SIRT6 acts on a protein called PARP1 to initiate DNA repair. PARP1 is an enzyme that is one of the "first responders" to DNA damage and is involved in several DNA repair machineries. By increasing the levels of SIRT6, the Rochester team found that cells were able to more rapidly direct DNA repair enzymes to sites of damage and hasten the repair of double strand breaks.

The next step for Gorbunova and Seluanov is to identify the chemical activators that increase the activity of SIRT6. Once that discovery is made, Gorbunova said it may be possible to apply the results to therapies that prevent the onset of certain aging-related diseases.

Source  EurekaAlert!

Building a dinosaur from a chicken Can scientists convince birds to evolve backward .. into dinosaurs?

 Archaeopteryx lithographica at the Museum für Naturkunde in Berlin, Germany. (This is the original fossil -- not a cast.)

One of the most controversial topics in science during the past many decades has been the debate over the origin of birds: did they evolve from dinosaurs or reptiles? This debate quieted down for awhile until the discovery of an important new fossil in the nineteenth century. This fossil, known today as the Berlin specimen of Archaeopteryx (pictured above), led to fresh insights, thus reigniting this debate. Today, it is fairly well-accepted by the scientific community that birds are a special lineage of theropod dinosaurs.


When you look closely at the above fossil, you can see similarities as well as clear morphological differences between Archaeopteryx and, say, a chicken. Archaeopteryx has fingers instead of wings, Archaeopteryx has a long bony tail instead of a short bony nubbin and, if you look closely, you can also see that Archaeopteryx has teeth -- all of which birds lack.

But ornithologists and birders are familiar with one peculiar South American bird, the hoatzin, Opisthocomus hoazin, whose chicks possess claws on two of their wing digits -- almost like Archaeopteryx! But hoatzins aren't unique: curious traits, traits that had been lost during evolution, sometimes pop up in domestic livestock and even in humans -- chickens with teeth, horses with extra toes and humans with tails, for example. These features, known as atavisms, result from errors in gene regulation: genes are either "turned on" (expressed) or "turned off" (suppressed) at the incorrect times during development. Atavistic traits are reminders of the evolutionary past.

Knowing this, renown paleontologist Jack Horner has spent much of his career trying to turn back the evolutionary clock by reconstructing a dinosaur. He's found dinosaur fossils with extraordinarily well-preserved blood vessels and soft tissues, but never intact DNA. So instead of using the Jurassic Park method to recreate dinosaurs, he's taking a different approach. Mr Horner is taking a living descendant of the dinosaur -- chickens -- and genetically engineering them to reactivate ancestral traits -- including teeth, tails, and even hands. He's making a "chickenosaurus". In this fascinating video, Mr Horner reviews recent dinosaur discoveries and talks about his plans for recreating a "chickenosaurus":


Jack Horner studied geology and zoology but did not complete his bachelor's degree due to his inability to pass the required foreign language courses (he is somewhat dyslexic and could not read adequately in German). However, he did complete his senior thesis on the fauna of the Bear Gulch Limestone in Montana, which is one of the most famous Mississippian fossil sites in the world. He currently is Curator of Paleontology at the Museum of the Rockies and also serves in a number of academic capacities. In recognition of his achievements and contributions to the field of paleontology, he was awarded an Honorary Doctorate of Science in 1986 by the University of Montana and in 2006 by the Pennsylvania State University. In 1986, he was also awarded the prestigious MacArthur Fellowship. Mr Horner further discusses his plans to reconstruct a "chickenosaurus" in his 2009 book, How to Build a Dinosaur: Extinction Doesn't Have to Be Forever [Amazon UK; Amazon US].


Source The Guardian

Life-history traits may affect DNA mutation rates in males more than in females

For the first time, scientists have used large-scale DNA sequencing data to investigate a long-standing evolutionary assumption: DNA mutation rates are influenced by a set of species-specific life-history traits.

These traits include metabolic rate and the interval of time between an individual's birth and the birth of its offspring, known as generation time. The team of researchers led by Kateryna Makova, a Penn State University associate professor of biology, and first author Melissa Wilson Sayres, a graduate student, used whole-genome sequence data to test life-history hypotheses for 32 mammalian species, including humans. For each species, they studied the mutation rate, estimated by the rate of substitutions in neutrally evolving DNA segments -- chunks of genetic material that are not subject to natural selection. They then correlated their estimations with several indicators of life history. The results of the research will be published in the journal Evolution on 13 June 2011.

One of the many implications of this research is that life-history traits of extinct species now could be discoverable. "Correlations between life-history traits and mutation rates for existing species make it possible to develop a hypothesis in reverse for an ancient species for which we have genomic data, but no living individuals to observe as test subjects," Makova explained. "So, if we have information about how extant species' life history affects mutation rates, it becomes possible to make inferences about the life history of a species that has been extinct for even tens of thousands of years, simply by looking at the genomic data."

