Epigenetics: A timeline

Researchers are clarifying epigenetic intricacies such as missing heritability, disease markers, methylated proteins, and imprinted genes. Learn about the history of epigenetics in this timeline spanning 130 years.

Scientists Create the First Synthetic Bacterial Genome

A team of 17 researchers at the J. Craig Venter Institute (JCVI) has created the largest man-made DNA structure by synthesizing and assembling the 582,970 base pair genome of a bacterium, Mycoplasma genitalium JCVI-1.0. This work, published online today in the journal Science by Dan Gibson, Ph.D., et al, is the second of three key steps toward the team’s goal of creating a fully synthetic organism. In the next step, which is ongoing at the JCVI, the team will attempt to create a living bacterial cell based entirely on the synthetically made genome.
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New clinical trial results show how personalized medicine will alter treatment of genetic disorders

One of the nation’s pre-eminent genetic researchers, Eric Hoffman, PhD, of Children’s Research Institute at Children’s National Medical Center, predicts that in relatively short order, medicine’s next innovation–individualized molecular therapies–will have the unprecedented ability to treat muscular dystrophies, and other disorders.

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Human genetic variation — Science’s ‘Breakthrough of the Year’

In 2007, researchers were dazzled by the degree to which genomes differ from one human to another and began to understand the role of these variations in disease and personal traits. Science and its publisher, AAAS, the nonprofit science society, recognize “Human Genetic Variation” as the Breakthrough of the Year, and identify nine other of the year’s most significant scientific accomplishments in the 21 December issue.

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Gene regulation, not just genes, is what sets humans apart from primates

The striking differences between humans and chimps aren’t so much in the genes we have, which are 99 percent the same, but in the way those genes are used, according to new research from a Duke University team.

It’s rather like the same set of notes being played in very different ways.

In two major traits that set humans apart from chimps and other primates – those involving brains and diet – gene regulation, the complex cross-talk that governs when genes are turned on and off, appears to be significantly different.

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Biologists discover a reason why chromosomes break, often leading to cancer

In the past ten years, researchers in genome stability have observed that many kinds of cancer are associated with areas where human chromosomes break. They have hypothesized – but never proven – that slow or altered replication led to the chromosomes breaking.

In a Tufts University study published in the Aug. 3 journal “Molecular Cell,” two molecular biologists have used yeast artificial chromosomes to prove the hypothesis. The Tufts researchers have found a highly flexible DNA sequence that increases fragility and stalls replication, which then causes the chromosome to break.

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Risk genes for multiple sclerosis uncovered

A large-scale genomic study has uncovered new genetic variations associated with multiple sclerosis (MS), findings that suggest a possible link between MS and other autoimmune diseases. The study, led by an international consortium of clinical scientists and genomics experts, is the first comprehensive study investigating the genetic basis of MS. Findings appear in the July 29 online edition of the New England Journal of Medicine.

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Mutating the entire genome

Genes account for only 2.5 percent of DNA in the human genetic blueprint, yet diseases can result not only from mutant genes, but from mutations of other DNA that controls genes. University of Utah researchers report in the journal Nature Genetics that they have developed a faster, less expensive technique for mutating those large, non-gene stretches of DNA.

 

 

 

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Ancient retrovirus sheds light on HIV pandemic

Human resistance to a retrovirus that infected chimpanzees and other nonhuman primates 4 million years ago ironically may be at least partially responsible for the susceptibility of humans to HIV infection today.

“This ancient virus is a battle that humans have already won. Humans are not susceptible to it and have probably been resistant throughout millennia,” said senior author Michael Emerman, Ph.D., a member of the Human Biology and Basic Sciences divisions at the Hutchinson Center. “However, we found that during primate evolution, this innate immunity to one virus may have made us more vulnerable to HIV.”

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Serious diseases genes revealed

A major advance in understanding the genetics behind several of the world’s most common diseases has been reported.The landmark Wellcome Trust study analysed DNA from the blood of 17,000 people to find genetic differences. They found new genetic variants for depression, Crohn’s disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and 2 diabetes.

The remarkable findings, published in Nature, have been hailed as a new chapter in medical science.