To find correlations between life history and mutation rates, the scientists first focused on generation time. "The expected relationship between generation time and mutation rate is quite simple and intuitive," Makova said. "The more generations a species has per unit of time, the more chances there are for something to go wrong; that is, for mutations or changes in the DNA sequence to occur." Makova explained that the difference between mice and humans could be used to illustrate how vastly generation time can vary from species to species. On the one hand, mice in the wild usually have their first litter at just six months of age, and thus their generation time is very short. Humans, on the other hand, have offspring when they are at least in their mid-teens or even in their twenties, and thus have a longer generation time. "If we do the math we see that, for mice, every 100 years equates to about 200 generations, whereas for humans, we end up with only five generations every 100 years," Makova said. After comparing 32 mammalian species, her team found that the strongest, most significant life-history indicator of mutation rate was, in fact, the average time between a species member's birth and the birth of its first offspring, accounting for a healthy 40% of mutation-rate variation among species.

Makova's team also found that generation time affects male mutation bias -- a higher rate of DNA mutation in the male sperm versus the female egg. "Females of a species are born with their entire lifetime supply of oocytes, or egg cells. These cells have to divide only once to become fertilizable," Makova explained. "However, males of a species produce sperm throughout their reproductive life, and, compared with egg cells, sperm cells undergo many more DNA replications -- many more chances for mutations to occur." Previous researchers had demonstrated a higher DNA mutation rate in mammalian males than in mammalian females, a phenomenon called male mutation bias. However, until now, no one had shown that generation time was the main determinant of this phenomenon.

The second life-history trait that Makova's team examined was metabolic rate -- the amount of energy expended by an animal daily -- and how it correlates with genetic mutations. Wilson Sayres explained that some of the team's 32 test species, such as shrews and rodents, fell into the high-metabolism category, while others, such as dolphins and elephants, fell into the low-metabolism category. Previous researchers had hypothesized that the higher the metabolic rate, the greater the number of mutations. "According to this idea, sperm cells should be more affected than egg cells by a higher metabolic rate," Wilson Sayres said. "A sperm cell is very active and constantly moving, and, in addition, its cell membrane is not very dense. But an egg cell basically sits there and does nothing, while being protected by a thicker membrane, much like a coat of armor." Wilson Sayres explained that the combination of high energy and meager protection leaves sperm cells more susceptible to bombardment by free radicals -- atoms or molecules with unpaired electrons -- and that these free radicals can increase mutations. "The hypothesis is that a high metabolism greatly increases this already volatile situation, especially for sperm; so, in our study, we expected stronger male mutation bias in organisms with high metabolic rate," Wilson Sayres said.

Makova's team found that, unlike generation time, metabolic rate appeared to be only a moderate predictor of mutation rates and of male mutation bias. "While this finding was not as significant as the generation-time result, I suspect that further studies may provide stronger evidence that metabolic rate exerts an important influence on mutation rates and male mutation bias," Makova said. She explained that the challenge is to disentangle metabolic rate as a separate factor from generation time. "The two factors strongly correlate with one another, so it's hard to get a clear fix on how metabolism might be acting independently of generation-time intervals."

Third, Makova and her team explored another life-history trait that other researchers had hypothesized might affect mutation rates -- sperm competition. "Sperm competition is just that -- the struggle between the sperm of different males to fertilize egg cells," Wilson Sayres said. "In a species such as the chimpanzee, where females mate with many different males during a given cycle, intense sperm competition results in large testicle size, and thus, high sperm production. But in a harem species such as the gorilla, where each female is basically exclusive to one male, sperm competition is much less relevant, and the result is small testicle size and low sperm production." Makova explained that sperm competition should, in theory, correlate positively with sperm mutation and thus a higher male mutation bias. "The more sperm that are produced, the more cell divisions are needed and the greater the chances are of mistakes during DNA copying, or replication," Makova said.

However, in the case of sperm competition, the results were surprising. "We did not find as strong an association between male mutation bias and sperm competition as other researchers had hypothesized, although we speculate that future studies might yield different results if the data on sperm competition are collected in different ways," Wilson Sayres explained.

Source EurekaAlert!

We are all mutants

First direct whole-genome measure of human mutation predicts 60 new mutations in each of us.


Each one of us receives approximately 60 new mutations in our genome from our parents.
This striking value is reported in the first-ever direct measure of new mutations coming from mother and father in whole human genomes published today.

For the first time, researchers have been able to answer the questions: how many new mutations does a child have and did most of them come from mum or dad? The researchers measured directly the numbers of mutations in two families, using whole genome sequences from the 1000 Genomes Project. The results also reveal that human genomes, like all genomes, are changed by the forces of mutation: our DNA is altered by differences in its code from that of our parents. Mutations that occur in sperm or egg cells will be 'new' mutations not seen in our parents.

Although most of our variety comes from reshuffling of genes from our parents, new mutations are the ultimate source from which new variation is drawn. Finding new mutations is extremely technically challenging as, on average, only 1 in every 100 million letters of DNA is altered each generation.
Previous measures of the mutation rate in humans has either averaged across both sexes or measured over several generations. There has been no measure of the new mutations passed from a specific parent to a child among multiple individuals or families.

"We human geneticists have theorised that mutation rates might be different between the sexes or between people," explains Dr Matt Hurles, Senior Group Leader at the Wellcome Trust Sanger Institute, who co-led the study with scientists at Montreal and Boston, "We know now that, in some families, most mutations might arise from the mother, in others most will arise from the father. This is a surprise: many people expected that in all families most mutations would come from the father, due to the additional number of times that the genome needs to be copied to make a sperm, as opposed to an egg."

Professor Philip Awadalla,who also co-led the project and is at University of Montreal explained: "Today, we have been able to test previous theories through new developments in experimental technologies and our analytical algorithms. This has allowed us to find these new mutations, which are like very small needles in a very large haystack."
The unexpected findings came from a careful study of two families consisting of both parents and one child. The researchers looked for new mutations present in the DNA from the children that were absent from their parents' genomes. They looked at almost 6000 possible mutations in the genome sequences.
They sorted the mutations into those that occurred during the production of sperm or eggs of the parents and those that may have occurred during the life of the child: it is the mutation rate in sperm or eggs that is important in evolution. Remarkably, in one family 92 per cent of the mutations derived from the father, whereas in the other family only 36 per cent were from the father.

This fascinating result had not been anticipated, and it raises as many questions as it answers. In each case, the team looked at a single child and so cannot tell from this first study whether the variation in numbers of new mutations is the result of differences in mutation processes between parents, or differences between individual sperm and eggs within a parent.
Using the new techniques and algorithms, the team can look at more families to answer these new riddles, and address such issues as the impact of parental age and different environment exposures on rates of new mutations, which might concern any would-be parent.

Equally remarkably, the number of mutations passed on from a parent to a child varied between parents by as much as tenfold. A person with a high natural mutation rate might be at greater risk of misdiagnosis of a genetic disease because the samples used for diagnosis might contain mutations that are not present in other cells in their body: most of their cells would be unaffected.

Source  EurekaAlert!

New genetic technique converts skin cells into brain cells

A research breakthrough has proven that it is possible to reprogram mature cells from human skin directly into brain cells, without passing through the stem cell stage. The unexpectedly simple technique involves activating three genes in the skin cells; genes which are already known to be active in the formation of brain cells at the foetal stage.

The new technique avoids many of the ethical dilemmas that stem cell research has faced.
For the first time, a research group at Lund University in Sweden has succeeded in creating specific types of nerve cells from human skin. By reprogramming connective tissue cells, called fibroblasts, directly into nerve cells, a new field has been opened up with the potential to take research on cell transplants to the next level. The discovery represents a fundamental change in the view of the function and capacity of mature cells. By taking mature cells as their starting point instead of stem cells, the Lund researchers also avoid the ethical issues linked to research on embryonic stem cells.

Head of the research group Malin Parmar was surprised at how receptive the fibroblasts were to new instructions.
“We didn’t really believe this would work, to begin with it was mostly just an interesting experiment to try. However, we soon saw that the cells were surprisingly receptive to instructions.”
The study, which was published in the latest issue of the scientific journal PNAS, also shows that the skin cells can be directed to become certain types of nerve cells.

In experiments where a further two genes were activated, the researchers have been able to produce dopamine brain cells, the type of cell which dies in Parkinson’s disease. The research findings are therefore an important step towards the goal of producing nerve cells for transplant which originate from the patients themselves. The cells could also be used as disease models in research on various neurodegenerative diseases.

Unlike older reprogramming methods, where skin cells are turned into pluripotent stem cells, known as IPS cells, direct reprogramming means that the skin cells do not pass through the stem cell stage when they are converted into nerve cells. Skipping the stem cell stage probably eliminates the risk of tumours forming when the cells are transplanted. Stem cell research has long been hampered by the propensity of certain stem cells to continue to divide and form tumours after being transplanted.

Before the direct conversion technique can be used in clinical practice, more research is needed on how the new nerve cells survive and function in the brain. The vision for the future is that doctors will be able to produce the brain cells that a patient needs from a simple skin or hair sample. In addition, it is presumed that specifically designed cells originating from the patient would be accepted better by the body’s immune system than transplanted cells from donor tissue.

“This is the big idea in the long run. We hope to be able to do a biopsy on a patient, make dopamine cells, for example, and then transplant them as a treatment for Parkinson’s disease”, says Malin Parmar, who is now continuing the research to develop more types of brain cells using the new technique.

Source Lund University

Cryptic Mutations Could Be Evolution’s Hidden Fuel

The transformation of raw genetic material on a laboratory bench has provided a rare empirical demonstration of processes that may be universally crucial to evolution, but are only beginning to be understood.
The processes, called cryptic variation and preadaptation, involve mutations that don’t affect an organism when they first occur, and are initially exempt from pressures of natural selection. As they gather, however, at some later date, they could combine to form the basis for complex, unpredictable new traits.
In the new study, the ability of evolving, chemical-crunching molecules called ribozymes to adapt in new environments proved directly related to earlier accumulations of cryptic mutations. The details are esoteric, but their implications involve the very essence of adaptation and evolution.

“It’s one of the more modern topics in evolutionary theory,” said mathematical biologist Joshua Plotkin of the University of Pennsylvania, author of a commentary on the experiment, which was described June 2 in Nature. “The idea has been around for a while, but direct evidence hasn’t been found until recently.”