Read rest of the article at BBC Newssite

Nobel laureate James Watson receives his personal genome sequence

The $1 million, two-month project is a collaboration of 454 Life Sciences and the BCM Human Genome Sequencing Center (HGSC), said Dr. Richard Gibbs, director of the HGSC and a scientific advisor to the Connecticut-based company. The announcement, aside from its meaning to Watson, is significant because it demonstrates that it will be possible in the future to sequence anyone’s genome – a goal toward which many sequencing firms are working. The time and cost will decrease as the technology improves.

Dr. Watson will receive a DVD with his genomic sequence. He will decide which of his data will be published.
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Mechanism of microRNAs deciphered

Over 30% of our genes are under the control of small molecules called microRNAs. They prevent specific genes from being turned into protein and regulate many crucial processes like cell division and development, but how they do so has remained unclear. Now researchers from the European Molecular Biology Laboratory (EMBL) have developed a new method that uncovered the mode of action of microRNAs in a test tube. The study, which is published in the current online issue of Nature, reveals that microRNAs block the initiation of translation, the earliest step in the process that turns genetic information stored on messenger RNAs into proteins.
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New Genetic Risk Factors For Type 2 Diabetes Identified

In the most comprehensive look at genetic risk factors for type 2 diabetes to date, a U.S.-Finnish team, working in close collaboration with two other groups, has identified at least four new genetic variants associated with increased risk of diabetes and confirmed existence of another six. The findings of the three groups, published in the journal Science, boost to at least 10 the number of genetic variants confidently associated with increased susceptibility to type 2 diabetes — a disease that affects more than 200 million people worldwide.
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Major genetic study identifies clearest link yet to obesity risk

Scientists have identified the most clear genetic link yet to obesity in the general population as part of a major study of diseases funded by the Wellcome Trust, the UK’s largest medical research charity. People with two copies of a particular gene variant have a 70% higher risk of being obese than those with no copies.
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Gene profiling predicts resistance to breast cancer drug Herceptin

Using gene chips to profile tumors before treatment, researchers at Harvard and Yale Universities found markers that identified breast cancer subtypes resistant to Herceptin, the primary treatment for HER2-positive breast cancer. They say this advance could help further refine therapy for the 25 to 30 percent of breast cancer patients with this class of tumor.

In the February 15 issue of Clinical Cancer Research, the researchers found that HER2-positive tumors that did not respond to Herceptin expressed certain basal markers, growth factors and growth factor receptors. One of these, insulin-growth factor receptor 1(IGF-1R), was associated with a Herceptin response rate that was half that of tumors that did not express IGF-1R.
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Mapping the Cancer Genome

Pinpointing the genes involved in cancer will help chart a new course across the complex landscape of human malignancies.

“If we wish to learn more about cancer, we must now concentrate on the cellular genome.” Nobel laureate Renato Dulbecco penned those words more than 20 years ago in one of the earliest public calls for what would become the Human Genome Project. “We are at a turning point,” Dulbecco, a pioneering cancer researcher, declared in 1986 in the journal Science. Discoveries in preceding years had made clear that much of the deranged behavior of cancer cells stemmed from damage to their genes and alterations in their functioning. “We have two options,” he wrote. “Either try to discover the genes important in malignancy by a piecemeal approach, or & sequence the whole genome.”
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Scientists discover new gene that prevents multiple types of cancer

A decades-old cancer mystery has been solved by researchers at Cold Spring Harbor Laboratory (CSHL). “We not only found a critical tumor suppressor gene, but have revealed a master switch for a tumor suppressive network that means more targeted and effective cancer therapy in the future,” said CSHL Associate Professor Alea Mills, Ph.D. The study was published in the February issue of Cell.

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Faster, low cost sequencing technologies needed to drive era of personalized medicine

DNA testing is transforming health care and medicine, but current technologies only give a snapshot of an individual’s genetic makeup. Any patient wanting a complete picture of their inherited DNA, or genome, would drop their jaw at the sight of the bill — to the current tune of $10 million or more charged for every human or mammalian-sized genome sequenced.