The experiment was led by evolutionary biologists Eric Hayden and Andreas Wagner of Switzerland’s University of Zurich, who use ribozymes — molecules made from RNA, a single-stranded form of genetic material – to study evolutionary principles in the simplest possible way.
The principles of cryptic variation and preadaptation were first proposed in the mid-20th century and conceptually refined in the mid-1970s. They were logical answers to the question of how complex traits, seemingly far too complex to be explained by one or a few mutations, could arise.

But even as such leading thinkers as Stephen Jay Gould embraced the concept, it proved difficult to study in detail. The tools didn’t exist to interpret genetic data with the necessary rigor. The concept itself was also difficult to grasp, injecting long periods of accumulation, purposeless mutations into an evolutionary narrative supposedly driven by constant selection.
In recent years, however, with the advent of better tools and a growing appreciation for evolution’s sheer complexity, researchers’ attention has turned again to cryptic variation and preadaptation. Computer models and scattered observations in bacteria and yeast hinted at their importance. But definitive proof, combining exhaustive genetic observation with real-world evolution, was elusive.

“Cryptic variation addresses questions of innovation,” said Hayden. “How do new things come about in biology? There’s been a long history of this concept, but no concrete experimental demonstration.”
In the new study, Hayden and Wagner evolved ribozymes in test tubes of chemicals, then moved them to a new chemical substrate, a shift analogous to requiring animals to suddenly subsist on a new food source.
The ribozymes that flourished were those that had accumulated specific sets of cryptic mutations in their former environment. Those variations, seemingly irrelevant before, became the basis of newly useful adapation. The researchers were able to measure every change in detail.
“It is a groundbreaking proof of principle,” said University of Arizona evolutionary biologist Joanna Masel, who wasn’t involved in the study. “This study is a clear demonstration that cryptic genetic variation can make evolution more effective.”

According to Plotkin, cryptic variation and preadaptation may be crucial to the evolution of drug resistance and immune system evasion in pathogens. Rather than looking for straightforward mutations, researchers could search for combinations, perhaps developing an “advance warning system” to flag seemingly innocuous changes.
Another application could be in genetic engineering. Whereas virus and bacteria designers tend to “accept any mutations that get them closer to their intended outcome,” said Plotkin, “it might be important to take lateral steps as well as uphill steps.”

Cryptic variation and preadaptation could also be important to the evolution of animals, from the origin of multicellularity to complex features like eyes and language. Plotkin would like to see studies revisiting the evolution of Charles Darwin’s famous finch beaks, but with an eye toward these newly described processes.
Masel said that better understanding cryptic variation and preadaptation could help programmers of evolving computer systems, and perhaps explain why some systems are better able than others to evolve. “Why are biological systems so evolvable?” she said. “This dynamic may or may not be the essence of evolvability. That’s certainly one of the hypotheses out there, and I am enthusiastic about it.”

These processes could also help interpret genomic studies that loosely link hundreds or thousands of genetic mutations to disease and development, frustrating geneticists searching for genetic patterns of heritability, said Masel and Hayden. And at a social level, they could be instructive to people interested in fostering innovation.
“My prediction is that it is good to foster lots of variation,” said Masel, who likened cryptic variation and preadaptation to Google’s famous requirement that employees spend 20 percent of their time on projects of personal whimsy. Rather than focusing narrowly on ideas that are obviously good, “Foster circumstances where lots of non-terrible ideas are floating around,” said Masel.

Source WIRED

Deadly bacteria may mimic human proteins to evolve antibiotic resistance

Analysis of Next-Generation genomewide datasets needed to target development of new drug treatments.

FLAGSTAFF, Ariz. — June 1, 2011 — Deadly bacteria may be evolving antibiotic resistance by mimicking human proteins, according to a new study by the Translational Genomics Research Institute (TGen).
This process of "molecular mimicry" may help explain why bacterial human pathogens, many of which were at one time easily treatable with antibiotics, have re-emerged in recent years as highly infectious public health threats, according to the study published May 26 in the journal Public Library of Science (PLoS) One.
"This mimicry allows the bacteria to evade its host's defense responses, side-stepping our immune system," said Dr. Mia Champion, an Assistant Professor in TGen's Pathogen Genomics Division, and the study's author.

Using genomic sequencing, the spelling out of billions of genetic instructions stored in DNA, the study identified several methyltransferase protein families that are very similar in otherwise very distantly related human bacterial pathogens. These proteins also were found in hosts such as humans, mouse and rat.
Researchers found methyltransferase in the pathogen Francisella tularensis subspecies tularensis, the most virulent form of Francisella. Just one cell can be lethal. Methyltransferase is a potential virulence factor in this pathogen, which causes Tularemia, an infection common in wild rodents, especially rabbits, that can be transmitted to humans though bites, touch, eating or drinking contaminated food or water, or even breathing in the bacteria. It is severely debilitating and even fatal, if not treated.
Similar methyltransferase proteins are found in other highly infectious bacteria, including the pathogen Mycobacterium tuberculosis that causes Tuberculosis, a disease that results in more than 1 million deaths annually. The study also identified distinct methyltransferase subtypes in human pathogens such as Coxiella, Legionella, and Pseudomonas.

In general, these bacterial pathogens are considered "highly clonal," meaning that the overall gene content of each species is very similar. However, the study said, "The evolution of pathogenic bacterial species from nonpathogenic ancestors is … marked by relatively small changes in the overall gene content."
Genomic comparisons were made with several strains of the bacteria, as well as with plants and animals, including humans. The methyltransferase protein also was found to have an ortholog, or similar counterpart, in human DNA. Although the overall sequence of the orthologs is highly similar, the study identifies a protein domain carrying distinct amino acid variations present in the different organisms.

"Altogether, evidence suggests a role of the Francisella tularensis protein in a mechanism of molecular mimicry. Upon infection, bacterial pathogens dump more than 200 proteins into human macrophage cells called 'effector proteins.' Because these proteins are so similar to the human proteins, it mimics them and enables them to interfere with the body's immunity response, thereby protecting the pathogen,'' Dr. Champion said.
"These findings not only provide insights into the evolution of virulence in Francisella, but have broader implications regarding the molecular mechanisms that mediate host-pathogen relationships," she added.
Identifying small differences between the pathogen and human proteins through Next Generation genome-wide datasets could help develop molecular targets in the development of new drug treatments, she said.

Source EurekaAlert!

Arrowing in on Alzheimer's disease

Recently the number of genes known to be associated with Alzheimer's disease has increased from four to eight, including the MS4A gene cluster on chromosome 11.

New research published in BioMed Central's open access journal Genome Medicine has expanded on this using a genome-wide association study (GWAS) to find a novel location within the MS4A gene cluster which is associated with Alzheimer's disease.

Alzheimer's disease is the most common cause of dementia in the developed world. It irrevocably destroys cells in the brain that are responsible for intellectual ability and memory. Despite continued investigation, the causes of Alzheimer's disease are not yet fully understood but they are thought to be a mixture of genetic and environmental factors. Several studies have used GWAS to search the entire human genome for genes which are mutated in Alzheimer's sufferers in the hope of finding a way to treat or slow down the disease.

A team of researchers across Spain and USA sponsored by non-profit Fundación Alzheimur (Comunidad Autónoma de la Región de Murcia) and Fundació ACE Institut Català de Neurociències Aplicades performed their own GWAS study using patients with Alzheimer's disease, and non-affected controls, from Spain and then combined their results with four public GWAS data sets. Dr Agustín Ruiz said, "Combining these data sets allowed us to look more accurately at small genetic defects. Using this technique we were able to confirm the presence of mutations (SNP) known to be associated with Alzheimer's disease, including those within the MS4A cluster, and we also found a novel site."

Dr Ruiz continued, "Several of the 16 genes within the MS4A cluster are implicated in the activities of the immune system and are probably involved in allergies and autoimmune disease. MS4A2 in particular has been linked to aspirin-intolerant asthma. Our research provides new evidence for a role of the immune system in the progression of Alzheimer's disease."

Source EurekaAlert!

Researchers solve mammoth evolutionary puzzle: The woollies weren't picky, happy to interbreed

A DNA-based study sheds new light on the complex evolutionary history of the woolly mammoth, suggesting it mated with a completely different and much larger species.

The research, which appears in the BioMed Central's open access journal Genome Biology, found the woolly mammoth, which lived in the cold climate of the Arctic tundra, interbred with the Columbian mammoth, which preferred the more temperate regions of North America and was some 25 per cent larger.
"There is a real fascination with the history of mammoths, and this analysis helps to contextualize its evolution, migration and ecology" says Hendrik Poinar, associate professor and Canada Research Chair in the departments of Anthropology and Biology at McMaster University.

Poinar and his team at the McMaster Ancient DNA Centre, along with colleagues from the United States and France, meticulously sequenced the complete mitochondrial genome of two Columbian mammoths, one found in the Huntington Reservoir in Utah, the other found near Rawlins, Wyoming. They compared these to the first complete mitochrondrial genome of an endemic North American woolly mammoth.

"We are talking about two very physically different 'species' here. When glacial times got nasty, it was likely that woollies moved to more pleasant conditions of the south, where they came into contact with the Columbians at some point in their evolutionary history," he says. "You have roughly 1-million years of separation between the two, with the Columbian mammoth likely derived from an early migration into North American approximately 1.5-million years ago, and their woolly counterparts emigrating to North America some 400,000 years ago."

"We think we may be looking at a genetic hybrid," says Jacob Enk, a graduate student in the McMaster Ancient DNA Centre. "Living African elephant species hybridize where their ranges overlap, with the bigger species out-competing the smaller for mates. This results in mitochondrial genomes from the smaller species showing up in populations of the larger. Since woollies and Columbians overlapped in time and space, it's not unlikely that they engaged in similar behaviour and left a similar signal."
The samples used for the analyses date back approximately 12,000 years. All mammoths became extinct approximately 10,000 years ago except for small isolated populations on islands off the coast of Siberia and Alaska.

Source  EurekaAlert!

What is a laboratory mouse? Jackson, UNC researchers reveal the details

Bar Harbor, Maine -- Mice and humans share about 95 percent of their genes, and mice are recognized around the world as the leading experimental model for studying human biology and disease. But, says Jackson Laboratory Professor Gary Churchill, Ph.D., researchers can learn even more "now that we really know what a laboratory mouse is, genetically speaking."