The NHGRI, part of the National Institutes of Health (NIH), has set an ambitious target of $1,000 or less – a cost 10,000 times lower than current technology – to make genome sequencing a routine diagnostic tool in medical care. The reduced cost may allow doctors to tailor medical treatments to an individual’s genetic profile for diagnosing, treating, and ultimately preventing many common diseases such as cancer, heart disease, diabetes and obesity.
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Scientists discover new class of RNA

The last few years have been very good to ribonucleic acid (RNA). Decades after DNA took biology by storm, RNA was considered little more than a link in a chain–no doubt a necessary link, but one that, by itself, had little to offer. But with the discoveries of RNA interference and microRNAs, this meager molecule has been catapulted to stardom as a major player in genomic activity.

Now, a team of scientists led by David Bartel, a professor in MIT’s Department of Biology, has discovered an entirely new class of RNA molecules.

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Scientists map key landmarks in human genome

Dana-Farber Cancer Institute researchers have developed a powerful method for charting the positions of key gene-regulating molecules called nucleosomes throughout the human genome. The mapping tool could help uncover important clues for understanding and diagnosing cancer and other diseases, the scientists say. Moreover, it may shed light on the role of nucleosomes in the process of “reprogramming” an adult cell to its original embryonic state, which is a critical operation in cloning.
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Scientists find new genetic clue to cause of Alzheimer’s disease

Variations in a gene known as SORL1 may be a factor in the development of late onset Alzheimer’s disease, an international team of researchers has discovered. The genetic clue, which could lead to a better understanding of one cause of Alzheimer’s, is reported in Nature Genetics online, Jan. 14, 2007, and was supported in part by the National Institutes of Health (NIH).

The researchers suggest that faulty versions of the SORL1 gene contribute to formation of amyloid plaques, a hallmark sign of Alzheimer’s in the brains of people with the disease. They identified 29 variants that mark relatively short segments of DNA where disease-causing changes could lie. The study did not, however, identify specific genetic changes that result in Alzheimer’s.
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Scientists Crack the Genome of the Parasite Causing Trichomoniasis

Scientists have finally deciphered the genome of the parasite causing trichomoniasis, a feat that is already providing new approaches to improve the diagnosis and treatment of this sexually transmitted disease. According to the World Health Organization trichomoniasis affects an estimated 170 million people a year and is an under-diagnosed global health problem.

Led by Jane Carlton, Ph.D., an Associate Professor in the Department of Medical Parasitology at New York University School of Medicine, the team of scientists took four years to crack the surprisingly large genome of the single-celled parasite Trichomonas vaginalis. They published the draft sequence of the parasite’s genome in the Jan. 12, 2007, issue of the journal Science.

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Regulating the nuclear architecture of the cell

An organelle called the nucleolus resides deep within the cell nucleus and performs one of the cell’s most critical functions: it manufactures ribosomes, the molecular machines that convert the genetic information carried by messenger RNA into proteins that do the work of life.

Gary Karpen and Jamy Peng, researchers in the Life Sciences Division of the Department of Energy’s Lawrence Berkeley National Laboratory, have now discovered two pathways that regulate the organization of the nucleolus and other features of nuclear architecture, maintaining genome stability in the fruit fly Drosophila melanogaster.
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DNA Repair Teams’ Motto: ‘To Protect and Serve’

When you dial 911 you expect rescuers to pull up at your front door, unload and get busy—not park the truck down the street and eat donuts. It’s the same for a cell—just before it divides, it recruits protein complexes that repair breakage that may have occurred along the linear DNA chains making up your 46 chromosomes. Without repair, damage caused by smoking, chemical mutagens, or radiation might be passed on to the next generation.

However, in 2005, investigators at the Salk Institute for Biological Studies observed that before cell division some of these cellular paramedics inexplicably idle at undamaged chromosome ends, known as telomeres. Apparently the telomeres’ disheveled appearance —resembling that of broken DNA strands—raises a red flag.

Now, in a study published in the Nov. 17 issue of Cell, that same team led by Jan Karlseder, Ph.D, Hearst Endowment Assistant Professor in the Molecular and Cell Biology Laboratory, reveals why those repair crews are parked at the ends of chromosomes and in doing so answer fundamental questions about how chromosomal stability is maintained.
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How to Resurrect an Extinct Retrovirus

French researchers have resurrected a retrovirus that became trapped in the human genome about five million years ago. Pieced together from existing sequences in human DNA, the reconstructed virus was able to infect mammalian cells weakly, suggesting that it works similarly to the extinct organism.