Churchill and Fernando Pardo-Manuel de Villena, Ph.D., of the University of North Carolina, Chapel Hill, leading an international research team, created a genome-wide, high-resolution map of most of the inbred mouse strains used today. Their conclusion, published in Nature Genetics: Most of the mice in use today represent only limited genetic diversity, which could be significantly expanded with the addition of more wild mouse populations.

The current array of laboratory mouse strains is the result of more than 100 years of selective breeding. In the early 20th century, America's first mammalian geneticists, including Jackson Laboratory founder Clarence Cook Little, sought to understand the genetic processes that lead to cancer and other diseases. Mice were the natural experimental choice as they breed quickly and prolifically and are small and easy to keep.
Lacking the tools of molecular genetics, those early scientists started by tracking the inheritance of physical traits such as coat color. A valuable source of diverse-looking mouse populations were breeders of "fancy mice," a popular hobby in Victorian and Edwardian England and America as well as for centuries in Asia.
In their paper, Churchill and Pardo-Manuel de Villena report that "classical laboratory strains are derived from a few fancy mice with limited haplotype diversity." In contrast, strains that were derived from wild-caught mice "represent a deep reservoir of genetic diversity," they write.

The team created an online tool, the Mouse Phylogeny Viewer, for the research community to access complete genomic data on 162 mouse strains. "The viewer provides scientists with a visual tool where they can actually go and look at the genome of the mouse strains they are using or considering, compare the differences and similarities between strains and select the ones most likely to provide the basis for experimental results that can be more effectively extrapolated to the diverse human population," said Pardo-Manuel de Villena.

"As scientists use this resource to find ways to prevent and treat the genetic changes that cause cancer, heart disease, and a host of other ailments, the diversity of our lab experiments should be much easier to translate to humans," he noted.
Churchill and Pardo-Manuel de Villena have been working for almost a decade with collaborators around the world to expand the genetic diversity of the laboratory mouse. In 2004 they launched the Collaborative Cross, a project to interbreed eight different strains--five of the classic inbred strains and three wild-derived strains. In 2009 Churchill's lab started the Diversity Outbred mouse population with breeding stock selected from the Collaborative Cross project.

The research team estimates that the standard laboratory mouse strains carry about 12 million single nucleotide polymorphisms (SNPs), single-letter variations in the A, C, G or T bases of DNA. The Collaborative Cross mice deliver a whopping 45 million SNPs, as much as four times the genetic variation in the human population. "All these variants give us a lot more handles into understanding the genome," Churchill says.

"This work creates a remarkable foundation for understanding the genetics of the laboratory mouse, a critical model for studying human health," said James Anderson, Ph.D., who oversees bioinformatics grants at the National Institutes of Health. "Knowledge of the ancestry of the many strains of this invaluable model vertebrate will not only inform future experimentation but will allow a retrospective analysis of the huge amounts of data already collected."

Source EurekaAlert!

Clone army steals genes from other species

Species: Corbicula fluminea

Habitat: originally from south-east Asia, this un-frisky mollusc has spread round the world

Anyone who thinks that invading clone armies are the preserve of science fiction should think again. One is marching across Europe and north America at this very moment.

 This seemingly celibate clam has sex on occasion

The clones in question are Asian clams, or Corbicula fluminea, a species of freshwater mollusc that originated in China and Taiwan. They aren't popular in their new homes, clogging up water intake pipes and outcompeting native clams. But they have some remarkable sexual talents.

Each clam is a hermaphrodite with both male and female sexual organs – by fertilising its own eggs, it can clone itself. It is also a parasite that commandeers the eggs of other clams for its own purposes and, every so often, it steals their genes too.

The trouble with celibacy

By not having sex, C. fluminea avoids the risks of finding a mate – just ask female cowpea weevils or male spiders why that's a good idea. But if all individuals of a species go without sex, over time harmful mutations build up and the species can go extinct.

"There are almost certainly systems where strict asexuality arises, and the lineages go extinct over evolutionary time – thousands or tens of thousands of years," says David Hillis of the University of Texas at Austin. For an asexual species to survive in the long run, it must refresh its genes every so often.

The poster children for asexuality are bdelloid rotifers, tiny animals that have gone without sex for 80 million years. But they cheat: they steal swathes of genes from bacteria, fungi and plants.

Other asexual animals have similar tricks, but until now it was thought C. fluminea had no way to get new genes. Now Hillis has figured out how they do it.

No girl genes, please

When a clam wants to reproduce, it uses its own sperm to fertilise its own egg. At this point the embryo isn't on course to be a clone, because the genes from the sperm and egg could get jumbled up – in effect, the clam would have sex with itself. But the embryo ejects all the genes that came from the egg, so only the genes from the sperm make it into the developing clone.

Sometimes the clams pull the same trick with eggs from other clams of the same species, fertilising them and then dumping their genes. In effect, they parasitise each other's eggs.

That isn't so bad: at least everyone parasitises everyone else. But it's horribly bad luck for clams of a sexual clam species if an Asian clam parasitises their eggs as they have no comeback.