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Researchers find smallest cellular genome

The smallest collection of genes ever found for a cellular organism comes from tiny symbiotic bacteria that live inside special cells inside a small insect.

The bacteria Carsonella ruddii has the fewest genes of any cell. The bacteria’s newly sequenced genome, the complete set of DNA for the organism, is only one-third the size of the previously reported “smallest” cellular genome.
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Genetic repair mechanism clears the way for sealing DNA breaks

Scientists investigating an important DNA-repair enzyme now have a better picture of the final steps of a process that glues together, or ligates, the ends of DNA strands to restore the double helix.

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Research team identifies human ‘memory gene’

Researchers at the Translational Genomics Research Institute (TGen) today announced the discovery of a gene that plays a significant role in memory performance in humans. The findings, reported by TGen and research colleagues at the University of Zurich in Switzerland, Banner Alzheimer’s Institute, and Mayo Clinic Scottsdale, appear in the October 20 issue of Science. The study details how researchers associated memory performance with a gene called Kibra in over 1,000 individuals –both young and old– from Switzerland and Arizona. This study is the first to describe scanning the human genetic blueprint at over 500,000 positions to identify cognitive differences between humans.
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Jumping gene could provide non-viral alternative for gene therapy

A jumping gene first identified in a cabbage-eating moth may one day provide a safer, target-specific alternative to viruses for gene therapy, researchers say.

They compared the ability of the four best-characterized jumping genes, or transposons, to insert themselves into a cell’s DNA and produce a desired change, such as making the cell resistant to damage from radiation therapy.

They found the piggyBac transposon was five to 10 times better than the other circular pieces of DNA at making a home and a difference in several mammalian cell lines, including three human ones.
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Genome code cracked for breast and colon cancers

Scientists have completed the first draft of the genetic code for breast and colon cancers. Their report, published online in the September 7 issue of Science Express, identifies close to 200 mutated genes, now linked to these cancers, most of which were not previously recognized as associated with tumor initiation, growth, spread or control.

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Researchers identify gene as protector of DNA, enemy of tumors

A single gene plays a pivotal role launching two DNA damage detection and repair pathways in the human genome, suggesting that it functions as a previously unidentified tumor suppressor gene, researchers at The University of Texas M. D. Anderson Cancer Center report in Cancer Cell.

The advance online publication also reports that the gene – called BRIT1 – is under-expressed in human ovarian, breast and prostate cancer cell lines.
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Human embryonic stem cells display a unique pattern of chemical modification to DNA

Scientists have found that the DNA of human embryonic stem cells is chemically modified in a characteristic, predictable pattern. This pattern distinguishes human embryonic stem cells from normal adult cells and cell lines, including cancer cells. The study, which appears online today in Genome Research, should help researchers understand how epigenetic factors contribute to self-renewal and developmental pluripotence, unique characteristics of human embryonic stem cells that may one day allow them to be used to replace diseased or damaged cells with healthy ones in a process called therapeutic cloning.
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Scientists Discover a Genetic Code for Organizing DNA

DNA – the long, thin molecule that carries our hereditary material – is compressed around protein scaffolding in the cell nucleus into tiny spheres called nucleosomes. The bead-like nucleosomes are strung along the entire chromosome, which is itself folded and packaged to fit into the nucleus. What determines how, when and where a nucleosome will be positioned along the DNA sequence?

Dr. Eran Segal and research student Yair Field of the Computer Science and Applied Mathematics Department at the Weizmann Institute of Science have succeeded, together with colleagues from Northwestern University in Chicago, in cracking the genetic code that sets the rules for where on the DNA strand the nucleosomes will be situated. Their findings appeared today in Nature.
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Speeding discovery of the ‘human cancer genome’

Two gene discoveries announced in separate reports in the June 30, 2006 issue of Cell highlight one way to speed through the human genome in search of those genes most important for spawning cancer. Both groups say that a critical element in the enterprise to efficiently characterize the “human cancer genome” –a comprehensive collection of the genetic alterations responsible for major cancers–is the strategic comparison of human tumors with those of mice.

As a demonstration of the value of such strategic comparisons between species, the researchers report promising finds: one of the research teams identified two genes that can–in some circumstances–conspire to produce liver cancer, while the second uncovered a gene important to the spread of melanoma, the most serious form of skin cancer. Such functionally important genes, and the larger genetic pathways of which they are a part, are also those with the most promise as potential targets for cancer drugs, according to the researchers.
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Cells use mix-and-match approach to tailor regulation of genes

Scientists eager to help develop a new generation of pharmaceuticals are studying cellular proteins called transcription factors, which bind to upstream sequences of genes to turn the expression of those genes on or off. Some pharmaceutical companies are also hoping to develop drugs that selectively block the binding of transcription factors as a way to short-circuit the harmful effects of diseases.

Bioengineering researchers at UCSD and two research institutes in Germany report in the June 16 issue of PLoS Computational Biology that transcription factors act not only in isolation, but also in pairs, trios, and combinations of up to 13 to regulate distinct sets of genes.

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Scientists publishes first human microbiome analysis

For the first time, scientists have defined the collective genome of the human gut, or colon. Up to 100 trillion microbes, representing more than 1,000 species, make up a motley "microbiome" that allows humans to digest much of what we eat, including some vitamins, sugars, and fiber, an accomplishment that has far-reaching implications for clinical diagnosis and treatment of many human diseases.

In a study published in the June 2 issue of Science, scientists at The Institute for Genomic Research (TIGR) and their colleagues describe and analyze the colon microbiome, which includes more than 60,000 genes–twice as many as found in the human genome. Some of these microbial genes code for enzymes that humans need to digest food, suggesting that bacteria in the colon co-evolved with their human host, to mutual benefit.

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Researchers Create New ‘Matchmaking Service’ Computer System To Study Gene Interactions

Biologists in recent years have identified every individual gene in the genomes of several organisms. While this has been quite an accomplishment in itself, the further goal of figuring out how these genes interact is truly daunting.

The difficulty lies in the fact that two genes can pair up in a gigantic number of ways. If an organism has a genome of 20,000 genes, for example, the total number of pairwise combinations is a staggering total of 200 million possible interactions.

Researchers can indeed perform experiments to see what happens when the two genes interact, but 200 million is an enormous number of experiments, says Weiwei Zhong, a postdoctoral scholar at the California Institute of Technology. “The question is whether we can prioritize which experiments we should do in order to save a lot of time.”

To get at this issue, Zhong and her supervising professor, Paul Sternberg, have derived a method of database-mining to make predictions about genetic interactions. In the current issue of the journal Science, they report on a procedure for computationally integrating several sources of data from several organisms to study the tiny worm C. elegans, or nematode, an animal commonly used in biological experiments.
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Tiny RNA molecules fine-tune the brain’s synapses

Non-coding regions of the genome – those that don’t code for proteins – are now known to include important elements that regulate gene activity. Among those elements are microRNAs, tiny, recently discovered RNA molecules that suppress gene expression. Increasing evidence indicates a role for microRNAs in the developing nervous system, and researchers from Children’s Hospital Boston now demonstrate that one microRNA affects the development of synapses – the points of communication between brain cells that underlie learning and memory.

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A method is developed to silence genes in specific tissues using RNAi

Researchers at The University of Texas M. D. Anderson Cancer Center say they have jumped a significant hurdle in the use of RNA interference (RNAi), believed by many to be the ultimate tool to both decode the function of individual genes in the human genome and to treat disease.

Reporting in the journal Genes and Development, investigators have developed a simple way to use the RNAi approach to silence a selected gene in a specific tissue in a mouse to determine the function of that targeted gene.

This is another major breakthrough related to RNA interferene that was the topic of my prior post.
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First synthetic biology company is launched

Synthetic Genomics, Inc., a company founded by the genome sequencing pioneer Dr. J. Craig Venter, is developing new scientific processes to enable industry to design and test desired genetic modifications. Using the genome as a bio-factory, a custom designed, modular “cassette” system will be developed so that the organism executes specific molecular functions. Synthetically produced organisms with reduced or reoriented metabolic needs will enable new, powerful, and more direct methods of bio-engineered industrial production.