It's this commandeering of other species' eggs that Hillis thinks is at the root of the clams' survival. He and his colleagues compared the DNA from 10 Corbicula species, some of which were sexual and some asexual. They found that some genes in the clams' nuclear DNA were the same in both sexual and asexual species. That wouldn't happen if the asexual species were strict cloners.

An injection of genes

Hillis thinks this can be explained if the asexual clams sometimes fertilise eggs from another species and retain some or all of their genes, rather than ejecting them. That would give their offspring an injection of fresh genes. He says this sort of genetic theft may be much more common in the animal kingdom than anyone realises.

He points to cases where two asexual species of Corbicula were introduced to north America, and over time one species captured mitochondrial genes from the other. Capturing nuclear genes is much rarer, but the clams' DNA suggests it does happen.

The lesson is clear: everyone is at it, and it's for their own good. Even C. fluminea and their seemingly celibate cousins have sex on the odd occasion.

Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1106742108

Source New Scientist

Nottingham scientists reveal genetic 'wiring' of seeds

The genetic 'wiring' that helps a seed to decide on the perfect time to germinate has been revealed by scientists for the first time.

Plant biologists at The University of Nottingham have also discovered that the same mechanism that controls germination is responsible for another important decision in the life cycle of plants — when to start flowering.
Their discovery throws light on the genetic mechanisms that plants use to detect and respond to vital environmental cues and could be a significant step towards the development of new crop species that are resistant to climate change and would help secure future food supplies.

Seeds in the soil sense a whole range of environmental signals including temperature, light, moisture and nutrients, when deciding whether to germinate or to remain dormant.
To ensure that the decision for a seed to germinate is made at the perfect moment to ensure survival, evolution has genetically 'wired' seeds in a very complex way to avoid making potentially deadly mistakes.

The breakthrough has been made by scientists at Nottingham's Division of Crop and Plant Sciences who collaborate within one of the University's Research Priority Groups, Global Food Security. The team compiled publicly available gene expression data and used a systematic statistical analysis to untangle the complex web of genetic interactions in a model plant called Arabidopsis thaliana or thale cress. The plant is commonly used for studying plant biology as changes in the plant are easily observed and it was the first plant to have its entire genome sequenced.

The resulting gene network — or SeedNet as it was dubbed — highlighted what little scientists already know about the regulation of seed germination while being able to predict novel regulators of this process with remarkable accuracy.

The work was led by Dr George Bassel who joined The University of Nottingham on an NSERC PDF fellowship from the Canadian government to work with Professor Mike Holdsworth on research into seed germination. He has since been awarded a prestigious Marie Curie International Incoming Fellowship.
Dr Bassel said: "To our surprise, the seed network demonstrated that genetic factors controlling seed germination were the same as those controlling the other irreversible decision in the life cycle of plants: the decision to start flowering. The induction of flowering, like germination, is highly responsive to cues from the environment."

Another key finding from SeedNet was that the same genes that leaves and roots use to respond to stress are used by seeds to stop their germination. Given that seeds were evolved long after plants developed their ability to withstand environmental stress, this indicated that plants have adapted existed genes to fulfil a different role. The work could lead to identifying important factors controlling stress response in seeds and the plant itself, contributing towards the development of new crops producing increased yields under extreme environmental conditions such as drought or floods.

 Source EurekaAlert!

Calculations may have overestimated extinction rates

THE destruction of nature is driving species to extinction - but perhaps not as rapidly as has been thought. While the most widely publicised estimates predict the loss of natural habitat will condemn 18 to 35 per cent of all species to extinction by 2050, these figures could be about twice as high as the actual number - all because of a mathematical error that has gone unnoticed for decades.

We still face an extinction crisis, warn Stephen Hubbell of the University of California, Los Angeles, and Fangliang He of Sun Yat-sen University in Guangzhou, China. But the pair's work will allow biologists to more precisely define how habitat destruction leads to extinction.

It is impossible to accurately measure extinction rates. Dozens of new species are identified each year, and counting those that disappear is hard because many are small and live in poorly studied, mainly tropical environments.

Instead, extinction rates are often predicted from a mathematical model based on habitat loss, which is more easily measured. The larger the area you survey, the more species you encounter. Ecologists calculate a curve called the species area relationship (SAR) for an ecosystem by measuring the area they must survey to encounter the first individual of each successive species. To establish the number of extinctions caused by habitat destruction, they run the SAR calculation in reverse.

"We had a feeling there were problems with this, but we could not say why mathematically," Hubbell says. So Hubbell and He checked the method using data from forest plots located all over the world. The pair could calculate the SAR for each plot, and also see what happened to species unique to these plots if they "destroyed" a certain area of each plot in their mathematical model. As the area of destruction widened, these species began to die out. But after each simulated loss of habitat, "more species always remained than were expected from the SAR", says Hubbell.

The pair's analysis explains why. Using the reverse SAR method, biologists have assumed that a species is lost with the destruction of an area of habitat equivalent to the area needed to first encounter it. But in reality, the species is lost only with destruction of the habitat area that includes every individual of the species, which is always larger. Consequently, the SAR method loses species too fast.

The duo developed a model relating extinction rate instead to the entire area occupied by a species. Using the forest data, and extensive data sets on birds, they found that the SAR gave extinction rates that were between 83 and 165 per cent higher than those their method produced (Nature, DOI: 10.1038/nature09985).

Similarly detailed information does not exist for most of the world's species, making it difficult to apply Hubbell and He's model more generally. "As a rule of thumb, we might correct traditional extinction rates by dividing them by factor of 2 to 2.5," says He.

Jean-Christophe Vié, deputy head of species survival at the International Union for the Conservation of Nature, agrees better baseline data on species is badly needed. He says IUCN doesn't use the SAR method. But, he points out, "a twofold miscalculation doesn't make much difference to an extinction rate now 100 to 1000 times the natural background".

Hubbell and He agree: "Mass extinction might already be upon us."

Conservation under scrutiny

Improvements to the science of extinction come at a good time: conservation scientists are about to come under the kind of scrutiny now experienced by climate scientists. In October, countries in the Convention on Biological Diversity plan to launch an Intergovernmental Platform on Biodiversity and Ecosystem Services, a scientific advisory panel similar to the Intergovernmental Panel on Climate Change.

There have been calls for this for a long time. Now the challenge will be to reach a consensus – a lack of which may have allowed some researchers to make inflated claims, says Carsten Rahbek of the University of Copenhagen, Denmark. "Scientists working for conservation organisations have used the SAR method (see main story) to get high estimates [of extinction rates]."

However, the increasing scarcity of funding to gather basic data on what species are where will make consensus-building difficult. At the same time, research will face greater scrutiny as countries work to meet biodiversity treaty obligations. For example, the European Union's biodiversity strategy, published this month, aims to use some of the EU's massive farm budget to fund ecosystem services, such as boosting bee populations.

Source New Scientist

Researchers identify DNA region linked to depression

Researchers at Washington University School of Medicine in St. Louis and King's College London have independently identified DNA on chromosome 3 that appears to be related to depression.

Major depression affects approximately 20 percent of people at some point during their lives, and family studies have long suggested that depression risk is influenced by genetics. The new studies identify a DNA region containing up to 90 genes. Both are published May 16 in the American Journal of Psychiatry.

"What's remarkable is that both groups found exactly the same region in two separate studies," says senior investigator Pamela A. F. Madden, PhD, professor of psychiatry at Washington University. "We were working independently and not collaborating on any level, but as we looked for ways to replicate our findings, the group in London contacted us to say, 'We have the same linkage peak, and it's significant.'"

Madden and the other researchers believe it is likely that many genes are involved in depression. While the new findings won't benefit patients immediately, the discovery is an important step toward understanding what may be happening at the genetic and molecular levels, she says.

he group at King's College London followed more than 800 families in the United Kingdom affected by recurrent depression. The Washington University group gathered data from 91 families in Australia and another 25 families in Finland. At least two siblings in each family had a history of depression, but the Australian and Finnish participants were studied originally because they were heavy smokers.


"Major depression is more common in smokers, with lifetime reports as high as 60 percent in smokers seeking treatment," says lead author Michele L. Pergadia, PhD, research assistant professor of psychiatry at Washington University. "Smokers with depression tend to experience more nicotine withdrawal and may be more likely to relapse when trying to quit. Previous studies suggest that smoking and depression run together in families. In our study, we detected a region of the genome that travels with depression in families of smokers."

Meanwhile, the group in England was concerned primarily with recurrent depression. Although some of the families in the King's College London survey may have included heavy smokers, the researchers were primarily interested in people who were depressed.

"These findings are truly exciting," says Gerome Breen, PhD, lead author of the King's College London study. "For the first time, we have found a genetic region associated with depression, and what makes the findings striking is the similarity of the results between our studies."

From two different data sets, gathered for different purposes and studied in different ways, the research teams found what is known as a linkage peak on chromosome 3. That means that the depressed siblings in the families in both studies carried many of the same genetic variations in that particular DNA region.
Unlike many genetic findings, this particular DNA region has genome-wide significance. Often when researchers correct statistically for looking across the entire genome, what appeared originally to be significant becomes much less so. That was not the case with these studies.

Although neither team has isolated a gene, or genes, that may contribute to depression risk, the linkage peak is located on a part of the chromosome known to house the metabotropic glutamate receptor 7 gene (GRM7). Some other investigators have found suggestive associations between parts of GRM7 and major depression.
"Our linkage findings highlight a broad area," Pergadia says. "I think we're just beginning to make our way through the maze of influences on depression. The U.K. samples came from families known to be affected by depression. Our samples came from heavy smokers, so one thing we might do as we move forward is try to better characterize these families, to learn more about their smoking and depression histories, in addition to all of their genetic information in this area."

Pergadia says it may be worthwhile to start by combining the data sets from the two studies to see whether this region of chromosome 3 continues to exert a significant effect.
Although there is still work to do, the new studies are a very important step on the road to understanding how genes influence depression, according to Peter McGuffin, MB, PhD, director of the Medical Research Council Social, Genetic and Developmental Psychiatry Centre at King's College London.

"The findings are groundbreaking," says McGuffin, senior author of that study. "However, they still only account for a small proportion of the genetic risk for depression. More and larger studies will be required to find the other parts of the genome involved."

Source  EurekaAlert!