According to Dr. Venter: “Work in creating a synthetic chromosome/genome will give us a better understanding of basic cellular processes. Genome composition, regulatory circuits, signaling pathways and numerous other aspects of organism gene and protein function will be better understood through construction of a synthetic genome. Not only will this basic research lead to better understanding of these pathways and components in the particular organisms, but also better understanding of human biology. The ability to construct synthetic genomes may lead to extraordinary advances in our ability to engineer microorganisms for many vital energy and environmental purposes.”

This is a very exciting new step towards biosingularity. Dr. Venter is a true visionary who has been relentlessly pushing the technology to decode the complex program of biological systems.
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Decoding The Genome of a Fungus May Help Combat Disease And Lead To New Drugs

An international consortium of researchers led by the University of Manchester has cracked the gene code behind a key family of fungi, which includes both the leading cause of death in leukaemia and bone marrow transplant patients and an essential ingredient of soy sauce.

The ‘genome sequences’ or genetic maps for the fungi Aspergillus fumigatus, Aspergillus nidulans and Aspergillus oryzae are published on 22 December in Nature magazine. Despite being from the same fungal family, they have been found to be as genetically different as fish and man.

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Cleistothecium – sexual spore container, false coloured from Aspergillus nidulans. (Courtesy of Professor Rheinhard Fischer, Institut für Angewandte Biowissenschaften Abt. für Angewandte Mikrobiologie der Universität Karlsruh, with whom copyright remains)

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How E. coli bacterium generates simplicity from complexity

The ubiquitous and usually harmless E. coli bacterium, which has one-seventh the number of genes as a human, has more than 1,000 of them involved in metabolism and metabolic regulation. Activation of random combinations of these genes would theoretically be capable of generating a huge variety of internal states; however, researchers at UCSD will report in the Dec. 27 issue of Proceedings of the National Academy of Sciences (PNAS) that Escherichia coli doesn’t gamble with its metabolism. In a surprise about E. coli that may offer clues about how human cells operate, the PNAS paper reports that only a handful of dominant metabolic states are found in E. coli when it is “grown” in 15,580 different environments in computer simulations.
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Creating first synthetic life form

Work on the world’s first human-made species is well under way at a research complex in Rockville, Md., and scientists in Canada have been quietly conducting experiments to help bring such a creature to life.

Robert Holt, head of sequencing for the Genome Science Centre at the University of British Columbia, is leading efforts at his Vancouver lab to play a key role in the production of the first synthetic life form — a microbe made from scratch.

The project is being spearheaded by U.S. scientist Craig Venter, who gained fame in his former job as head of Celera Genomics, which completed a privately-owned map of the human genome in 2000.
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Scientists Resurrect Woolly Mammoth DNA

Scientists have finally managed to take an extensive look at the genetic makeup of one of the most famous beasts of the last ice age. This week, an international team of researchers reports using a new technology to sequence a staggering 13 million basepairs of both nuclear and mitochondrial DNA from a 27,000-year-old frozen Siberian mammoth. Also this week, another team reports using a souped-up version of more conventional methods to sequence a mammoth’s entire mitochondrial genome.

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Science’s Breakthrough of the Year: Watching evolution in action

Evolution has been the foundation and guiding theory of biology since Darwin gave the theory its proper scientific debut in 1859. But Darwin probably never dreamed that researchers in 2005 would still be uncovering new details about the nuts and bolts of his theory — how does evolution actually work in the world of influenza genes and chimpanzee genes and stickleback fish armor? Studies that follow evolution in action claim top honors as the Breakthrough of the Year, named by Science and its publisher AAAS, the nonprofit science society.
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Microbe produces H2 from water, carbon monoxide

Take a pot of scalding water, remove all the oxygen, mix in a bit of poisonous carbon monoxide, and add a pinch of hydrogen gas. It sounds like a recipe for a witch’s brew. It may be, but it is also the preferred environment for a microbe known as Carboxydothermus hydrogenoformans.

In a paper published in the November 27th issue of PLoS Genetics, a research team led by scientists at The Institute for Genomic Research (TIGR) report the determination and analysis of the complete genome sequence of this organism. Isolated from a hot spring on the Russian volcanic island of Kunashir, this microbe lives almost entirely on carbon monoxide. While consuming this normally poisonous gas, the microbe mixes it with water, producing hydrogen gas as waste.
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